Olav Dalgard

• Opheim, Eirik; Malme, Kristian Nødtvedt; Dalgard, Olav; Rykkvin, Rikard; Backe, Øystein & Foshaug, Tarjei [Show all 8 contributors for this article] (2026). Prevalence of blood-borne viral infections and HBV vaccination coverage among people with recent injecting drug use in Oslo, 2002–2024. International journal of drug policy. ISSN 0955-3959. 157, p. 105502–105502. doi: 10.1016/j.drugpo.2026.105502. Full text in Research Archive
• Hovind, Magrit Jarlsdatter; Berdal, Jan-Erik; Benth, Jurate Saltyte; Dalgard, Olav & Lyngbakken, Magnus Nakrem (2026). Antibiotic therapy in viral airway infections (ATHENIAN): study protocol for an open labeled randomized controlled pragmatic trial to evaluate the efficacy and safety of discontinuing antibiotic therapy in adult patients infected with respiratory viruses. Trials. 27(1). doi: 10.1186/s13063-026-09730-3. Full text in Research Archive Show summary

  Background Reducing inappropriate use of antibiotics is essential to combat antimicrobial resistance. Antibiotics are widely prescribed upon hospital admission for acute respiratory infections, but it remains unknown whether it is safe to discontinue antibiotics when a respiratory virus is detected in these patients. With this randomized trial, we aim to assess the efficacy and safety of discontinuing antibiotic therapy in patients admitted to the hospital with a polymerase chain reaction test positive for respiratory virus and no clear evidence of bacterial infection. Methods ATHENIAN is an ongoing multicenter, open-label, pragmatic, randomized non-inferiority trial. We aim to recruit 400 adult patients initiated on antibiotic therapy at admittance to one of the 10 study sites in Norway and with a positive polymerase chain reaction test for influenza virus, human metapneumovirus, respiratory syncytial virus, or parainfluenza virus. The participants are randomized to intervention, discontinuation of antibiotic therapy, or control, continuation of antibiotic therapy at the discretion of the treating physician. We hypothesize that discontinuation of antibiotic therapy is safe and non-inferior to continuation of antibiotic therapy. The primary outcome, assessed at 120 h after randomization, is early clinical response, defined as survival with symptom improvement without receipt of rescue antibacterial therapy. Secondary outcomes include all-cause in-hospital and 30-day mortality, duration of hospital admission, days of therapy with antibiotics, rescue antibiotic therapy during hospital admission, new antibiotic therapy for presumed airway infection up to 30 days after hospital discharge, and hospital readmissions within 30 days after hospital discharge. Discussion To our knowledge, ATHENIAN is the first randomized controlled trial assessing the safety and efficacy of antimicrobial de-escalation based on multiplex nucleic acid amplification test results. Addressing this knowledge gap using a pragmatic study design will provide valuable insights that may influence treatment algorithms and antibiotic prescription practices. The study has the potential to contribute to a reduction in the inappropriate use of antibiotics and the emergence of antimicrobial resistance. Trial registration ClinicalTrials.gov NCT05045612. Registered on September 7, 2021.

• Opheim, Eirik; Fredriksen, Anette; Hauge, Joakim; Dalgard, Olav; Malme, Kristian Nødtvedt & Midgard, Håvard (2026). Hepatitis C treatment uptake among incarcerated people in Norway, 2018–2019. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. p. 1–9. doi: 10.1080/00365521.2026.2685826. Full text in Research Archive Show summary

  Introduction: Chronic hepatitis C virus (HCV) infection is common among imprisoned people. We aimed to assess HCV treatment uptake and associated factors before and after imprisonment among incarcerated individuals with chronic HCV infection. Methods: Newly incarcerated individuals in six Norwegian prisons were consecutively included in 2018-2019 and tested for HCV infection. The cohort was linked to national registries for HCV notification status and treatment dispensations. Treatment initiation was defined as dispensation of ≥1 pack (28 days) of HCV treatment. Results: Among 110 individuals with previous or current chronic HCV infection, the median age was 37 years, 79.1% male and 97.2% had ever injected drugs. Chronic HCV infection had been diagnosed in 88 persons before incarceration, of whom 34 (38.6%; 95% CI 28.4-49.6) had already initiated treatment. Among 76 with detectable HCV RNA at inclusion, 62 (81.6%; 95% CI 71.0-89.5) received treatment after incarceration, with a median time to treatment of 5.1 months. Treatment rates increased from 10.6/100 PY (95% CI 7.4-14.9) in the period before incarceration to 79.4/100 PY (95% CI 60.9-101.8) after incarceration. Following incarceration, time to treatment was shorter among individuals with sentence length ≥3 months than among those on remand or with shorter sentences (aHR 1.93; 95% CI 1.10-3.41; p < 0.001). Treatment completion was observed in 57 of 62 (91.9%) participants who initiated treatment after incarceration. Conclusion: HCV treatment uptake following incarceration was high, particularly among those with long sentences. HCV testing in prison should be followed by immediate treatment initiation, regardless of incarceration status and sentence length.

• Neumann, Kirill; Hovind, Magrit Jarlsdatter; Berdal, Jan-Erik; Dalgard, Olav; Leegaard, Truls Michael & Siljan, William Ward [Show all 8 contributors for this article] (2026). Acute Respiratory Failure and Ventilatory Support in Hospitalized Adults With Viral Respiratory Infection: A Retrospective Cohort Study. Open Forum Infectious Diseases. 13(4). doi: 10.1093/ofid/ofag189. Full text in Research Archive
• Hovind, Magrit Jarlsdatter; Berdal, Jan-Erik; Dalgard, Olav & Lyngbakken, Magnus Nakrem (2026). A comparison of clinical characteristics and mortality in hospitalised patients with respiratory syncytial virus and influenza virus infections: a cohort study. Infectious Diseases. ISSN 2374-4235. doi: 10.1080/23744235.2026.2621994. Full text in Research Archive
• Holmberg, Marte; Niehrs, Annika; Dalgard, Olav; Berhe, Nega; Desalegn, Hailemichael & Aleman, Soo [Show all 20 contributors for this article] (2026). Hepatic flares, their immune signatures, and ALT variability after nucleos(t)ide analogue cessation in HBeAg-negative hepatitis B. JHEP Reports. doi: 10.1016/j.jhepr.2026.101875. Full text in Research Archive Show summary

  Background and aims: Hepatic flares frequently occur after nucleos(t)ide analogue (NA) cessation in patients with chronic hepatitis B (CHB) and can be beneficial ("good flares") or harmful ("bad flares"). We characterised flares after NA cessation aiming to identify predictors and immunological correlates of good and bad flares. Methods: This study was nested in the prospective Nuc-Stop study, in which 127 patients with e-antigen negative CHB discontinued NA treatment with a 36-month follow-up. Flares were defined as an ALT increase >2× the upper limit of normal or >2× baseline. Predictors of flares were identified by logistic regression. In 32 patients with flares without treatment restart, we compared clinical characteristics and soluble immune marker profiles of good flares (hepatitis B surface antigen (HBsAg) loss or >1 log10 decline or sustained virological control) and bad flares (neither HBsAg decline nor virological control). Results: Flares occurred in 58.3% of patients. Age (per 1-year increment; adjusted odds ratio (aOR), 1.07; 95% confidence interval (CI) 1.02-1.12) and end-of-treatment HBsAg level (per 1 log10 IU/mL increment; aOR, 2.09; 95% CI 1.20-3.62) independently predicted flares. Good flares displayed less ALT variability after the initial spike than bad flares (standard deviation 9.7 vs. 22.7 U/L, p=0.002). Analysis of soluble immune markers confirmed distinct clusters for good and bad flares at end-of-treatment, with higher serum levels of specific proteins in good flares (e.g. IL-13, TRAIL) and bad flares (e.g. CXCL11, OPG, TNF). Conclusions: Flares occurred in over half the patients after NA cessation and were associated with age and end-of-treatment HBsAg levels. ALT variability following the initial flare and soluble marker profiles might serve as prognostic factors and distinguish good from bad flares. Impact and implications: Nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B may facilitate functional cure, but hepatic flares are common and potentially detrimental, making careful patient selection essential. In this prospective, multicentre trial, flares occurred in over half of the patients, with severe flares in 12.6%. Increasing age and higher end-of-treatment HBsAg levels were predictors of flares and should be considered when deciding on treatment discontinuation. Close monitoring, particularly during the first six months, is critical for safe patient management, while ALT variability following the initial flare and soluble immune markers may help differentiate good from bad flares and guide retreatment decisions.

• Hauge, J.; Kielland, Knut Boe; Opheim, Eirik; Jarnæss, Elisabeth; Midgard, Håvard & Dalgard, Olav (2026). Hepatitis C infection among people incarcerated in Norwegian prisons. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. doi: 10.1080/00365521.2026.2624019. Full text in Research Archive
• Pihl, Charlotte Meinich; Malme, Kristian Nødtvedt; Ulstein, K.; Hauge, J.; Backe, Ø. & Foshaug, T. [Show all 8 contributors for this article] (2026). All-cause and liver-related mortality among people who inject drugs with chronic hepatitis C virus infection in Oslo, Norway. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. p. 1–9. doi: 10.1080/00365521.2026.2636072. Full text in Research Archive
• Massonnaud, Clément R.; Peiffer-Smadja, Nathan; Poignard, Pascal; Jamard, Simon; Goehringer, François & Danion, François [Show all 85 contributors for this article] (2025). Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in patients hospitalized with COVID-19: long-term results from the DisCoVeRy trial. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 32(4), p. 618–628. doi: 10.1016/j.cmi.2025.12.014. Full text in Research Archive
• Opheim, Eirik; Malme, Kristian Nødtvedt; Dalgard, Olav; Sørli, Hanne; Backe, Øystein & Foshaug, Tarjei [Show all 16 contributors for this article] (2025). Changes in Risk Behaviour Among People With Recent Injecting Drug Use in Oslo 2002–2024. Drug and Alcohol Review. ISSN 0959-5236. 45(1). doi: 10.1111/dar.70060. Full text in Research Archive
• Gahrton, Caroline; Kåberg, Martin; Lybeck, Charlotte; Lindahl, Karin; Patil, Snehal & Dalgard, Olav [Show all 8 contributors for this article] (2025). Treatment uptake among individuals notified with HCV infection 1990–2022 in Sweden. Infectious Diseases. ISSN 2374-4235. 58(3), p. 279–289. doi: 10.1080/23744235.2025.2569504. Full text in Research Archive
• Hovind, Magrit Jarlsdatter; Berdal, Jan-Erik; Dalgard, Olav & Lyngbakken, Magnus Nakrem (2025). Empiric Antibiotic Therapy in Suspected Sepsis: Impact of Gentamicin-Based Regimens on Incident Renal Failure and Mortality. Open Forum Infectious Diseases. 12(6). doi: 10.1093/ofid/ofaf319. Full text in Research Archive Show summary

  Background The efficacy and safety of administering a narrow-spectrum β-lactam and gentamicin as empirical therapy for community-acquired sepsis has been questioned. We compared the efficacy and safety of this combination with that of broad-spectrum β-lactams (cefotaxime, piperacillin-tazobactam, or meropenem) in patients with suspected sepsis. Methods In this retrospective study, we included patients initiated on narrow-spectrum β-lactam/gentamicin or broad-spectrum β-lactams for suspected sepsis between January 2017 and December 2022. Patients without baseline creatinine and at least 1 subsequent creatinine measurement were excluded. We compared the impact of antibiotic regimens using a 5-level ordinal outcome scale ranging from no acute kidney injury (AKI) to all-cause death during 30-day follow-up. Results Among 1917 patients, 33.1% received narrow-spectrum β-lactam/gentamicin, and 66.9% received broad-spectrum β-lactams. Patients initiated on broad-spectrum β-lactams had more comorbidities, had lower estimated glomerular filtration rate on admission, and more frequently required treatment with noradrenaline, respiratory support, and admission to the intensive care and medical intermediate care units. Therapy with broad-spectrum β-lactams was associated with a higher posttreatment stage of AKI or death (adjusted odds ratio, 1.61 [95% confidence interval, 1.27–2.04]). We found no significant association between cumulative dose of gentamicin and peak creatinine value. For patients treated with gentamicin experiencing AKI, creatinine normalized during 30-day follow-up. Conclusions In patients with suspected sepsis, empirical treatment with narrow-spectrum β-lactam/gentamicin was not associated with an increased risk of AKI or death. If local antimicrobial resistance patterns permit, narrow-spectrum β-lactam/gentamicin may reduce broad-spectrum β-lactam usage, addressing a key element of antibiotic stewardship.

• Salamanca, Beatriz Valcarcel; Johannessen, Asgeir; Dalgard, Olav & Whittaker, Robert Neil (2025). Linkage to Care, Retention in Care and Treatment Uptake Among Patients Diagnosed With Chronic Hepatitis B in Norway, 2008–2022. Journal of Viral Hepatitis. ISSN 1352-0504. 32(10), p. 1–11. doi: 10.1111/jvh.70089. Full text in Research Archive Show summary

  ABSTRACT People living with chronic hepatitis B infection (PLWHB) need life‐long care to monitor liver health and treatment need. Data on clinical follow‐up for PLWHB are essential to monitor the health system response to this infection. We used linked national registry data to calculate the proportion of diagnosed PLWHB in Norway linked to specialist care (LTC), treated and retained in specialist or primary care (RIC) from 2008 to 2022. We described the outcomes by time, age, sex, region of residence, place of birth and residence status. Using log‐binomial regression, we explored how these factors were associated with ever being LTC and being RIC during the last 12 months of the study period. Among 10,542 diagnosed PLWHB, 8301 (79%) had ever been LTC and 2454 (23%) had received treatment. In the first 2 years after LTC, 64% were still RIC. At the end of the study period, 4476 (50%) of 8979 PLWHB still resident in Norway had been RIC in the last 12 months. PLWHB born outside Norway had a higher probability of LTC (relative risk [RR]: 1.24; 95% confidence interval [CI] 1.19–1.29) and RIC (RR: 1.67; 95% CI 1.53–1.84). Other significant associations with smaller effect sizes included a higher probability of LTC among PLWHB aged < 25 years and a lower probability of RIC when diagnosed from 2010 to 2013 or aged ≥ 65 years. The management of diagnosed PLWHB in Norway is suboptimal. Our study provides a framework for how key performance indicators can be monitored in ongoing national surveillance.

• Salamanca, Beatriz Valcarcel; Johannessen, Asgeir; Dalgard, Olav; Finbråten, Ane-Kristine & Whittaker, Robert Neil (2025). Time from migration to diagnosis and the proportion presenting late among diagnosed cases of chronic hepatitis B in Norway, 2008 to 2022. Infectious Diseases. ISSN 2374-4235. 57(12), p. 1105–1116. doi: 10.1080/23744235.2025.2530203. Full text in Research Archive
• Razavi, Homie A.; Waked, Imam; Qureshi, Huma; Kondili, Loreta A.; Duberg, Ann-Sofi & Aleman, Soo [Show all 50 contributors for this article] (2025). Number of people treated for hepatitis C virus infection in 2014-2023 and applicable lessons for new HBV and HDV therapies. Journal of Hepatology. ISSN 0168-8278. 83(2), p. 329–347. doi: 10.1016/j.jhep.2025.01.013. Full text in Research Archive Show summary

  Background and aims: The year 2023 marked the 10-year anniversary of the launch of direct-acting antivirals (DAAs) for the treatment of the hepatitis C virus (HCV). HCV treatment trends by country, region, and globally are important to monitor progress toward the World Health Organization's 2030 elimination targets. Additionally, the historical patterns can help predict the treatment uptake for future therapies for other liver diseases. Methods: The number of people living with HCV (PLHCV) treated between 2014-2023 across 119 countries was estimated using national HCV registries, reported DAA sales data, pharmaceutical companies' reports, and estimates provided by national experts. For the countries with no available data, the average estimate of the corresponding Global Burden of Disease region was used. Results: An estimated 13,816,000 (95% uncertainty intervals (UI): 13,221,000-16,415,000) PLHCV were treated, of whom 12,748,000 (12,226,000-15,231,000) were treated with DAAs, of which 11,081,000 (10,542,000-13,338,000) were sofosbuvir-based DAA regimens. Country-level data accounted for 97% of these estimates. In high-income countries, there was a 41% drop in treatment from its peak, and reimbursement was a large predictor of treatment. In low- and middle-income countries, price played an important role in expanding treatment access through the public and private markets, and treatment continues to increase slowly after a sharp drop at the end of the Egyptian national program. Conclusions: In the last 10 years, 21% of all HCV infections were treated with DAAs. Regional and temporal variations highlight the importance of active screening strategies. Without program enhancements, the number of treated PLHCV stalled in every country/region which may not reflect a lower prevalence but may instead reflect the diminishing returns of the existing strategies. Impact and implications: Long-term hepatitis C virus (HCV) infection can lead to cirrhosis and liver cancer. Since 2014, these infections can be effectively treated with 8-12 weeks of oral therapies. In 2015, the World Health Organization (WHO) established targets to eliminate HCV by 2030, which included treatment targets for member countries. The current study examines HCV treatment patterns across 119 countries and regions from 2014 to 2023 to assess the impact of national programs. This study can assist physicians and policymakers in understanding treatment patterns within similar regions or income groups and in utilizing historical data to refine their strategies in the future.

• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Show all 73 contributors for this article] (2024). High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 296(3), p. 249–259. doi: 10.1111/joim.13820. Full text in Research Archive Show summary

  Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

• Viermyr, Hans-Kittil; Tonby, Kristian; Ponzi, Erica; Trouillet-Assant, Sophie; Poissy, Julien & Arribas, José R. [Show all 49 contributors for this article] (2024). Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial. EBioMedicine. 111. doi: 10.1016/j.ebiom.2024.105511. Full text in Research Archive Show summary

  Background The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19. Methods Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status. Findings Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs. Interpretation This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size.

• Whittaker, Robert Neil; Midgard, Håvard; Dalgard, Olav & Kløvstad, Hilde (2024). Treatment uptake among notified cases of hepatitis C virus infection in Norway, 1990 to 2022: a registry-based study to monitor progress towards elimination. Eurosurveillance. ISSN 1025-496X. 29(46). doi: 10.2807/1560-7917.ES.2024.29.46.2400180. Full text in Research Archive Show summary

  Background Hepatitis C virus (HCV) infection is targeted for elimination as a public health threat by 2030. The World Health Organization goal for treatment uptake is ≥ 80% among cases diagnosed with an active HCV infection (RNA- or core antigen-positive), maintained for 2 years. Aim To calculate treatment uptake, time from diagnosis to treatment start and complete treatment dispensation among notified cases of HCV infection in Norway. Method We linked national data on notified cases diagnosed from 1990–2022 to dispensed prescriptions for HCV treatment from January 2004–February 2023 and data on residence status at the end of 2022. We described treatment uptake by demographic and epidemiological characteristics. We calculated the median number of months from diagnosis to treatment start by year. For direct-acting antiviral treatment periods, complete dispensation was based on the treatment and number of defined daily doses. Results Among 12,178 notified cases that had an active infection at diagnosis and were still resident, 10,091 (83%) had received treatment. Uptake among resident cases was > 80% in 2021 and 2022. The median number of months from diagnosis to treatment decreased over time to 3 (interquartile range: 1–5) among cases diagnosed in 2021 and 2022. From 2015–22, 89–93% of direct-acting antiviral treatment periods annually had complete treatment dispensed. Conclusion Norway has achieved the elimination goal for treatment uptake among notified cases diagnosed with an active HCV infection. This highlights the benefit of a strategy that includes unrestricted, simplified and integrated treatment options.

• Druckrey-Fiskaaen, Karl Trygve; Vold, Jørn Henrik; Madebo, Tesfaye; Midgard, Håvard; Dalgard, Olav & Leiva, Rafael Alexander Mo [Show all 7 contributors for this article] (2024). Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study. Substance Abuse Treatment, Prevention, and Policy. 19(1). doi: 10.1186/s13011-024-00603-z. Full text in Research Archive Show summary

  Background: Persons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances. Methods: Data was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI). Results: At baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement. Conclusions: More than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

• Hovind, Magrit Jarlsdatter; Berdal, Jan-Erik; Dalgard, Olav & Lyngbakken, Magnus Nakrem (2024). Impact of antibiotic therapy in patients with respiratory viral infections: a retrospective cohort study. Infectious Diseases. ISSN 2374-4235. 56(12), p. 1031–1039. doi: 10.1080/23744235.2024.2375592. Full text in Research Archive Show summary

  Objectives The impact of antibiotics in patients with positive polymerase chain reaction (PCR) for respiratory viruses without evidence of a respiratory bacterial co-infection is largely unknown. The aim of this study was to assess the association of antibiotics on 30-day mortality and length of hospital stay in patients with an acute respiratory infection and PCR documented presence of respiratory viruses. Methods We conducted a retrospective cohort study of adult patients admitted to hospital between 2012 and 2021 with positive PCR for influenza virus (H3N2, H1N1, influenza B), respiratory syncytial virus, human metapneumovirus or severe acute respiratory syndrome coronavirus 2. We used logistic regression, the Kaplan–Meier estimator and Poisson’s regression to assess the impact of antibiotic therapy on outcomes. Results Among 3979 patients, 67.7% received antibiotics. In adjusted analyses, antibiotics initiated in the emergency department (adjusted OR 1.23, 95% CI 0.77–1.96) and days of antibiotic therapy (adjusted OR per day of therapy 0.98, 95% CI 0.95–1.00) had no significant impact on mortality, whereas antibiotics initiated later during admission (adjusted OR 2.25, 95% CI 1.26–4.02) was associated with increased mortality. Patients prescribed antibiotics had longer duration of hospital admission. Conclusions We observed no protective association between in-hospital antibiotic therapy and outcomes, suggesting overuse of antibiotics in respiratory infections with proven respiratory viruses. A restrictive antibiotic strategy may be warranted.

• Gahrton, Caroline; Navér, Georg; Warnqvist, Anna; Dalgard, Olav; Aleman, Soo & Kåberg, Martin (2024). Changes in hepatitis C virus prevalence and incidence among people who inject drugs in the direct acting antiviral era. International journal of drug policy. ISSN 0955-3959. 128. doi: 10.1016/j.drugpo.2024.104433. Full text in Research Archive
• Johannessen, Asgeir; Reikvam, Dag Henrik; Aleman, Soo; Berhe, Nega; Weis, Nina & Mekonnen, Hailemichael Desalegn [Show all 24 contributors for this article] (2024). Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 60(4), p. 434–445. doi: 10.1111/apt.18147. Full text in Research Archive Show summary

  Background: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. Aim: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. Methods: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. Results: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. Conclusions: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

• Malme, Kristian Nødtvedt; Stene-Johansen, Kathrine; Klundby, Ingvild; Backe, Øystein; Foshaug, Tarjei & Greve, Maria Helseth [Show all 10 contributors for this article] (2024). Virologic Response and Reinfection Following HCV Treatment among Hospitalized People Who Inject Drugs: Follow-Up Data from the OPPORTUNI-C Trial. Viruses. 16(6). doi: 10.3390/v16060858. Full text in Research Archive Show summary

  Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50–70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46–66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08–2.22]; p = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3–37.8]; p < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0–9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.

• Razavi-Shearer, Devin M.; Gamkrelidze, Ivane; Pan, Calvin Q.; Jia, Jidong; Berg, Thomas & Gray, Richard T. [Show all 269 contributors for this article] (2023). Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 8(10), p. 879–907. doi: 10.1016/S2468-1253(23)00197-8. Full text in Research Archive
• Holmberg, Marte; Aass, Hans Christian; Dalgard, Olav; Samuelsen, Ellen; Sun, Dan & Björkström, Niklas K. [Show all 8 contributors for this article] (2023). Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines. Scientific Reports. 13(1). doi: 10.1038/s41598-023-50216-y. Full text in Research Archive Show summary

  Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.

• Trøseid, Marius; Arribas, José R.; Assoumou, Lambert; Holten, Aleksander Rygh; Poissy, Julien & Terzić, Vida [Show all 56 contributors for this article] (2023). Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial. Critical Care. ISSN 1364-8535. 27(9), p. 1–15. doi: 10.1186/s13054-022-04205-8. Full text in Research Archive Show summary

  Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies.

• Midgard, Håvard; Malme, Kristian Braathen; Phil, Charlotte Meinich; Berg-Pedersen, Riikka Mari; Tanum, Lars Håkon Reiestad & Klundby, Ingvild [Show all 12 contributors for this article] (2023). Opportunistic Treatment of Hepatitis C Infection Among Hospitalized People Who Inject Drugs (OPPORTUNI-C): A Stepped Wedge Cluster Randomized Trial. Clinical Infectious Diseases. ISSN 1058-4838. 78(3), p. 582–590. doi: 10.1093/cid/ciad711. Full text in Research Archive Show summary

  Background. We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID). Methods. We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment. Results. A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2–77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1–45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0–46.2]; risk ratio 1.9 [95% CI: 1.4–2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8–12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5–6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8–70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6–73.9]) during control conditions. Conclusions. An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation. Clinical Trials Registration. NCT04220645 Keywords. hepatitis C virus; people who inject drugs; model of care; pragmatic clinical trial; stepped wedge cluster randomized trial.

• Cheng, Qinglu; Cunningham, Evan B.; Shih, Sophy; Amin, Janaki; Bruneau, Julie & Artenie, Adelina A. [Show all 22 contributors for this article] (2023). Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs. Value in Health. ISSN 1098-3015. 26(6), p. 883–892. doi: 10.1016/j.jval.2022.12.016. Full text in Research Archive
• Opheim, Eirik; Dalgard, Olav; Ulstein, Kjersti Anne; Sørlie, Hanne; Backe, Øystein & Foshaug, Tarjei [Show all 8 contributors for this article] (2023). Towards elimination of hepatitis C in Oslo: Cross-sectional prevalence studies among people who inject drugs. International journal of drug policy. ISSN 0955-3959. 123. doi: 10.1016/j.drugpo.2023.104279. Full text in Research Archive
• Handal, Nina; Whitworth, Jimmy; Lyngbakken, Magnus Nakrem; Berdal, Jan-Erik; Dalgard, Olav & Jørgensen, Silje Bakken (2023). Mortality and length of hospital stay after bloodstream infections caused by ESBL-producing compared to non-ESBL-producing E. coli. Infectious Diseases. ISSN 2374-4235. 56(1), p. 19–31. doi: 10.1080/23744235.2023.2261538. Full text in Research Archive Show summary

  Objective To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups. Methods A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital. Results A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7–3.7, p = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin (n = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p < 0.001). No significant difference in the length of hospital stay was found for other sources of infection (n = 151), with a median of seven versus six days (p = 0.550) in the ESBL- and non-ESBL groups, respectively. Conclusion There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin.

• Malme, Kristian Nødtvedt; Ulstein, Kjersti Anne; Finbråten, Ane-Kristine; Wüsthoff, Linda Elise; Kielland, Knut Boe & Hauge, Joakim [Show all 8 contributors for this article] (2023). Hepatitis C treatment uptake among people who inject drugs in Oslo, Norway: A registry-based study. International journal of drug policy. ISSN 0955-3959. 116. doi: 10.1016/j.drugpo.2023.104044. Full text in Research Archive Show summary

  Background: Improving HCV treatment uptake among people who inject drugs (PWID) is crucial to achieving the WHO elimination targets. The aims were to evaluate HCV treatment uptake and HCV RNA prevalence in a large cohort of PWID in Norway. Methods: Registry-based observational study where all users of the City of Oslo's low-threshold social and health services for PWID between 2010-2016 (n = 5330) were linked to HCV notifications (1990-2019) and dispensions of HCV treatment, opioid agonist treatment (OAT) and benzodiazepines (2004-2019). Cases were weighted to account for spontaneous HCV clearance. Treatment rates were calculated using person-time of observation, and factors associated with treatment uptake were analysed using logistic regression. HCV RNA prevalence was estimated among individuals alive by the end of 2019. Results: Among 2436 participants with chronic HCV infection (mean age 46.8 years, 30.7% female, 73.3% OAT), 1118 (45.9%) had received HCV treatment between 2010-2019 (88.7% DAA-based). Treatment rates increased from 1.4/100 PY (95% CI 1.1-1.8) in the pre-DAA period (2010-2013) to 3.5/100 PY (95% CI 3.0-4.0) in the early DAA period (2014-2016; fibrosis restrictions) and 18.4/100 PY (95% CI 17.2-19.7) in the late DAA period (2017-2019; no restrictions). Treatment rates for 2018 and 2019 exceeded a previously modelled elimination threshold of 50/1000 PWID. Treatment uptake was less likely among women (aOR 0.74; 95% CI 0.62-0.89) and those aged 40-49 years (aOR 0.74; 95% CI 0.56-0.97), and more likely among participants with current OAT (aOR 1.21; 95% CI 1.01-1.45). The estimated HCV RNA prevalence by the end of 2019 was 23.6% (95% CI 22.3-24.9). Conclusion: Although HCV treatment uptake among PWID increased, strategies to improve treatment among women and individuals not engaged in OAT should be addressed.

• Grebely, Jason; Robaeys, Geert; Bruggmann, Philip; Aghemo, Alessio; Backmund, Markus & Bruneau, Julie [Show all 20 contributors for this article] (2023). Empfehlungen zur Hepatitis Versorgung bei Drogenkonsumierenden. International journal of drug policy. ISSN 0955-3959. 111, p. 101670–101670. doi: 10.1016/j.drugpo.2015.11.010. Full text in Research Archive
• Dalgard, Olav; Litwin, Alain H.; Shibolet, Oren; Grebely, Jason; Nahass, Ronald & Altice, Frederick L. [Show all 16 contributors for this article] (2022). Health-related quality of life in people receiving opioid agonist treatment and treatment for hepatitis C virus infection. Journal of Addictive Diseases. ISSN 1055-0887. doi: 10.1080/10550887.2022.2088978. Full text in Research Archive Show summary

  Background In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). Objective To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection Methods COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. Results Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37–10.63), vitality (MTD, 6.81; 95% CI, 1.88–11.75), and mental health (MTD, 5.17; 95% CI, 0.52–9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29–5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. Conclusion HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL.

• Pan, Hongchao; Peto, Richard; Karim, Quarraisha Abdool; Alejandria, Marissa M.; Henao-Restrepo, Ana-Maria & Hernández-García, César [Show all 51 contributors for this article] (2022). Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. The Lancet. ISSN 0140-6736. 399(10339), p. 1941–1953. doi: 10.1016/S0140-6736(22)00519-0. Full text in Research Archive Show summary

  Background The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. Methods Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. Findings Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. Interpretation Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).

• Leiva, Rafael Alexander Mo; Bergersen, Bente Magny; Finbråten, Ane-Kristine; Sandvei, Per; Simonsen, Øystein Tunheim & Rosseland, Carola Maria [Show all 13 contributors for this article] (2022). High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. doi: 10.1080/00365521.2022.2118555. Full text in Research Archive Show summary

  Background and aims The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. Method This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). Results We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. Conclusion We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing.

• Grebely, Jason; Dore, Gregory J.; Altice, Frederick L.; Conway, Brian; Litwin, Alain H. & Norton, Brianna L. [Show all 21 contributors for this article] (2022). Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy : A Cohort Study. Annals of Internal Medicine. ISSN 0003-4819. 175(9), p. 1221–1229. doi: 10.7326/M21-4119. Full text in Research Archive
• Chalabianloo, Fatemeh; Høiseth, Gudrun; Vold, Jørn Henrik; Johansson, Kjell Arne; Kringen, Marianne K. & Dalgard, Olav [Show all 12 contributors for this article] (2022). Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations. Journal of Addictive Diseases. ISSN 1055-0887. 41(1). doi: 10.1080/10550887.2022.2057140. Full text in Research Archive Show summary

  Background: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. Objectives: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. Methods: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016–2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. Results: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: −2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (−0.50; −4.59, 3.59; 0.810). Conclusions: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.

• Midgard, Håvard; Bjørnestad, Ronny; Egeland, Maren; Dahl, Eivin; Finbråten, Ane-Kristine & Kielland, Knut Boe [Show all 8 contributors for this article] (2022). Peer support in small towns: A decentralized mobile Hepatitis C virus clinic for people who inject drugs. Liver international (Print). ISSN 1478-3223. 42(6), p. 1268–1277. doi: 10.1111/liv.15266. Full text in Research Archive Show summary

  Background & aims: New models of HCV care are needed to reach people who inject drugs (PWID). The primary aim was to evaluate HCV treatment uptake among HCV RNA positive individuals identified by point-of-care (POC) testing and liver disease assessment in a peer-driven decentralized mobile clinic. Methods: This prospective study included consecutive patients assessed in a mobile clinic visiting 32 small towns in Southern Norway from November 2019 to November 2020. The clinic was staffed by a bus driver and a social educator offering POC HCV RNA testing (GeneXpert®), liver disease staging (FibroScan® 402) and peer support. Viremic individuals were offered prompt pan-genotypic treatment prescribed by local hospital-employed specialists following a brief telephone assessment. Results: Among 296 tested individuals, 102 (34%) were HCV RNA positive (median age 51 years, 77% male, 24% advanced liver fibrosis/cirrhosis). All participants had a history of injecting drug use, 71% reported past 3 months injecting, and 37% received opioid agonist treatment. Treatment uptake within 6 months following enrolment was achieved in 88%. Treatment uptake was negatively associated with recent injecting (aHR 0.60; 95% CI 0.36-0.98), harmful alcohol consumption (aHR 0.44; 95% CI 0.20-0.99), and advanced liver fibrosis/cirrhosis (aHR 0.44; 95% CI 0.25-0.80). HCV RNA prevalence increased with age (OR 1.81 per 10-year increase; 95% 1.41-2.32), ranging from 3% among those <30 years to 55% among those ≥60 years. Conclusions: A peer-driven mobile HCV clinic is an effective and feasible model of care that should be considered for broader implementation to reach PWID outside the urban centres. Keywords: hepatitis C virus; peer support; people who inject drugs; point of care; treatment. © 2022 The Authors. Liver International published by John Wiley & Sons Ltd.

• Kåsine, Trine; Riise, Anne Margarita Dyrhol; Barratt-Due, Andreas; Kildal, Anders Benjamin; Olsen, Inge Christoffer & Nezvalova-Henriksen, Katerina [Show all 39 contributors for this article] (2021). Neutrophil count predicts outcome in hospitalized COVID-19 patients. Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 291(2), p. 241–243. doi: 10.1111/joim.13377. Full text in Research Archive Show summary

  Despite numerous studies on SARS-CoV-2-induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure(RF). Few studies have evaluated the prognostic value of routine diagnostic repertoire available at most hospitals. The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial, evaluating hydroxychloroquine (HCQ)and remdesivir compared to standard of care in hospitalized COVID-19 patients [1]. We explored whether standard biomarkers in peripheral blood could give information on ICU admission and RFin hospitalized COVID-19 patients.

• Busschots, Dana; Bielen, Rob; Koc, Özgür M.; Heyens, Leen; Verrando, Rita & Galocsy, Chantal de [Show all 11 contributors for this article] (2021). Hepatitis C reinfection in former and active injecting drug users in Belgium. Harm Reduction Journal. 18(1), p. 1–7. doi: 10.1186/s12954-021-00552-x. Full text in Research Archive
• Duffell, Erika; Cortez-Pinto, Helena; Simonova, Marieta; Dalgard, Olav; Dahl, Elin Hoffmann & Martel, Catherine de [Show all 13 contributors for this article] (2021). Estimating the attributable fraction of cirrhosis and hepatocellular carcinoma due to hepatitis B and C. Journal of Viral Hepatitis. ISSN 1352-0504. 28(8), p. 1177–1189. doi: 10.1111/jvh.13545. Full text in Research Archive
• Axfors, Cathrine; Schmitt, Andreas; Janiaud, Perrine; Hooft, Janneke; Abd-Elsalam, Sherief & Abdo, Ehab [Show all 50 contributors for this article] (2021). Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature Communications. 12. doi: 10.1038/s41467-021-22446-z. Full text in Research Archive Show summary

  Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

• Cunningham, Evan B.; Hajarizadeh, Behzad; Amin, Janaki; Hellard, Margaret; Bruneau, Julie & Feld, Jordan J. [Show all 23 contributors for this article] (2021). Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs. Clinical Infectious Diseases. ISSN 1058-4838. 72(8), p. 1392–1400. doi: 10.1093/cid/ciaa253. Full text in Research Archive
• Fadnes, Lars T.; Aas, Christer Frode; Vold, Jørn Henrik; Leiva, Rafael Alexander Mo; Ohldieck, Christian & Chalabianloo, Fatemeh [Show all 13 contributors for this article] (2021). Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV). PLoS Medicine. ISSN 1549-1277. 18(6). doi: 10.1371/journal.pmed.1003653. Full text in Research Archive Show summary

  Background The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. Methods and findings INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. Conclusions Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV.

• Midgard, Håvard; Ulstein, Kjersti Anne; Backe, Øystein; Foshaug, Tarjei; Sørli, Hanne & Vennesland, Kristin [Show all 11 contributors for this article] (2021). Hepatitis C treatment and reinfection surveillance among people who inject drugs in a low-threshold program in Oslo, Norway. International journal of drug policy. ISSN 0955-3959. 96. doi: 10.1016/j.drugpo.2021.103165. Full text in Research Archive
• Barratt-Due, Andreas; Olsen, Inge Christoffer; Nezvalova-Henriksen, Katerina; Kåsine, Trine; Lund-Johansen, Fridtjof & Hoel, Hedda Benedicte [Show all 43 contributors for this article] (2021). Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Annals of Internal Medicine. ISSN 0003-4819. 174(9), p. 1261–1269. doi: 10.7326/M21-0653. Full text in Research Archive Show summary

  Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). Setting: 23 hospitals in Norway. Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. Limitation: The trial had no placebo group. Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.

• Gahrton, Caroline; Håkansson, Anders; Kåberg, Martin; Jerkeman, Anna; Häbel, Henrike & Dalgard, Olav [Show all 8 contributors for this article] (2021). Mortality among amphetamine users with hepatitis C virus infection: A nationwide study. PLOS ONE. 16(6), p. 1–15. doi: 10.1371/journal.pone.0253710. Full text in Research Archive Show summary

  Aims To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population. Methods In this national register study of mortality in persons notified with HCV infection 1990–2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086). Results Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45–2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73–0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals. Conclusions This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.

• Midgard, Håvard; Finbråten, Ane-Kristine; Malme, Kristian Nødtvedt; Berg-Pedersen, Riikka Mari; Tanum, Lars Håkon Reiestad & Christoffer, Olsen Inge [Show all 8 contributors for this article] (2020). Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs. Trials. 21(1), p. 524–524. doi: 10.1186/s13063-020-04434-8. Full text in Research Archive Show summary

  Background: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. Methods: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. Discussion: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care.

• Lyngbakken, Magnus; Berdal, Jan Erik; Eskesen, Arne N; Kvale, Dag; Olsen, Inge Christoffer & Rueegg, Corina Silvia [Show all 11 contributors for this article] (2020). A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics. Nature Communications. 11:5284, p. 1–6. doi: 10.1038/s41467-020-19056-6. Full text in Research Archive Show summary

  Abstract Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.

• Artenie, Andreea A.; Cunningham, Evan B.; Dore, Gregory J.; Conway, Brian; Dalgard, Olav & Powis, Jeff [Show all 22 contributors for this article] (2020). Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study. Clinical Infectious Diseases. ISSN 1058-4838. 70(11), p. 2369–2376. doi: 10.1093/cid/ciz633. Full text in Research Archive
• Hajarizadeh, Behzad; Cunningham, Evan B.; Valerio, Heather; Martinello, Marianne; Law, Matthew & Janjua, Naveed Z. [Show all 13 contributors for this article] (2020). Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis. Journal of Hepatology. ISSN 0168-8278. 72(4), p. 643–657. doi: 10.1016/j.jhep.2019.11.012. Full text in Research Archive
• Gahrton, Caroline; Westman, Gabriel; Lindahl, Karin; Öhrn, Fredrik; Dalgard, Olav & Lidman, Christer [Show all 10 contributors for this article] (2019). Prevalence of Viremic hepatitis C, hepatitis B, and HIV infection, and vaccination status among prisoners in Stockholm County. BMC Infectious Diseases. 19(1). doi: 10.1186/s12879-019-4581-3. Full text in Research Archive Show summary

  Background Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. Methods A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. Results The median age was 35 (IQR 26–44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. Conclusions The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.

• Safreed-Harmon, Kelly; Blach, Sarah; Aleman, Soo; Bollerup, Signe; Cooke, Graham & Dalgard, Olav [Show all 17 contributors for this article] (2019). The Consensus Hepatitis C Cascade of Care: standardized reporting to monitor progress toward elimination. Clinical Infectious Diseases. ISSN 1058-4838. 69(12), p. 2218–2227. doi: 10.1093/cid/ciz714. Full text in Research Archive Show summary

  Abstract Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.

• Gulati, Rachna Shridhar; Wimalanathan, Thakshani; Andersen, Solveig Norheim; Isaksen, Kjetil; Lagging, Martin & Midgard, Håvard [Show all 8 contributors for this article] (2019). The relationship between IFNL4 genotype and the rate of fibrosis in hepatitis C patients. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 54(9), p. 1172–1175. doi: 10.1080/00365521.2019.1643403. Full text in Research Archive
• Cunningham, Evan B.; Hajarizadeh, Behzad; Amin, Janaki; Litwin, Alain; Gane, Edward & Cooper, Curtis [Show all 22 contributors for this article] (2019). Adherence to once-daily and twice-daily direct-acting antiviral therapy for Hepatitis C infection among people with recent injection drug use or current opioid agonist therapy. Clinical Infectious Diseases. ISSN 1058-4838. 71(7), p. E115–E124. doi: 10.1093/cid/ciz1089. Full text in Research Archive
• Fadnes, Lars T.; Aas, Christer Frode; Vold, Jørn Henrik; Ohldieck, Christian; Leiva, Rafael Alexander Mo & Chalabianloo, Fatemeh [Show all 13 contributors for this article] (2019). Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV). BMC Infectious Diseases. 19:943, p. 1–9. doi: 10.1186/s12879-019-4598-7. Full text in Research Archive Show summary

  Background: A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. Methods: INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. Discussion: This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up.

• Fraser, Hannah; Martin, Natasha K.; Brummer-Korvenkontio, Henrikki; Carrieri, Patrizia; Dalgard, Olav & Dillon, John [Show all 23 contributors for this article] (2018). Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe. Journal of Hepatology. ISSN 0168-8278. 68(3), p. 402–411. doi: 10.1016/j.jhep.2017.10.010. Full text in Research Archive Show summary

  Background & Aims Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. Methods We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. Results At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38–63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12–24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18–79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5–17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20–80%. Conclusions The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe.

• Bjøro, Benedikte; Dalgard, Olav; Midgard, Håvard; Verbaan, Hans; Småstuen, Milada Cvancarova & Rustøen, Tone (2018). Increased hope following successful treatment for hepatitis C infection. Journal of Advanced Nursing. ISSN 0309-2402. 74(3), p. 724–733. doi: 10.1111/jan.13487. Full text in Research Archive
• Day, Emma; Hellard, Margaret; Treloar, Carla; Bruneau, Julie; Martin, Natasha K. & Øvrehus, Anne [Show all 19 contributors for this article] (2018). Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework. Liver international (Print). ISSN 1478-3223. p. 1–11. doi: 10.1111/liv.13949. Full text in Research Archive
• Grebely, Jason; Dalgard, Olav; Conway, Brian; Cunningham, Evan B.; Bruggmann, Philip & Hajarizadeh, Behzad [Show all 31 contributors for this article] (2018). Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 3(3), p. 153–161. doi: 10.1016/S2468-1253(17)30404-1. Full text in Research Archive Show summary

  Background Despite revised guidelines that no longer exclude people who inject drugs (PWID) from treatment for hepatitis C virus (HCV) infection, many clinicians are reluctant to treat recent PWID. This study aimed to evaluate the efficacy of sofosbuvir and velpatasvir therapy in people with chronic HCV infection and recent injection drug use. Methods In this open-label, single-arm phase 4 trial (SIMPLIFY), we recruited participants with recent injection drug use (past 6 months) and chronic HCV genotype 1–6 infection from seven countries (19 sites). Participants received oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. Therapy was given in 1-week electronic blister packs to record the time and date of each dose. The primary endpoint was the proportion of patients with sustained virological response 12 weeks after completion of treatment (SVR12; defined as HCV RNA <12 IU/mL), analysed in all patients who received at least one dose. This study is registered with ClinicalTrials.gov, number NCT02336139, and follow-up is ongoing to evaluate the secondary endpoint of HCV reinfection. Findings Between March 29, and Oct 31, 2016, we enrolled 103 participants; 29 (28%) of whom were female, nine (9%) had cirrhosis, 36 (35%) had HCV genotype 1, five (5%) had genotype 2, 60 (58%) had genotype 3, and two (2%) had genotype 4. 61 (59%) participants were receiving opioid substitution therapy during the study, 76 (74%) injected in the past month, and 27 (26%) injected at least daily in the past month. 100 (97%) of 103 participants completed treatment; two people were lost to follow-up and one person died from an overdose. There were no virological failures. 97 (94%, 95% CI 88–98) of 103 people achieved SVR12. Three participants with an end-of-treatment response did not have a SVR; two were lost to follow-up and one had reinfection. Drug use before and during treatment did not affect SVR12. Treatment-related adverse events were seen in 48 (47%) patients (one grade 3, no grade 4). Seven (7%) patients had at least one serious adverse event; only one such event (rhabdomyolysis, resolved) was possibly related to the therapy. One case of HCV reinfection was observed. Interpretation HCV treatment should be offered to PWID, irrespective of ongoing drug use. Recent injection drug use should not be used as a reason to withhold reimbursement of HCV therapy.

• Safreed-Harmon, Kelly; Hetherington, Kristina L.; Aleman, Soo; Alho, Hannu; Dalgard, Olav & Frisch, Tove [Show all 9 contributors for this article] (2018). Policy responses to hepatitis C in the Nordic countries: Gaps and discrepant reporting in the Hep-Nordic study. PLOS ONE. 13(1). doi: 10.1371/journal.pone.0190146. Full text in Research Archive Show summary

  Background and aims In the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), the prevalence of chronic hepatitis C virus (HCV) infection is relatively low in the general population, but is much higher among people who inject drugs (PWID). We conducted an exploratory study to investigate the extent to which these countries have policies supporting key elements of the public health response that is necessary to achieve the global goal of eliminating HCV as a public health threat. Methods Fourteen stakeholders representing government agencies, medical societies, and civil society organisations (CSOs) in the Nordic countries completed a cross-sectional online survey that included 21 policy questions related to national coordination, prevention, testing, linkage to care, and treatment. We summarised the findings in a descriptive analysis, and noted discrepant responses from stakeholders within the same country. Results Stakeholders reported that three of the five study countries have national viral hepatitis strategies, while only Iceland has a national HCV elimination goal. The availability of harm reduction services varies, with opioid substitution therapy provided for the general population throughout all countries, but not needle and syringe programmes. No country has access to anonymous HCV testing in all parts of the country. National HCV treatment guidelines are available in all countries except Finland, and all countries provide publicly funded direct-acting antiviral treatment. Disagreement regarding policies was observed across countries, and CSOs were the stakeholder group that most frequently answered survey questions incorrectly. Conclusion The Nordic region as a whole has not consistently expressed its commitment to tackling HCV, despite the existence of large HCV epidemics among PWID in these countries. Stakeholder alignment and an established elimination goal with an accompanying strategy and implementation plan should be recognised as the basis for coordinated national public health efforts to achieve HCV elimination in the Nordic region and elsewhere.

• Grebely, Jason; Conway, Brian; Cunningham, Evan B.; Fraser, Chris; Moriggia, Alberto & Gane, Edward [Show all 29 contributors for this article] (2018). Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy. International journal of drug policy. ISSN 0955-3959. 62, p. 94–103. doi: 10.1016/j.drugpo.2018.10.004. Full text in Research Archive
• Cunningham, Evan B.; Amin, Janaki; Feld, Jordan J.; Bruneau, Julie; Dalgard, Olav & Powis, Jeff [Show all 28 contributors for this article] (2018). Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: The SIMPLIFY study. International journal of drug policy. ISSN 0955-3959. 62, p. 14–23. doi: 10.1016/j.drugpo.2018.08.013. Full text in Research Archive
• Wisløff, Torbjørn; White, Richard Aubrey; Dalgard, Olav; Amundsen, Ellen Johanna; Meijerink, Hinta & Løvlie, Astrid Louise [Show all 7 contributors for this article] (2018). Economic Evaluation of Direct-Acting Antivirals for Hepatitis C in Norway. PharmacoEconomics (Auckland). ISSN 1170-7690. 36(5), p. 591–601. doi: 10.1007/s40273-017-0604-3. Full text in Research Archive Show summary

  Purpose New direct-acting antiviral (DAA) drugs have revolutionized the treatment of hepatitis C in recent years. Objective Our objective was to analyse the cost effectiveness of combinations of different DAAs compared with ribavirin and peginterferon-α-2a, taking into account rebates from tender negotiations. Methods We used a compartmental model specifically developed for Norway to simulate hepatitis C and complications with and without different DAAs. All costs were based on Norwegian fees and estimates, estimating healthcare sector costs for the year 2016. We performed Monte Carlo simulations on uncertain input parameters to facilitate probabilistic sensitivity analyses. Results For patients diagnosed with genotype 1, the combination of paritaprevir, ritonavir, ombitasvir and dasabuvir was cost effective compared with eight other available alternatives, given a cost-effectiveness threshold of €70,000 per quality-adjusted life-year. For genotype 2, the combination of sofosbuvir and ribavirin was the most effective and cost-effective alternative for all patients. Among available alternatives for patients with genotype 3, sofosbuvir in combination with peginterferon and ribavirin was the most cost-effective alternative, although the combination of daclatasvir and sofosbuvir was somewhat more effective. Conclusions For each of the hepatitis C genotypes 1, 2 and 3, there were combinations of DAAs that were cost effective in a Norwegian setting. As a result of recent tender negotiations in Norway, treating all diagnosed patients with hepatitis C with the most cost-effective DAAs will result in lower total expenditure on these medications compared with 2015.

• Wisløff, Torbjørn; White, Richard Aubrey; Dalgard, Olav; Amundsen, Ellen Johanna; Meijerink, Hinta & Kløvstad, Hilde (2018). Feasibility of reaching world health organization targets for hepatitis C and the cost‐effectiveness of alternative strategies. Journal of Viral Hepatitis. ISSN 1352-0504. 25(9), p. 1066–1077. doi: 10.1111/jvh.12904. Full text in Research Archive Show summary

  New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed 2 different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy (OST), a clean needle and syringe programme and a combination of both. The most cost‐effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduces the incidence of hepatitis C by 2030 by 63% compared with the current incidence. The 2 harm reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase in the current clean needles and syringe programme with OST was clearly the most cost‐effective option. This strategy would reduce the incidence of hepatitis C by 80% compared with the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost‐effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives.

• Meijerink, Hinta; White, Richard; Løvlie, Astrid Louise; Blasio, Birgitte Freiesleben De; Dalgard, Olav & Amundsen, Ellen Johanna [Show all 8 contributors for this article] (2017). Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973–2030. BMC Infectious Diseases. 17. doi: 10.1186/s12879-017-2631-2. Full text in Research Archive Show summary

  Background Lack of Hepatitis C virus (HCV) incidence data in (Norwegian) high-risk groups impedes the ability to make informed decisions on prevention measures. Thus we rely on modelling to estimate the incidence and burden of HCV infections. Methods We constructed a compartmental model for HCV infections in Norway among active and former people who inject drugs (PWIDs). We based yearly transition rates on literature. The model was fitted to absolute numbers of hepatitis C associated cirrhosis, hepatocellular carcinoma (HCC) and death from national data sources (2000–2013). We estimated the number (95%CI) of HCV infections, cirrhosis, HCC and death and disability adjusted life years (DALYs) due to HCV infections in Norway, 1973–2030. We assumed treatment rates in the projected period were similar to those in 2013. Results The estimated proportion of chronic HCV (including those with cirrhosis and HCC) among PWIDs was stable from 2000 (49%; 4441/9108) to 2013 (43%; 3667/8587). We estimated that the incidence of HCV among PWIDs was 381 new infections in 2015. The estimated number of people with cirrhosis, HCC, and liver transplant was predicted to increase until 2022 (1537 people). DALYs among active PWIDs estimated to peak in 2006 (3480 DALYs) and decrease to 1870 DALYs in 2030. Chronic HCV infection contributes most to the total burden of HCV infection, and peaks at 1917 DALYs (52%) in 2007. The burden of HCV related to PWID increased until 2006 with 81/100,000 DALYs inhabitants and decreased to 68/100,000 DALYs in 2015. Conclusion The burden of HCV associated with injecting drug use is considerable, with chronic HCV infection contributing most to the total burden. This model can be used to estimate the impact of different interventions on the HCV burden in Norway and to perform cost-benefit analyses of various public health measures.

• Cunningham, Evan B.; Hajarizadeh, Behzad; Dalgard, Olav; Amin, Janaki; Hellard, Margaret & Foster, Graham R. [Show all 48 contributors for this article] (2017). Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: The ACTIVATE study. BMC Infectious Diseases. 17(1). doi: 10.1186/s12879-017-2517-3. Full text in Research Archive Show summary

  Background The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. Methods ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). Results Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9–193.8). Conclusions This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy.

• Dalgard, Olav; Weiland, Ola; Noraberg, Geir; Karlsen, Lars Normann; Heggelund, Lars & Färkkilä, Martti [Show all 17 contributors for this article] (2017). Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections - A Scandinavian real-life study. PLOS ONE. 12:e0179764(7), p. 1–8. doi: 10.1371/journal.pone.0179764. Full text in Research Archive Show summary

  Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

• Lamoury, François M.J.; Soker, Angelica; Martinez, Danica; Hajarizadeh, Behzad; Cunningham, Evan B. & Cunningham, Philip [Show all 18 contributors for this article] (2017). Hepatitis C virus core antigen: A simplified treatment monitoring tool, including for post-treatment relapse. Journal of Clinical Virology. ISSN 1386-6532. 92, p. 32–38. doi: 10.1016/j.jcv.2017.05.007. Full text in Research Archive
• Blach, sarah; zeuzem, stefan; Manns, Michael; Altraif, Ibrahim; Duberg, Ann-Sofi & Muljono, David H [Show all 59 contributors for this article] (2017). Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/S2468-1253(16)30181-9. Full text in Research Archive Show summary

  Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013.Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data.Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insuffi cient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively).Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections.

• Grebely, Jason; Bruneau, Julie; lazarus, jeffrey; Dalgard, Olav; Bruggmann, Philip & Treloar, Carla [Show all 28 contributors for this article] (2017). Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs. International journal of drug policy. ISSN 0955-3959. 47, p. 51–60. doi: 10.1016/j.drugpo.2017.05.019. Full text in Research Archive Show summary

  Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection.

• Grebely, Jason; Dalgard, Olav; Cunningham, Evan B.; Hajarizadeh, Behzad; Foster, Graham R. & Bruggmann, Philip [Show all 23 contributors for this article] (2017). Efficacy of response-guided directly observed pegylated interferon and self-administered ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: The ACTIVATE study. International journal of drug policy. ISSN 0955-3959. 47, p. 177–186. doi: 10.1016/j.drugpo.2017.05.020. Full text in Research Archive Show summary

  Background There are few data on treatment for hepatitis C virus (HCV) infection among people with ongoing injecting drug use. This study evaluated the efficacy of response-guided therapy for chronic HCV genotypes 2/3 infection among people with ongoing injecting drug use or receiving opioid substitution therapy (OST). A secondary aim was to identify predictors of HCV treatment response. Methods ACTIVATE was a multicentre clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Participants were recruited from drug treatment clinics, private practices, hospital clinics and community clinics in Australia, Canada, and five countries in Europe. The primary study outcome was sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). Results Among 93 people with ongoing injecting drug use or receiving OST treated for HCV genotype 2/3, 59% had recently (past month) injected drugs, 77% were receiving OST and 56% injected drugs during therapy. Overall SVR was 66% (61/93). SVR was 84% in those with undetectable HCV RNA at week 4 (12 weeks) compared to 38% in those without (24 weeks). In adjusted analysis, cirrhosis vs. no/mild fibrosis [adjusted OR (aOR) 0.33, 95% CI 0.13, 0.86] predicted reduced SVR, while response at week 4 was associated with increased SVR [aOR 8.11, 95% CI 2.73, 24.10]. Recent injecting drug use at baseline or during therapy was not associated with SVR. Conclusion This study demonstrates that people with recent injecting drug use or OST with chronic HCV can achieve responses to interferon-based therapy similar to other populations, despite injecting drugs prior to or during therapy. Cirrhosis was predictive of reduced response to HCV therapy, while response at week 4 (despite shortened therapy) was predictive of improved response.

• Midgard, Håvard; Hajarizadeh, Behzad; Cunningham, Evan B.; Conway, Brian; Backmund, Markus & Bruggmann, Philip [Show all 20 contributors for this article] (2017). Changes in risk behaviours during and following treatment for hepatitis C virus infection among people who inject drugs: The ACTIVATE study. International journal of drug policy. ISSN 0955-3959. 47, p. 230–238. doi: 10.1016/j.drugpo.2017.05.040. Full text in Research Archive
• Midgard, Håvard; Bjøro, Benedikte; Mæland, Arild; Zbigniew, Konopski; Kileng, Hege & Damås, Jan Kristian [Show all 15 contributors for this article] (2016). Hepatitis C reinfection after sustained virological response. Journal of Hepatology. ISSN 0168-8278. 64(5), p. 1020–1026. doi: 10.1016/j.jhep.2016.01.001. Full text in Research Archive
• Dore, Gregory J.; Altice, Frederick; Litwin, Alain H; Dalgard, Olav; Gane, Edward J. & Shibolet, Oren [Show all 22 contributors for this article] (2016). Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial. Annals of Internal Medicine. ISSN 0003-4819. 165(9), p. 625–634. doi: 10.7326/M16-0816. Full text in Research Archive
• Waldenström, Jesper; Westin, Johan; Nyström, Kristina; Christensen, Peer; Dalgard, Olav & Färkkilä, Martti [Show all 14 contributors for this article] (2016). Randomized trial evaluating the impact of ribavirin mono-therapy and double dosing on viral kinetics, ribavirin pharmacokinetics and anemia in hepatitis C virus genotype 1 infection. PLOS ONE. 11(5). doi: 10.1371/journal.pone.0155142. Full text in Research Archive
• Midgard, Håvard; Weir, Amanda; Palmateer, Nora; 3rd, Vincent Lo Ve; Pineda, Juan A. & Macias, Juan [Show all 7 contributors for this article] (2016). HCV epidemiology in high-risk groups and the risk of reinfection. Journal of Hepatology. ISSN 0168-8278. 1 Suppl , p. 33–45. doi: 10.1016/j.jhep.2016.07.012. Full text in Research Archive
• Dore, Gregory J.; Conway, Brian; Luo, Yan; Janczewska, Ewa; Knysz, Brygida & Liu, Yan [Show all 26 contributors for this article] (2016). Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials. Journal of Hepatology. ISSN 0168-8278. 64(1), p. 19–28. doi: 10.1016/j.jhep.2015.08.015. Full text in Research Archive
• Midgard, Håvard; Bramness, Jørgen Gustav; Skurtveit, Svetlana; Haukeland, John Willy & Dalgard, Olav (2016). Hepatitis C Treatment Uptake among Patients Who Have Received Opioid Substitution Treatment: A Population-Based Study. PLOS ONE. 11(11). doi: 10.1371/journal.pone.0166451. Full text in Research Archive Show summary

  Background and Aims There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway. Methods This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied. Results Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7-2.2) in 2005 and 2.6% (95% CI 1.9-3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07-1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17-2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49-0.87). Conclusions Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced.

• Saraswat, Vivek Anand; Norris, S; Knegt, RJ De; Avila, JF Sanchez; Sonderup, M & Zuckerman, E [Show all 94 contributors for this article] (2015). Historical epidemiology of hepatitis C virus (HCV) in select countries - Volume 2. Journal of Viral Hepatitis. ISSN 1352-0504. 22(1), p. 6–25. doi: 10.1111/jvh.12350. Full text in Research Archive
• Gane, Edward J.; Kershenobich, D; Seguin-Devaux, C; Kristian, P; Aho, I & Dalgard, Olav [Show all 94 contributors for this article] (2015). Strategies to manage hepatitis C virus (HCV) infection disease burden - Volume 2. Journal of Viral Hepatitis. ISSN 1352-0504. 22(1), p. 46–73. doi: 10.1111/jvh.12352. Full text in Research Archive
• Hatzakis, Angelos; Chulanov, V; Gadano, AC; Bergin, C; Ben-Ari, Z & Mossong, J [Show all 94 contributors for this article] (2015). The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - Volume 2. Journal of Viral Hepatitis. ISSN 1352-0504. 22(1), p. 26–45. doi: 10.1111/jvh.12351. Full text in Research Archive
• Dalgard, Olav; Martinot-Peignoux, Michelle; Verbaan, Hans; Bjøro, Kristian; Ring-Larsen, Helmer & Marcellin, Patrick (2015). The usefulness of defining rapid virological response by a very sensitive assay (TMA) during treatment of HCV genotype 2/3 infection. PLOS ONE. 10(8). doi: 10.1371/journal.pone.0120866. Full text in Research Archive
• Isaksen, Kjetil; Aabakken, Lars; Grimstad, Tore; Karlsen, Lars Normann; Sandvei, Per & Dalgard, Olav (2015). Hepatitt C-behandling ved tre norske sykehus 2000–11. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 135(22), p. 2052–2058. doi: 10.4045/tidsskr.14.1478. Full text in Research Archive
• Kielland, Knut Boe; Delaveris, Gerd Jorunn Møller; Rogde, Sidsel; Eide, Tor Jacob; Amundsen, Ellen Johanna & Dalgard, Olav (2014). Liver fibrosis progression at autopsy in injecting drug users infected by hepatitis C: A longitudinal long-term cohort study. Journal of Hepatology. ISSN 0168-8278. 60(2), p. 260–266. doi: 10.1016/j.jhep.2013.09.022. Full text in Research Archive Show summary

  There is a paucity of unbiased data on the natural history of hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of this study was to assess the risk of developing advanced fibrosis associated with chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who underwent an autopsy. A longitudinal cohort design was applied, in which the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV infection was assessed in liver tissue from autopsies performed up to 35years after HCV exposure. The cohort originated from 864 IDUs consecutively admitted for drug abuse treatment 1970–1984. Stored sera, mostly drawn at the time of admission for drug treatment, were available in 635 subjects. 220 out of 523 anti-HCV positive subjects had died before 2009. Liver tissue from autopsies was available from 102/220 subjects, of which 61 were HCV RNA positive. Liver sections were classified according to METAVIR scores for fibrosis. Two pathologists, both blinded for serologic results, scored sections of liver tissue. Among HCV RNA positive subjects 16.4% (10/61) had septal fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV positive/HCV RNA negative subjects (p=0.026). Of 18 HCV RNA positive subjects autopsied <15years after HCV exposure none had F3 or F4. Among subjects autopsied >25years after exposure 35% (6/17) had F3–F4. Among IDUs chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25years or more after exposure.

• Kielland, Knut Boe; Amundsen, Ellen Johanna & Dalgard, Olav (2014). HCV treatment uptake in people who have injected drugs — observations in a large cohort that received addiction treatment 1970–1984. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 49(12), p. 1465–1472. doi: 10.3109/00365521.2014.968860. Full text in Research Archive Show summary

  The aim of this study was to document antiviral treatment uptake among former or current people who inject drugs (PWID) with chronic hepatitis C and to explore a possible association between treatment and mortality. This is a longitudinal cohort study of PWID admitted for drug abuse treatment 1970-1984. The 245 hepatitis C virus (HCV) RNA-positive patients alive by the end of 1996 were followed 1997-2012 through linkage to several health registers. Treatment uptake was mainly documented by information on prescription of antiviral medication registered in the Norwegian Prescription Database from 2004. Cox regression, with a time-dependent covariate measuring end-of-treatment, was employed to evaluate mortality after treatment. At the end of the follow-up, median time since HCV exposure was 36 years, and 19.2% (47/245) had been prescribed antiviral treatment for chronic HCV infection. No gender difference was observed. Among those alive at the end of the study period, 27.8% (44/158) had been treated. Relative hazard of death was 0.21 (95% confidence interval [CI] 0.07-0.68), comparing periods for patients after versus before or without treatment. Mortality rate after treatment was 0.8 per 100 person years (95% CI 0.3-2.4) compared to 2.8 (95% CI 2.2-3.5) in untreated patients and before treatment. The most important causes of death among the untreated were drug-related. Among PWID infected with HCV, approximately one-fourth of those still alive at a median of 36 years after exposure had received HCV treatment. Treatment was associated with increased survival, probably mainly due to selection bias.

• Kielland, Knut Boe; Skaug, Kjell; Amundsen, Ellen Johanna & Dalgard, Olav (2013). All-cause and liver-related mortality in hepatitis C infected drug users followed for 33 years: a controlled study. Journal of Hepatology. ISSN 0168-8278. 58(1), p. 31–37. doi: 10.1016/j.jhep.2012.08.024. Full text in Research Archive Show summary

  The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection. A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment 1970-1984 and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV Ribonucleic Acid (RNA). All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). Observation was accomplished through register linkage to national registers. Mean observation time was 33 years. All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, males 2.11 (95% CI 1.84-2.46), females 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after age 50 were caused by liver disease. The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until they reach the age of 50 years, HCV infection emerges as a main cause of death.

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• Midgard, Håvard; Malme, Kristian Nødtvedt; Finbråten, Ane-Kristine & Dalgard, Olav (2025). Treatment Completion and Sustained Virologic Response in the Context of Hepatitis C Virus Elimination: Time to Let Go of the Reins? Clinical Infectious Diseases. ISSN 1058-4838. 80(3), p. 684–685. doi: 10.1093/cid/ciae298. Full text in Research Archive
• Johannessen, Asgeir; Reikvam, Dag Henrik & Dalgard, Olav (2024). Letter: Should HBV Therapy Be Stopped Based on HBsAg Level Alone? Authors' Reply. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 61(2), p. 404–405. doi: 10.1111/apt.18439. Full text in Research Archive
• Axfors, Cathrine; Schmitt, Andreas M.; Janiaud, Perrine; Hooft, Janneke van’t; Abd-Elsalam, Sherief & Abdo, Ehab F. [Show all 94 contributors for this article] (2024). Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials(Nature Communications, (2021), 12, (1), 10.1038/s41467-021-22446-z). Nature Communications. 15(1). doi: 10.1038/s41467-024-45360-6. Full text in Research Archive
• Hites, Maya; Lapique, Eva Larranaga; Massonnaud, Clément R.; Belhadi, Drifa; Jamard, Simon & Goehringer, François [Show all 86 contributors for this article] (2024). Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial. Journal of Infection. ISSN 0163-4453. 88(3). doi: 10.1016/j.jinf.2024.106120. Full text in Research Archive
• Axfors, Cathrine; Schmitt, Andreas M.; Janiaud, Perrine; Hooft, Janneke van’t; Abd-Elsalam, Sherief & Abdo, Ehab F. [Show all 94 contributors for this article] (2021). Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials (Nature Communications, (2021), 12, 1, (2349), 10.1038/s41467-021-22446-z). Nature Communications. 12(1). doi: 10.1038/s41467-021-23559-1. Full text in Research Archive
• Hauge, Joakim; Kielland, Knut Boe; Jarnaess, E.; Midgard, Håvard & Dalgard, Olav (2021). The HEPRIS Study -Prevalence of Hepatitis C in Norwegian Prisons. Full text in Research Archive
• Lyngbakken, Magnus; Berdal, Jan Erik; Eskesen, Arne N; Kvale, Dag; Christoffer, Olsen Inge & Rangberg, Anbjørg [Show all 10 contributors for this article] (2020). Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial. Trials. 21. doi: 10.1186/s13063-020-04420-0. Full text in Research Archive
• Midgard, Håvard; Kielland, Knut Boe & Dalgard, Olav (2018). Eliminasjon av hepatitt C er mulig. 138(7), p. 630–633. doi: 10.4045/tidsskr.18.0099. Full text in Research Archive
• Grebely, Jason; Swan, Tracy; hickman, matthew; Bruneau, Julie; Bruggmann, Philip & Dalgard, Olav [Show all 9 contributors for this article] (2017). Contradictory advice for people who inject drugs in the 2016 EASL Recommendations on Treatment of Hepatitis C. Journal of Hepatology. ISSN 0168-8278. 66(5), p. 1101–1103. doi: 10.1016/j.jhep.2016.12.028. Full text in Research Archive
• Razavi-Shearer, D; Dalgard, Olav; Midgard, Håvard; Razavi, H; Wüsthoff, Linda Elise & Kielland, Knut Boe (2016). Aggressive treatment of hepatitis C in People who inject drugs in Norway: an integral step to eradicate the infection in this population. Full text in Research Archive
• Hjerrild, Simon; Dalgard, Olav; Christensen, Peer Brehm & Leutscher, Peter (2015). Debilitating fatigue as a treatment indication in chronic hepatitis C. Journal of Hepatology. ISSN 0168-8278. 63(6), p. 1533–1533. doi: 10.1016/j.jhep.2015.08.003. Full text in Research Archive
• Whittaker, Robert; Kløvstad, Hilde; Blindheim, Martin Ingvald; Skullerud, Kristin Helene; Dalgard, Olav & Midgard, Håvard [Show all 9 contributors for this article] (2023). Statusrapport om eliminasjon av hepatitt B og C som folkehelseproblem i Norge. Folkehelseinstituttet. Full text in Research Archive Show summary

  Helse- og omsorgsdepartementet lanserte en nasjonal strategi mot virale hepatitter i 2016, som ble videreutviklet i 2018. Hepatitt B virus- (HBV) og hepatitt C virus- (HCV) infeksjon er globalt ledende årsaker til leverkreft og leversvikt. I Norge anses prevalensen av kronisk HBV- og HCV-infeksjon for å være lav i den generelle befolkningen, men forekomsten har vært høy i risikoutsatte grupper, særlig blant personer som har injisert rusmidler og innvandrere fra land med høy prevalens av hepatitt B eller C. I tråd med FNs globale bærekraftsmål og WHO sin globale helsestrategi har Norge som mål å eliminere hepatitt B og C som folkehelseproblem. Med ‘eliminasjon’ menes reduksjon av smitte og sykdom til et så lavt nivå at det ikke lenger utgjør et problem for folkehelsen. Eliminasjon defineres for flere områder, inkludert insidens av nye tilfeller, insidens av alvorlig sykdom og dødsfall og dekningsmål i helsetjenesten. Dekningsmål omfatter oppfølgning i helsetjenesten, behandlingsopptak, vaksinasjonsdekning, trygge blodprodukter og injeksjoner, og skadereduserende tiltak. Formålet med denne rapporten er å: • Presentere oppdatert kunnskap om forekomst av hepatitt B og C i Norge. • Vurdere status for de igangsatte tiltakene i hepatittstrategiene opp mot nasjonale og internasjonale mål. • Gi råd for videreføring av arbeidet mot eliminasjon av hepatitt B og C som folkehelseproblem i Norge.

• Litleskare, Irene; Bragstad, Karoline; Kran, Anne-Marte Bakken; Kanestrøm, Anita; Stene-Johansen, Kathrine & Kro, Grete Birkeland [Show all 10 contributors for this article] (2018). Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2017. Norwegian Institute of Public Health, Department for Infectious disease registries. ISSN 9788280829733. Full text in Research Archive Show summary

  Bruk av antivirale midler Salget av antivirale medikamenter fortsetter å øke målt i definerte døgndoser (DDD). Kostnadene for antiinfeksiøse agens for systemisk bruk (ATC gruppe J) har også økt de seneste år, men i mindre grad etter 2016. Introduksjon av nye antiviralia for behandling av HCV infeksjon har influert sterkt på de økte kostnadene, men prisreduksjon på noen av disse medikamentene har gitt mindre økning i kostnader sammenlignet med økning i salg. For hiv-medikamenter har salget målt i antall DDD vært relativt stabilt de siste årene, men det har vært en dreining fra medikamenter med ett virkestoff til kombinasjonspreparater. Influensavirus Som i forrige sesong, ble det i 2017/18-sesongen ikke påvist influensavirus med resistens mot oseltamivir eller zanamivir. De få H1N1-virus som sirkulerte denne sesongen, videreførte dermed ikke den resistensen som ble påvist på slutten av 2015/16-sesongen. Alle sirkulerende influensavirusgrupper er for tiden resistente overfor adamantaner, og FHI har derfor sluttet å teste rutinemessig for adamantanresistens. Kun oseltamivir er nå tilgjengelig på det norske markedet. Hiv-1 Surveillance drug-resistance mutations (SDRMs) ble påvist i 5.6% av prøvene fra pasienter med ny diagnostisert hiv-1 infeksjon i Norge i 2017. Prevalensen av overført resistens har vært stabil de siste årene med bare små variasjoner. Innføring av profylaktisk behandling (PrEP og PEP) kan endre denne situasjonen. En studie pågår i regi av RAVN der resistensdata kobles mot ulike epidemiologiske variabler fra MSIS. Foreløpige resultater fra denne studien viser at bare 30% av de tilfellene der primær resistensundersøkelse ble utført i 2016, var smittet i Norge. I denne gruppen ble det funnet SDRM i 7.5% av prøvene. Hepatitt B virus I 2017 ble 23 pasientprøver sendt til referanselaboratoriet for hepatitt B virus (HBV) resistenstesting. Det ble påvist antiviral resistens i 2 av disse prøvene. Blant pasienter der genotyping primært var rekvirert (N=223), ble ingen resistensmutasjoner påvist. Resistens mot antivirale midler brukt i behandling av HBV ser ut til å være et lite problem i Norge. Antall prøver som undersøkes er imidlertid lite, og resultatene må derfor tolkes med forsiktighet. Humane herpesvirus I 2017 mottok referanselaboratoriet prøver fra 27 pasienter for cytomegalovirus (CMV) resistenstesting, og hos 7 (26%) kunne det påvises mutasjoner i CMV-UL97 genet som gir resistens mot ganciclovir. Hos en pasient ble det funnet ytterlige mutasjoner i CMV-DNApolymerasegenet (UL54) som medfører resistens mot cidofovir og foscarnet. De fleste tilfeller av terapisvikt skyldes ikke utvikling av resistens mot CMV-midler. Aciclovir og dets prodrug valaciclovir er de mest benyttede medikamenter for behandling og profylakse mot herpes simplex virus (HSV) -1 og -2 infeksjoner. Til tross for et stort forbruk er forekomsten av behandlingssvikt, som skyldes resistens svært lav. I 2017 ble det sendt ti prøver fra pasienter med slik behandlingssvikt til Folkhälsomyndigheten i Sverige. I to av prøvene ble det funnet mutasjoner som medfører resistens mot aciclovir og valaciclovir. Hepatitt C virus Med enkelte unntak vil hepatitt C infeksjon kureres med en 12-ukers behandling med kombinasjon av 2 direktevirkende antivirale medikamenter. Behandlingen har få bivirkninger, og alle infiserte bør tilbys behandling. Behandlingssvikt hos behandlingsnaive vil kun skje hos ca. 3% av alle som behandles. Prediktorer for behandlingssvikt er bl.a. genotype 3 infeksjon, tilstedeværelse av resistensassosierte varianter (RAV) og avansert leverfibrose. Resistenstesting før behandling med enkelte unntak er ikke nødvendig.

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