Asgeir Johannessen

• Chabala, Freeman W.; Sinkala, Edford; Brennan, Alana T.; Goss, Amy Miskimon; Bojang, Lamin & Samateh, Yusupha [Vis alle 27 forfattere av denne artikkelen] (2026). Hepatic Steatosis in People With Chronic Hepatitis B in Africa: Prevalence, Correlates, and Clinical Significance. Journal of Viral Hepatitis. ISSN 1352-0504. 33(11). doi: 10.1111/jvh.70241. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT To address data gaps around metabolic liver disease in Africa, within the Hepatitis B in Africa Collaborative Network (HEPSANET), we evaluated participants with chronic hepatitis B virus infection (CHB) for steatotic liver disease (SLD) using transient elastography with controlled attenuation parameter (CAP). Using multivariable logistic regression, we identified sociodemographic, anthropometric, and clinical associations with SLD (CAP ≥ 248 dB/m), and evaluated whether SLD severity was independently associated with fibrosis. Short‐term impacts of SLD on mortality were also assessed with Cox proportional hazards analysis. We also evaluated the diagnostic performance of B‐mode ultrasound for SLD, with CAP as reference. Across 6 countries and 1601 participants (age range, 12–80 years; 39.5% female; 4% with diabetes; 11% unhealthy alcohol use; median body mass index, 24.4), 421 (26.3%) had SLD; 219 (13.7%) had severe steatosis (CAP ≥ 280 dB/m). Older age, male sex, overweight and obesity, and HIV‐negative status were associated with SLD. After adjusting for age, sex, HIV status, HBV treatment, and country, severe steatosis, but not mild and moderate forms (i.e., 248–279 dB/m), was associated with a 8.4% (95%, 1.9%–14.9%) increased probability of fibrosis. Over limited follow‐up (median 2.69 years) and small number of deaths, SLD was not associated with all‐cause or liver‐related mortality. B‐mode ultrasound had low sensitivity for SLD, overall or when severe, but specificity was 95%. In conclusion, SLD was common in people with CHB in Africa and its severe form was associated with liver fibrosis. These data support screening for metabolic comorbidities as part of HBV care and treatment in Africa.

• Asmamaw, Asegedech; Romero, Judit; Berhe, Nega; Legesse, Mengistu; Desalegn, Zelalem & Rando‐Segura, Ariadna [Vis alle 13 forfattere av denne artikkelen] (2026). Time to Positivity of a Rapid HBsAg Assay as a Surrogate Marker of Quantitative HBsAg: Multicentre Proof-of-Concept Study. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. doi: 10.1111/apt.70892. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Background and Aims Point‐of‐care (POC) diagnostics for hepatitis B virus (HBV) are limited to qualitative results. This study evaluated whether the time to positivity of a rapid HBsAg assay could serve as a surrogate marker of quantitative HBsAg (qHBsAg) and virological activity. Methods This multicentre, prospective proof‐of‐concept study included cohorts from Spain and Ethiopia. Adults with chronic or resolved HBV infection and healthy controls were enrolled. Paired venous and capillary blood samples were collected; capillary blood was tested with Determine HBsAg2 rapid test recording time to positivity, while qHBsAg and HBV DNA were measured using immunoassay and PCR, respectively. Results A total of 513 HBsAg‐positive individuals were included (263 Spain; 250 Ethiopia). All healthy controls and individuals with resolved infection tested negative. Time to positivity showed an inverse correlation with qHBsAg in both cohorts (Spain: r  = −0.749; Ethiopia: r  = −0.374; p  < 0.001 for both). No association was observed between time to positivity and HBV DNA levels. The performance to identify patients with HBsAg levels < 1000 IU/mL was higher in Spain (AUROC 0.86) than in Ethiopia (AUROC 0.65). Better performance was observed for detecting HBsAg levels < 100 IU/mL in both countries (AUROC 0.96 and 0.77, respectively). Conclusions Time to positivity in a rapid HBsAg assay correlated inversely with qHBsAg and may provide a simple, semi‐quantitative estimate of antigen burden. Although unrelated to HBV DNA, it could expand the utility of point‐of‐care HBsAg testing beyond qualitative diagnosis, particularly where quantitative HBsAg assays are unavailable.

• Asmamaw, Asegedech; Berhe, Nega; Legesse, Mengistu & Johannessen, Asgeir (2026). Dried blood spots perform well in the quantification of HBV DNA and detection of HBeAg. Virology Journal. doi: 10.1186/s12985-026-03290-3. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Hepatitis B virus (HBV) DNA quantification and hepatitis B e-antigen (HBeAg) detection are recommended in the management of chronic HBV infection. The use of dried blood spots (DBS) collected with fingerstick could improve access to these tests in resource-limited settings, but needs validation in a field setting. Methods DBS samples were collected using fingerstick capillary blood from 143 HBV-infected individuals at Sebeta Health Centre, Ethiopia, covering the total range of quantification from < 2 to > 8 log 10 IU/ml. Plasma samples were collected in parallel using standard venipuncture whole blood. The Xpert ® HBV viral load assay was used to quantify HBV DNA. HBeAg detection was performed using the Alinity i HBeAg assay. DBS and plasma viral loads were compared using linear regression analysis. Stability studies were performed in 10 DBS samples stored at ambient temperature for up to 24 weeks. Results HBV DNA was detected in all 89 DBS samples with plasma HBV DNA above the WHO-recommended decision threshold of 3.3 log 10 (= 2000) IU/ml. A strong correlation (R 2  = 0.90) was observed between plasma and DBS, with a mean difference of 0.23 log 10 IU/ml. DBS had 85.7% sensitivity and 92.9% specificity for the detection of HBeAg. No clinically relevant change of HBV DNA was observed in DBS stored at room temperature up to 12 weeks; however, a reduction of more than 0.5 log 10 IU/ml was observed in 4 of 10 DBS samples at week 24. Conclusions DBS is a reliable sample matrix for HBV DNA quantification and HBeAg detection in resource-limited settings.

• MacLeod, Julia; Gudissa, Fikadu G.; Jeylan, Asiya; Berhe, Nega; Mekonnen, Hailemichael Desalegn & Rossvoll, Lasse Olsen [Vis alle 10 forfattere av denne artikkelen] (2026). A Distinct Immune Signature Characterizes Cirrhosis in Ethiopian Individuals With Chronic <scp>HBV</scp> Infection. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. doi: 10.1111/apt.70816. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Background and Aims The immune cell phenotype of African patients living with chronic hepatitis B virus (HBV) infection is rarely described, despite high infection rates. This study investigated the differences in immune cell phenotypes in four distinct clinical phases of disease in an Ethiopian cohort. Methods Two hundred eighty‐seven patients with untreated HBV infection, and no human immunodeficiency virus and hepatitis C virus infection, were included at Adama Hospital, Ethiopia. Patients were categorized based on clinical parameters into the following groups: low‐replicative infection, “greyzone”, active hepatitis, and cirrhosis. Whole blood samples were cryopreserved using Cytodelics Whole Blood Cell Stabilizer and analysed using two high‐dimensional flow cytometry panels to define immune cell phenotypes. Results Patients with cirrhosis displayed a distinct immunophenotype compared to other phases of chronic HBV infection with an increase in monocytes and a reduction in all lymphocytes alongside a shift from a mature to a naïve phenotype in NK cells, CD4 + T cells, and B cells. The emergence of activated CD38 + HLA‐DR + cells across lymphocyte lineages defined patients with cirrhosis and the frequency of these double positive cells correlated positively with the AST to Platelet Ratio Index used as a measure of cirrhosis severity. Conclusions HBV‐associated cirrhosis in Ethiopia displayed a unique immunophenotype, in which the frequency of CD38 + HLA‐DR + NK cells and T cells correlated strongly with the severity of cirrhosis.

• Bugssa, Gessessew; Berhe, Nega; Medhin, Girmay; Nayagam, Shevanti; Teklehaymanot, Tilahun & Johannessen, Asgeir (2026). Biomarkers of chronic liver disease and their determinants in northern Ethiopia: Evaluating the synergistic impact of HBV and Schistosoma mansoni and the contribution of metabolic and lifestyle factors to liver injury. PLOS ONE. 21(6), s. 0352266–0352266. doi: 10.1371/journal.pone.0352266. Fulltekst i vitenarkiv Vis sammendrag

  Background Liver diseases are a major global health concern, affecting over 1.5 billion people and ranking among the leading causes of death. Sub-Saharan Africa carries a high burden, yet the underlying etiology of chronic liver disease is poorly described. The aim of this study was to assess biomarkers of chronic liver disease and their determinants in Northern Ethiopia. Methods A community-based cross-sectional study was conducted between December 2019 and June 2020 among randomly selected participants aged 5 years or older in Alamata district of Tigray region. Socio-demographic, behavioral, and clinical factors were collected via structured questionnaires; blood was tested for liver function biomarkers and Hepatitis B Virus (HBV) and stool samples for S.mansoni infection. Liver function biomarkers’ abnormalities were defined based on age and sex-specific thresholds. Multivariable hierarchical logistic regression analysis was performed to identify predictors of abnormal alanine aminotransferase (ALT) and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were reported. Results A total of 767 participants were included, with a median age of 27 years (5–80 years); 53.1% were female and 67.5% resided in rural areas. The prevalence of HBV and S.mansoni infection was 5.9%, and 26.6%, respectively. Overall, 23.5% of participants had abnormal liver function biomarker with 7.3%, 14.2%, 9,4%, and 8.0% had elevated aspartate aminotransferase(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin levels, respectively. Besides, the De Ritis, aspartate to alanine (AAR) ratio revealed a median of 0.96(IQR:0.62–1.74), with 51% (79/155) of the participants presented with an AAR < 1.0, and 21.3% of participants exhibited an AAR > 2.0. Moreover, the R value depicted the patterns of liver injury with 90(52.0%) participants exhibited R-value below 2(cholestatic injury), whereas 44(22.43%), and 39(22.54%) of the participants were found to have R-values between 2 and 5(mixed injury), and R > 5(hepatocellular injury), respectively. The hierarchical modeling depicted that the infectious domain accounted for the largest portion of model variance (change in Nagelkerke R-squared (ΔR 2 ) =0.157, p < .001). Accordingly, the model demonstrated that several determinants of hepatocellular injury led by significant synergistic interaction between HBV and S. mansoni co-infection conferred a 19.7-fold increase in the odds of elevated ALT (aOR:19.7; 95%CI:5.50, 70.6; p < .001), significantly higher than mono-infections of HBV (aOR:13.7; 95%CI: 5.82, 32.04; p < .001) or S. mansoni (aOR:3.4;95% CI:2.5; 5.51, p < .001). Beyond the infectious synergy, khat chewing (aOR:4.1, 95%CI:2.21, 7.58), and diabetes mellitus (aOR:4.01, 95%CI:1.55–10.36); p = .004) were confirmed as significant independent predictors, each associated with a four-fold increase in likelihood of having elevated ALT. Conclusion Liver function biomarkers’ abnormalities were common in northern Ethiopia driven by infectious, metabolic and lifestyle factors. The significant synergy between HBV and S.mansoni creates a compounded risk that far exceeds the impact of mono-infections, diabetes, or khat chewing. The findings emphasize the need for integrated public health strategies that address both infectious and non-infectious determinants simultaneously to effectively reduce the burden of chronic liver disease in the region.

• Holmberg, Marte; Niehrs, Annika; Dalgard, Olav; Berhe, Nega; Desalegn, Hailemichael & Aleman, Soo [Vis alle 20 forfattere av denne artikkelen] (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. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Simbo, Teklu Shiferaw; Schlund, Franziska; Gal, Frédéric Le; Gerber, Athenais; Zheng, Sezen & Abegaz, Woldaregay Erku [Vis alle 19 forfattere av denne artikkelen] (2026). A new hepatitis delta virus hotspot in Ethiopia: a multicenter study. International Journal of Infectious Diseases. ISSN 1201-9712. s. 108717–108717. doi: 10.1016/j.ijid.2026.108717. Fulltekst i vitenarkiv
• Dongelmans, Edo; Hirode, Grishma; Bӧmmel, Florian van; Jeng, Wen-Juei; Chien, Rong-Nan & Chen, Chien-Hung [Vis alle 34 forfattere av denne artikkelen] (2026). Long-term outcomes after nucleos(t)ide analogue cessation in chronic hepatitis B – follow-up from the RETRACT-B cohort. Journal of Hepatology. ISSN 0168-8278. doi: 10.1016/j.jhep.2026.03.030. Fulltekst i vitenarkiv
• Yucuma, Daniela; Rakover, Arthur; Warsop, Zakary Ismail; Im, Yu Ri; Chen, Si Emma & Jagdish, Rukmini [Vis alle 15 forfattere av denne artikkelen] (2026). Natural history of chronic hepatitis B in untreated adults without cirrhosis according to baseline hepatitis B virus DNA and alanine aminotransferase concentrations: a systematic review and meta-analysis. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/s2468-1253(25)00302-4. Fulltekst i vitenarkiv Vis sammendrag

  ackground: Chronic hepatitis B (CHB) affects an estimated 254 million people globally. Historically, WHO and professional society guidelines have recommended treatment for individuals at high risk of disease progression, including those with hepatitis B virus (HBV) DNA concentrations >20 000 IU/mL. Whether individuals at lower risk, including those with HBV DNA <20 000 IU/mL and normal alanine aminotransferase concentrations, benefit from treatment remains uncertain. To inform 2024 WHO guidelines and the potential expansion of treatment threshold recommendations, we conducted two linked systematic reviews and meta-analyses; this analysis examines the incidence of clinical outcomes in untreated adults with non-cirrhotic CHB stratified by baseline HBV DNA and ALT concentrations. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library for longitudinal prospective and retrospective cohort studies, randomised controlled trials, and non-randomised studies of interventions, published in any language, from Jan 1, 2000, to Feb 6, 2023. We also reviewed the reference lists of included studies and systematic reviews and consulted networks of experts to identify other data sources. Included studies followed up adults (≥18 years) with non-cirrhotic CHB who had no history of antiviral therapy at enrolment, had baseline HBV DNA quantification and ALT measurement, had a follow-up period of at least 48 weeks, and assessed one or more of six key clinical outcomes (hepatocellular carcinoma, cirrhosis, liver-related mortality, all-cause mortality, liver decompensation, and indication for liver transplantation) or six additional outcomes (advanced liver fibrosis, progression of liver fibrosis, becoming eligible for antiviral treatment, hepatitis flare, and HBsAg and HBeAg seroclearance). Outcomes were required to be stratified by HBV DNA concentrations (<200 IU/mL, <2000 IU/mL, 2000-19 999 IU/mL, 20 000-199 999 IU/mL, and ≥200 000 IU/mL) or ALT concentrations (less than the upper limit of normal [ULN], 1·0-1·9 × ULN, and ≥2·0 × ULN). We excluded studies that focused solely on individuals who were pregnant; were co-infected with HIV, hepatitis C virus, or hepatitis D virus; or had another underlying condition other than CHB. We extracted aggregate data and used random-effects meta-analysis to pool incidence rates per 100 person-years. This study was registered with PROSPERO (CRD42023431652). Findings: Of 13 231 studies screened, 71 met the inclusion criteria. A concentration-response relationship was observed between single baseline HBV DNA measurements and hepatocellular carcinoma incidence rates per 100 person-years: 0·131 (95% CI 0·097 to 0·177, I2=0%) for HBV DNA concentrations <200 IU/mL, 0·176 (0·117-0·266, I2=88%) for <2000 IU/mL, 0·311 (0·245-0·393, I2=13%) for 2000-19 999 IU/mL, 0·862 (0·725-1·026, I2=0%) for 20 000-199 999 IU/mL, and 0·941 (0·668-1·324, I2=58%) for ≥200 000 IU/mL (p<0·0001 for between-group difference). Similar concentration-response patterns were observed for development of cirrhosis (0·298 [95% CI 0·214-0·415], two studies, for <200 IU/mL; 0·300 [0·146-0·616], I2=88%, for <2000 IU/mL; 0·712 [0·624-0·814], I2=46%, for 2000-19 999 IU/mL; 1·436 [0·991-2·082], I2=76%, for 20 000-199 999 IU/mL; and 2·193 [1·690-2·846], I2=82%, for ≥200 000 IU/mL) and liver-related mortality (0·086 [95% CI 0·054-0·136], one study; 0·083 [0·015-0·451], I2=0%; 0·303 [0·228-0·402], I2=0%; 0·766 [0·591-0·993], one study; and 1·118 [0·951-1·314], two studies), but no concentration-response relationship was observed between a single baseline HBV DNA assessment and all-cause mortality or liver decompensation. Compared with ALT below the ULN, incidence rates of hepatocellular carcinoma, cirrhosis, and liver-related mortality were higher in individuals with baseline ALT concentrations 1·0-1·9 × ULN or ≥2·0 × ULN. A similar pattern was not found for all-cause mortality, and other outcomes were not meta-analysed due to small numbers. Within the HBV DNA strata of <2000 IU/mL, 2000-19 999 IU/mL, and ≥200 000 IU/mL, hepatocellular carcinoma incidence rates were 2-3 times higher in individuals with ALT 1·0-1·9 × ULN than in those with ALT concentrations less than the ULN. Individuals with persistently low HBV DNA concentrations (<2000 IU/mL) or persistently normal ALT concentrations across multiple assessments had slightly lower hepatocellular carcinoma incidence rates compared with those assessed by a single measurement. Our risk of bias assessment found 15 (21%) of 71 studies to be rated as good quality, 40 (56%) as fair quality, and 16 (23%) as poor quality. Interpretation: These findings, alongside the linked systematic review and meta-analysis of antiviral treatment efficacy, supported the 2024 WHO guidelines expansion of treatment criteria to include individuals with HBV DNA concentrations >2000 IU/mL and ALT concentrations above the ULN. For those with HBV DNA concentrations <2000 IU/mL and persistently normal ALT concentrations, treatment can be deferred.

• Ghorbani, Mahin; Kvedaraite, Agne; Al-Manei, Khaled; Too, Choon Boon; Cederberg, Susanne & Johannessen, Asgeir [Vis alle 12 forfattere av denne artikkelen] (2025). Oral Microbiome Diversity Matters on Nucleos(t)ide Analogue Cessation in Chronic Hepatitis B. Journal of Infectious Diseases. ISSN 0022-1899. doi: 10.1093/infdis/jiaf591. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Withdrawal of nucleos(t)ide analogue (NUC) therapy in hepatitis B e antigen (HbeAg)-negative chronic hepatitis B (CHB) may lead to functional cure in a subset of patients. Although gut microbiota is known to influence both CHB progression and treatment outcomes, the oral microbiome in NUC cessation remains unexplored. Methods This longitudinal study explored the oral microbiome in patients with CHB on NUC therapy &gt; 2 years having a planned NUC cessation. Oral microbiome composition was analyzed in 110 saliva samples across 7 time points from 18 HBeAg-negative patients with 36 months follow-up. Favorable outcome was defined as either HBsAg loss or decline of &gt; 1 log10 or sustained off-therapy HBV DNA level &lt; 2000 IU/mL during year 3. Hepatic flare was defined as alanine transaminase (ALT) &gt; 80 U/L or 2 × baseline level. Results The overall microbial composition remained stable during the study period. Patients with favorable outcome showed consistently higher alpha diversities (P &lt; .001) from baseline, with lower intersample variations across all time points (P &lt; .05), compared to unfavorable. Hepatitis B surface antigen (HBsAg), ALT, and aspartate transaminase (AST) correlated inversely with several Prevotella taxa and specific pathways (Spearman ρ &gt; −0.5, P &lt; .01). Unfavorable outcome and high HBsAg level correlated with opportunistic taxa Haemophilus parainfluenzae and Porphyromonas catoniae. Random forest model incorporating validated microbial markers predicting favorable versus unfavorable outcome achieved higher predictive performance than clinical markers alone (area under curve, 0.79 vs 0.66). Conclusions Our exploratory study suggests that oral microbiome profiling at NUC cessation in HBeAg-negative CHB could support prognostication of virological outcome. Clinical Trials Registration. NCT03681132.

• Rossvoll, Lasse Olsen; Mekonnen, Hailemichael Desalegn; Gudissa, Fikadu Girma; Birhanu, Dawit; Hussen, Ahmed & Cheneke, Waqtola [Vis alle 16 forfattere av denne artikkelen] (2025). Treatment of chronic hepatitis B in Ethiopia: 1-year results from a real-life, multicentre, prospective cohort study. The Lancet Global Health. ISSN 2572-116X. 13(11), s. e1914–e1923. doi: 10.1016/s2214-109x(25)00309-2. Fulltekst i vitenarkiv Vis sammendrag

  Background: In the global efforts to combat chronic hepatitis B virus (HBV) infection, the African continent is falling behind. Simplified treatment guidelines are recommended by WHO in low-income and middle-income countries, but it is unclear how this approach works in real life. We aimed to address this knowledge gap using a simplified treatment programme in Ethiopia. Methods: We did a prospective cohort study in four public hospitals in Ethiopia. We enrolled HIV-negative adults (age ≥18 years) with chronic HBV infection and applied simplified treatment criteria on the basis of clinical assessment, aspartate aminotransferase-to-platelet ratio index (APRI), alanine aminotransferase, and point-of-care HBV DNA. The primary endpoint was 1-year treatment outcome (active in care, dead, or lost to follow-up), and secondary endpoints were virological and biochemical treatment response. We used Cox proportional hazards regression models to identify predictors of death and logistic regression models to explore associating factors with decompensated cirrhosis. This study is registered with ClinicalTrials.gov, NCT02344498. Findings: Between Dec 8, 2021, and Dec 31, 2023, we enrolled 6010 participants (2953 [49·1%] female and 3057 [50·9%] male; median age 30 years [IQR 25-38]), of whom 1672 (27·8%) were eligible for treatment. 1138 (18·9%) started tenofovir disoproxil fumarate treatment before July 1, 2023, and were included in the 1-year analysis. 532 (46·7%) participants were active in care after 1 year, 58 (5·1%) died, and 508 (44·6%) were lost to follow-up. Of the participants active in care after 1 year, 321 (78·3%) of 410 had virological suppression (HBV DNA ≤10 IU/mL) and 289 (67·5%) of 428 had normal ALT (≤40 U/L). Independent predictors of death were decompensated cirrhosis (adjusted hazard ratio [HR] 8·74 [95% CI 5·01-15·27]) and age (per 1-year increment; adjusted HR 1·03 [1·01-1·05]). Decompensated cirrhosis was associated with male sex (adjusted odds ratio [OR] 1·68 [95% CI 1·17-2·40]), increasing age (per 1-year increment; adjusted OR 1·02 [1·01-1·03]), regular khat use (adjusted OR 1·54 [1·11-2·12]), and HBV DNA concentration greater than 200 000 IU/mL (adjusted OR 1·52 [1·10-2·11]). Interpretation: About half of the participants who initiated HBV treatment were still active in care after 1 year, and most of whom had virological and biochemical response to treatment. However, the high proportion lost to follow-up underscores the need for better strategies and tools to improve retention in HBV care.

• 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), s. 1–11. doi: 10.1111/jvh.70089. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Bugssa, Gessessew; Teklehaymanot, Tilahun; Medhin, Girmay; Nayagam, Shevanti; Johannessen, Asgeir & Berhe, Nega (2025). Prevalence and Factors Associated With Hepatitis B Virus Infection in Tigray Region, Northern Ethiopia. Journal of Viral Hepatitis. ISSN 1352-0504. 32(10). doi: 10.1111/jvh.70077. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Hepatitis B virus (HBV) infection is a significant public health concern, particularly in low‐income countries. This study investigates the prevalence and associated risk factors of HBV in Alamata district of Tigray region, northern Ethiopia, where the HBV vaccine was introduced in the childhood vaccination programme in 2007. A community‐based, cross‐sectional study was conducted from December 2019 to June 2020. Data were collected using structured questionnaires and hepatitis B surface antigen (HBsAg) was measured using a rapid diagnostic test. Logistic regression analyses were used to determine the associations between socio‐demographic, behavioural and health‐related variables and HBV infection. A total of 1853 individuals (54.2% females) were included in this study. The age ranged from 5 to 88 years, and the largest age group was from 5 to 14 years (32.0%). The overall HBV prevalence was 5.3% (95% confidence interval (CI) 4.3–6.3) with significant variability between age groups: 5–14 years 3.7%, 15–24 years 6.8%, 25–34 years 10.1%, 35–44 years 4.4%, 45–54 years 3.9% and 55 years and above 3.4%. Being in the 25–34 years age group (adjusted odds ratio (AOR) 4.1, 95% CI: 1.1–16.2, P= 0.042), reporting multiple sexual partners (AOR 4.0, 95% CI: 1.02–15.4, P= 0.047) and family history of hepatitis B (AOR 3.1, 95% CI: 1.2–8.2, P= 0.024) were independently associated with HBV infection. The prevalence of HBV infection was high in this region, underscoring the necessity for targeted public health strategies aimed at reducing transmission rates. Of note, the HBV prevalence was significantly lower among children born after the introduction of the HBV vaccine.

• Farah, Ahmed I.; Abdi, Hassan M.; Mohmed, Abdifatah J.; Abase, Suad M.; Ismail, Muna M. & Qalib, Jinaw M. [Vis alle 8 forfattere av denne artikkelen] (2025). Seroprevalence of transfusion transmitted infections among blood donors in Hargeisa, Somaliland: a retrospective study. BMC Public Health. 25(1), s. 1–7. doi: 10.1186/s12889-025-24411-7. Fulltekst i vitenarkiv Vis sammendrag

  Background: Blood transfusions save millions of lives each year, but are also associated with significant health risks, including transfusion-transmitted infections (TTIs). The World Health Organization recommends mandatory screening for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and syphilis prior to transfusion. This study presents the first screening results from a public blood bank in Somaliland. Method: Records from blood donors attending the blood bank of Hargeisa Group Hospital, Somaliland from January 2020 throughout December 2022 were reviewed retrospectively. Blood donations were screened using rapid diagnostic tests for HIV, HBsAg, anti-HCV and syphilis. Screening results and baseline demographic data were collected from all unique blood donors. Results: Among the 19,021 blood donors, 18,989 (99.8%) were male and the median age was 29 (interquartile range 25-35) years. A total of 310 (1.6%) individuals had one of the four TTIs screened for, of whom 226 (73%) were HBsAg positive. The seroprevalence of HIV was 0.1%; HBsAg 1.2%; anti-HCV 0.1%; and syphilis 0.3%. No co-infections were found. Conclusion: The most common TTI was hepatitis B virus infection. The reported seroprevalence of TTIs was low compared to other studies in the region.

• 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), s. 1105–1116. doi: 10.1080/23744235.2025.2530203. Fulltekst i vitenarkiv
• Razavi, Homie A.; Waked, Imam; Qureshi, Huma; Kondili, Loreta A.; Duberg, Ann-Sofi & Aleman, Soo [Vis alle 50 forfattere av denne artikkelen] (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), s. 329–347. doi: 10.1016/j.jhep.2025.01.013. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Desalegn, Hailemichael; Berhe, Nega; Rossvoll, Lasse Olsen; Girma, Fikadu; Brhane, Dawit & Hussen, Ahmed [Vis alle 8 forfattere av denne artikkelen] (2025). Time to Initiation of Hepatitis B Treatment is Reduced With the Use of the Xpert HBV Viral Load Kit. Open Forum Infectious Diseases. 12(5). doi: 10.1093/ofid/ofaf238. Fulltekst i vitenarkiv
• Voeller, Alexis S.; Johannessen, Asgeir; Abebe, Zebideru Zewdie; Adugna, Wegene; Gamkrelidze, Ivane & Seyoum, Eleni [Vis alle 14 forfattere av denne artikkelen] (2025). The Disease and Economic Burden of HBV and HCV in Ethiopia. Journal of Viral Hepatitis. ISSN 1352-0504. 32(2). doi: 10.1111/jvh.14053. Fulltekst i vitenarkiv Vis sammendrag

  As the second most populated country in Africa, Ethiopia needs public health measures to control diseases that impact its population. The goal of this study is to analyse disease burdens of HBV and HCV, while also highlighting their estimated associated costs for the country. A literature review and a Delphi process reflecting input of Ethiopian experts and the National Viral Hepatitis Technical Working Group were used to complement mathematical modelling to estimate HBV and HCV disease and economic burdens. Two scenarios were created for HCV: 2023 base and WHO elimination. For HBV, three scenarios were created: 2023 base, WHO elimination and universal birth dose. Using current country costs, each scenario was also examined through an economic lens. There were an estimated 7.6 million HBV infections in 2023. To impact transmission, a universal birth dose and pregnant women screening program would allow Ethiopia to vaccinate approximately 3.9 million infants annually, with a budget of $4.68 million USD, meeting the WHO prevalence elimination target (≤ 0.1% in ≤ 5-year-olds) by 2043. Ethiopia had an estimated 690,000 HCV infections in 2023. To achieve HCV elimination, the country would need to expand screening and treatment to 74,000 individuals annually with a peak budget of $12 million USD per year until 2032, decreasing to less than $2 million USD in 2035. Ethiopia can begin making steps towards elimination of HBV through expansion of birth dose vaccination. However, larger investments will be needed to scale-up treatment and diagnosis interventions for both diseases.

• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Vis alle 73 forfattere av denne artikkelen] (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), s. 249–259. doi: 10.1111/joim.13820. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Ismael, Nejib Yusuf; Usmael, Semir A.; Belay, Nega Berhe; Mekonnen, Hailemichael Desalegn; Johannessen, Asgeir & Orlien, Stian (2024). Chronic hepatitis B virus infection in Eastern Ethiopia: Clinical characteristics and determinants of cirrhosis. World Journal of Hepatology (WJH). ISSN 1948-5182. 16(7), s. 995–1008. doi: 10.4254/wjh.v16.i7.995. Fulltekst i vitenarkiv
• Arefaine, Mebrihit; Johannessen, Asgeir; Teklehaymanot, Tilahun; Mihret, Adane; Alemayehu, Dawit Hailu & Osman, Mahlet [Vis alle 8 forfattere av denne artikkelen] (2024). A prospective, multicenter study of hepatitis B birth-dose vaccine with or without hepatitis B immunoglobulin in preventing mother-to-child transmission of hepatitis B virus in Ethiopia. Vaccine. ISSN 0264-410X. 42(26). doi: 10.1016/j.vaccine.2024.126461. Fulltekst i vitenarkiv Vis sammendrag

  Background Historically, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) was considered uncommon in Africa, leading to a reluctant attitude to birth-dose HBV vaccination on the continent. As a randomized trial would be unethical, real-life data are needed to assess the effect of HBV birth-dose vaccine in Africa. Methods A multicenter, prospective, observational study of hepatitis B surface antigen (HBsAg)-positive pregnant women and their infants was carried out in Ethiopia, from January 2019 to May 2021. Pregnant women were screened for HBsAg and HIV as part of routine antenatal care and/or delivery, and HBsAg-positive HIV-negative pregnant women were included in the study. HBV birth-dose vaccine and hepatitis B immunoglobulin (HBIg) were recommended but not all newborns received it as it was not national policy. All infants, however, received the pentavalent HBV vaccine at 6, 10, and 14 weeks of age. Vaccination status was confirmed from delivery ward charts and infant vaccination certificates. Infants were tested for HBsAg at 9 months of age and a positive result was taken as evidence of MTCT. Findings Of 290 HBsAg-positive pregnant women, 168 mother/infant pairs returned for their 9-month follow-up visit and were included in this analysis. Two of 112 (1.8 %) infants who received birth-dose vaccine with HBIg, and 2 of 23 (8.7 %) who received birth-dose vaccine alone were HBsAg positive at nine months of age, compared to 8 of 33 (24.2 %) who received neither vaccine nor HBIg at birth (p = 0.002). High maternal viral load (>200,000 IU/ml; adjusted odds ratio [AOR] 10.4; 95 % confidence interval [CI] 1.2–92.1) and not receiving HBV birth-dose vaccine nor HBIg (AOR 29.2; 95 % CI 4.0–211.3) were independent predictors of MTCT. Interpretation Birth-dose HBV vaccine with or without HBIg significantly reduced the risk of MTCT of HBV in Ethiopia. Improved coverage of birth-dose HBV vaccine should be an urgent priority.

• Johannessen, Asgeir; Reikvam, Dag Henrik; Aleman, Soo; Berhe, Nega; Weis, Nina & Mekonnen, Hailemichael Desalegn [Vis alle 24 forfattere av denne artikkelen] (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), s. 434–445. doi: 10.1111/apt.18147. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Mekonnen, Hailemichael Desalegn; Xianchen, Yang; Yen, Yi-Syuan; Berhe, Nega; Brooke, Kenney & Siwo, Geoffrey [Vis alle 10 forfattere av denne artikkelen] (2024). Machine-learning methodologies to predict disease progression in chronic hepatitis B in Africa. Hepatology communications.. 8(12). doi: 10.1097/HC9.0000000000000584. Fulltekst i vitenarkiv Vis sammendrag

  Background: Little is known about the determinants of disease progression among African patients with chronic HBV infection. Methods: We used machine-learning models with longitudinal data to establish predictive algorithms in a well-characterized cohort of Ethiopian HBV-infected patients without baseline liver fibrosis. Disease progression was defined as an increase in liver stiffness to >7.9 kPa or initiation of treatment based on meeting the eligibility criteria. Results: Twenty-four of 551 patients (4.4%) experienced disease progression after a median follow-up time of 69 months. A random forest model based on a combination of available laboratory tests (standard hematology and biochemistry) demonstrated the best predictive properties with the AUROC ranging from 0.82 to 0.88. Conclusion: We conclude that combined metrics based on simple and available laboratory tests had good predictive properties and should be explored further in larger HBV cohorts.

• Minier, Nicolas; Guingane, Alice; Okeke, Edith; Sinkala, Edford; Johannessen, Asgeir & Andersson, Monique I. [Vis alle 27 forfattere av denne artikkelen] (2024). Development and evaluation of a simple treatment eligibility score (HEPSANET) to decentralise hepatitis B care in Africa: a cross-sectional study. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 9(4), s. 323–332. doi: 10.1016/S2468-1253(23)00449-1. Fulltekst i vitenarkiv
• Riches, Nicholas; Vinikoor, Michael; Guingane, Alice; Johannessen, Asgeir; Lemoine, Maud & Matthews, Philippa [Vis alle 23 forfattere av denne artikkelen] (2023). Hepatitis B in Africa Collaborative Network: cohort profile and analysis of baseline data. Epidemiology and Infection. ISSN 0950-2688. 151. doi: 10.1017/S095026882300050X. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, single-centre cohorts, with limited follow-up time. The Hepatitis B in Africa Collaborative Network (HEPSANET) was established in 2022 to harmonise the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next 5 years were agreed upon through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4,173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and the median age was 34 years (interquartile range 28–42). In total, 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg-positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region.

• Razavi-Shearer, Devin M.; Gamkrelidze, Ivane; Pan, Calvin Q.; Jia, Jidong; Berg, Thomas & Gray, Richard T. [Vis alle 269 forfattere av denne artikkelen] (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), s. 879–907. doi: 10.1016/S2468-1253(23)00197-8. Fulltekst i vitenarkiv
• Holmberg, Marte; Aass, Hans Christian; Dalgard, Olav; Samuelsen, Ellen; Sun, Dan & Björkström, Niklas K. [Vis alle 8 forfattere av denne artikkelen] (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. Fulltekst i vitenarkiv Vis sammendrag

  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 [Vis alle 56 forfattere av denne artikkelen] (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), s. 1–15. doi: 10.1186/s13054-022-04205-8. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Spearman, C. Wendy; Andersson, Monique I.; Bright, Bisi; Davwar, Pantong; Desalegn, Hailemichael & Guingane, Alice [Vis alle 20 forfattere av denne artikkelen] (2023). A new approach to prevent, diagnose, and treat hepatitis B in Africa. BMC Global and Public Health. doi: 10.1186/s44263-023-00026-1. Fulltekst i vitenarkiv Vis sammendrag

  There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.

• Woldemedihn, Gezahegn Mekonnen; Aberra, Hanna; Mekonnen, Hailemichael Desalegn; Berhe, Nega; Belay, Denekew Bitew & Rüegg, Corina Silvia [Vis alle 7 forfattere av denne artikkelen] (2023). Renal Safety of Long-term Tenofovir Disoproxil Fumarate Treatment in Patients With Chronic Hepatitis B. Open Forum Infectious Diseases. 10(8). doi: 10.1093/ofid/ofad404. Fulltekst i vitenarkiv Vis sammendrag

  Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individuals with chronic hepatitis B (CHB) are inconsistent. The current study aimed to assess the effect of long-term TDF treatment on renal outcomes in adult patients with CHB. Methods From a CHB cohort in Ethiopia, we included 233 patients treated with TDF and 126 untreated controls. Levels of creatinine and creatinine clearance over time were described in patients with and without TDF treatment. Linear mixed effects models with a treatment × time interaction were used to investigate the effect of TDF on creatinine and creatinine clearance. In treated patients only, change in creatinine and creatinine clearance was estimated separately in the first year as compared with subsequent years via linear mixed effects models. Results Median follow-up in the treated group was 51 months (IQR, 27–72), and 75% of patients were male (median age, 33 years; IQR, 26–40). Median follow-up in the untreated group was 69 months (IQR, 66–72), and 48% of participants were male (median age, 33 years; IQR, 27–41). We found no change in creatinine over time in TDF-treated patients as compared with a slight increase in untreated patients (P interaction = .003). There was a decrease in creatinine clearance over time in both groups, which was stronger in patients without TDF treatment (P interaction = .007). In TDF-treated patients, changes in creatinine and creatinine clearance occurred mainly within the first 12 months after treatment initiation. Conclusions This study showed no evidence of long-term renal toxicity of TDF treatment in patients with CHB.

• Isa, Yasir Shitu; Sicsic, Jonathan; Njuguna, Henry; Ward, John F.; Chakroun, Mohamed & El-Kassas, Mohamed [Vis alle 27 forfattere av denne artikkelen] (2023). Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers. BMC Medicine. 21(1). doi: 10.1186/s12916-023-02939-y. Fulltekst i vitenarkiv Vis sammendrag

  Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. Methods Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. Results A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. Conclusions African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.

• Johannessen, Asgeir; Stockdale, Alexander J.; Henrion, Marc; Okeke, Edith; Seydi, Moussa & Wandeler, Gilles [Vis alle 23 forfattere av denne artikkelen] (2023). Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa. Nature Communications. 14(1). doi: 10.1038/s41467-022-35729-w. Fulltekst i vitenarkiv Vis sammendrag

  In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5-20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.

• Mekonnen, Hailemichael Desalegn; Orlien, Stian; Aberra, Hanna; Mamo, Eyerusalem; Grude, Sine & Hommersand, Kristina [Vis alle 9 forfattere av denne artikkelen] (2023). Five-year results of a treatment program for chronic hepatitis B in Ethiopia. BMC Medicine. 21(1). doi: 10.1186/s12916-023-03082-4. Fulltekst i vitenarkiv Vis sammendrag

  In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa. Methods Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan–Meier method. Results In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular carcinoma-free survival was 99.0% in patients without cirrhosis at baseline, compared to 88.8% in patients with compensated cirrhosis, and 54.2% in patients with decompensated cirrhosis (p < 0.001). The risk of death was significantly higher in patients with decompensated cirrhosis at baseline (adjusted hazard ratio 44.6, 95% confidence interval 6.1–328.1) and in patients older than 40 years (adjusted hazard ratio 3.7, 95% confidence interval 1.6–8.5). Liver stiffness declined significantly after treatment initiation; the median change from baseline after 1, 3, and 5 years of treatment was − 4.0 kPa, − 5.2 kPa, and − 5.6 kPa, respectively. Conclusions This pilot program demonstrates the long-term benefits of CHB therapy in a resource-limited setting. The high mortality in patients with cirrhosis underscores the need for earlier detection of CHB and timely initiation of antiviral treatment in sub-Saharan Africa.

• Pan, Hongchao; Peto, Richard; Karim, Quarraisha Abdool; Alejandria, Marissa M.; Henao-Restrepo, Ana-Maria & Hernández-García, César [Vis alle 51 forfattere av denne artikkelen] (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), s. 1941–1953. doi: 10.1016/S0140-6736(22)00519-0. Fulltekst i vitenarkiv Vis sammendrag

  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).

• Vestad, Beate; Ueland, Thor; Lerum, Tøri Vigeland; Dahl, Tuva Børresdatter; Holm, Kristian & Barratt-Due, Andreas [Vis alle 37 forfattere av denne artikkelen] (2022). Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations. Journal of Internal Medicine. ISSN 0954-6820. 291(6), s. 801–812. doi: 10.1111/joim.13458. Fulltekst i vitenarkiv Vis sammendrag

  Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)

• Lerum, Tøri Vigeland; Maltzahn, Niklas; Aukrust, Pål; Trøseid, Marius; Nezvalova-Henriksen, Katerina & Kåsine, Trine [Vis alle 27 forfattere av denne artikkelen] (2021). Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9. Scientific Reports. 11, s. 1–12. doi: 10.1038/s41598-021-02547-x. Fulltekst i vitenarkiv Vis sammendrag

  The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.

• Kåsine, Trine; Riise, Anne Margarita Dyrhol; Barratt-Due, Andreas; Kildal, Anders Benjamin; Olsen, Inge Christoffer & Nezvalova-Henriksen, Katerina [Vis alle 39 forfattere av denne artikkelen] (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), s. 241–243. doi: 10.1111/joim.13377. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Johannessen, Asgeir; Mekasha, Bitsatab; Desalegn, Hailemichael; Aberra, Hanna; Stene-Johansen, Kathrine & Berhe, Nega (2021). Mother-to-Child Transmission of Hepatitis B Virus in Ethiopia. Vaccines. 9(5). doi: 10.3390/vaccines9050430. Fulltekst i vitenarkiv Vis sammendrag

  High viral load and positive hepatitis B e-antigen (HBeAg) results are risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV). In sub-Saharan Africa, little is known about the distribution of these risk factors, as well as early childhood HBV transmission. In this study, Ethiopian women aged 18-45 years with chronic hepatitis B were assessed for the presence of HBeAg and high viral load. Their children below 4 years of age were invited for assessment of viral markers, defining active HBV infection as a positive hepatitis B s-antigen (HBsAg) and/or detectable HBV DNA. In total, 61 of 428 HBV-infected women (14.3%) had a positive HBeAg result and/or a high viral load. Of note, 26 of 49 women (53.1%) with viral load above 200,000 IU/mL were HBeAg negative. Among 89 children born of HBV-infected mothers (median age 20 months), 9 (10.1%) had evidence of active HBV infection. In conclusion, one in seven women with chronic hepatitis B had risk factors for MTCT, and HBeAg was a poor predictor of high viral load. One in ten children born of HBV-infected women acquired HBV-infection despite completing their scheduled HBV vaccination at 6, 10 and 14 weeks of age.

• Barratt-Due, Andreas; Olsen, Inge Christoffer; Nezvalova-Henriksen, Katerina; Kåsine, Trine; Lund-Johansen, Fridtjof & Hoel, Hedda Benedicte [Vis alle 43 forfattere av denne artikkelen] (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), s. 1261–1269. doi: 10.7326/M21-0653. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Desalegn, Hailemichael; Chanie, Yemisrach; Shume, Paulos; Delil, Miftah; Gupta, Neil & Johannessen, Asgeir (2020). Assessment of Noninvasive Markers of Liver Fibrosis in Patients With Chronic Hepatitis C in Ethiopia. Clinical Liver Disease (CLD). 16(4), s. 168–172. doi: 10.1002/cld.1040. Fulltekst i vitenarkiv
• Woldemedihn, Gezahegn Mekonnen; Rueegg, Corina Silvia; Desalegn, Hailemichael; Aberra, Hanna; Berhe, Nega & Johannessen, Asgeir (2020). Validity of a point-of-care viral load test for hepatitis B in a low-income setting. Journal of Virological Methods. ISSN 0166-0934. 289. doi: 10.1016/j.jviromet.2020.114057. Fulltekst i vitenarkiv Vis sammendrag

  The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log10 to>7 log10 IU/mL were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log10 IU/mL higher viral load result of the Xpert kit; 4 samples differed by>1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94 %, specificity of 71 %, positive predictive value of 70 %, and negative predictive value of 95 %. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.

• Orlien, Stian; Ahmed, Tekabe Abdosh; Ismael, Nejib Yusuf; Berhe, Nega; Kran, Anne-Marte Bakken & Gundersen, Svein Gunnar [Vis alle 7 forfattere av denne artikkelen] (2020). Field performance of HBsAg rapid diagnostic tests in rural Ethiopia. Journal of Virological Methods. ISSN 0166-0934. 289. doi: 10.1016/j.jviromet.2020.114061. Fulltekst i vitenarkiv Vis sammendrag

  Point-of-care rapid diagnostic tests (POC-RDTs) are widely used to screen and diagnose hepatitis B virus (HBV) infection and are often the only available diagnostic tools in resource-limited settings. The aim of this study was to evaluate the validity of three hepatitis B surface antigen (HBsAg) POC-RDTs (Healgen®, Advanced Quality™ and Determine™) in an area with high prevalence of HBV in eastern Ethiopia. Results were compared with a commercial enzyme linked immunosorbent assay (ELISA) as gold standard. Quantification of HBsAg was performed in false negative samples. A total of 511 subjects were screened, of whom 81 (15.9%) were HBsAg-positive with the gold standard. All three POC-RDTs were positive in 65 of the 81 positive samples, yielding a sensitivity (95% confidence interval) of 80.2% (70.3-87.5) and a specificity of 99.8% (98.7-100 for Healgen® and Determine™; 98.6-100 for Advanced Quality™). False negatives were observed in 16 patients associated with low levels of HBsAg (median 1.5 IU/mL). All three POC-RDTs had reasonably high sensitivity and excellent specificity, but false negative results were observed in patients with low titres of HBsAg. Thus, these POC-RDTs might be useful to identify patients in need of HBV treatment, but cannot be recommended as blood donor screening tests.

• Desalegn, Hailemichael; Aberra, Hanna; Berhe, Nega; Medhin, Girmay; Mekasha, Bitsatab & Gundersen, Svein Gunnar [Vis alle 7 forfattere av denne artikkelen] (2019). Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study. BMC Gastroenterology. 19(74). doi: 10.1186/s12876-019-0993-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. Methods Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. Results Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26–276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23–173.48; p = 0.002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73–7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02–1.10; p = 0.007). Conclusions Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients.

• Al-Shudifat, Abdel-Ellah; Azab, Mohammed; Johannessen, Asgeir; Agraib, Lana & Tayyem, Reema (2019). Is the intake of antioxidants associated with risk of coronary artery disease? A Jordanian case-control study. Topics in Clinical Nutrition. ISSN 0883-5691. 34(4), s. 259–268. doi: 10.1097/TIN.0000000000000185. Fulltekst i vitenarkiv Vis sammendrag

  This study aimed to determine whether the intake of antioxidants was a risk factor for developing coronary artery disease. A total of 399 participants who underwent coronary angiography were included in the study, and patients with coronary artery disease (cases) were compared with patients with a normal coronary angiography (controls). Antioxidant consumption was higher in the control group than in the cases. Specifically, the controls had a higher consumption of foods rich in lutein, zeaxanthin, beta-carotene, and lycopene, but the difference did not reach statistical significance. The findings of the study suggest a possible beneficial association between coronary artery disease and the intake of dietary antioxidants

• Aberra, Hanna; Desalegn, Hailemichael; Berhe, Nega; Mekasha, Bitsatab; Medhin, Girmay & Gundersen, Svein Gunnar [Vis alle 7 forfattere av denne artikkelen] (2019). The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia. Journal of Hepatology. ISSN 0168-8278. 70(6), s. 1065–1071. doi: 10.1016/j.jhep.2019.01.037. Fulltekst i vitenarkiv
• Orlien, Stian; Sandven, Irene; Berhe, Nega; Ismael, Nejib Yusuf; Ahmed, Tekabe Abdosh & Stene-Johansen, Kathrine [Vis alle 9 forfattere av denne artikkelen] (2018). Khat chewing increases the risk for developing chronic liver disease: A hospital-based case-control study. Hepatology. ISSN 0270-9139. 68(1), s. 248–257. doi: 10.1002/hep.29809. Fulltekst i vitenarkiv
• Desalegn, Hailemichael; Aberra, Hanna; Berhe, Nega; Mekasha, Bitsatab; Stene-Johansen, Kathrine & Krarup, Henrik [Vis alle 9 forfattere av denne artikkelen] (2018). Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia. BMC Medicine. 16. doi: 10.1186/s12916-018-1229-x. Fulltekst i vitenarkiv Vis sammendrag

  Background The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. Methods At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. Results Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04–5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33–8.88). Conclusions This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. Trial registration NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.

• Azab, Mohammed; Al-Shudifat, Abdel-Ellah; Johannessen, Asgeir; Al-Shdaifat, Amjad; Agraib, Lana & Tayyem, Reema (2018). Are Risk Factors for Coronary Artery Disease Different in Persons with and Without Obesity? Metabolic Syndrome and Related Disorders. ISSN 1540-4196. 16(8), s. 440–445. doi: 10.1089/met.2017.0152. Fulltekst i vitenarkiv
• Orlien, Stian Magnus Staurung; Ismael, Nejib Yusuf; Ahmed, Tekabe Abdosh; Berhe, Nega; Lauritzen, Trine & Roald, Borghild [Vis alle 12 forfattere av denne artikkelen] (2018). Unexplained chronic liver disease in Ethiopia: a cross-sectional study. BMC Gastroenterology. 18(1). doi: 10.1186/s12876-018-0755-5. Fulltekst i vitenarkiv Vis sammendrag

  Background: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. Methods: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. Results: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25–40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. Conclusion: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.

• Orlien, Stian; Ahmed, Tekabe Abdosh; Ismael, Nejib Yusuf; Berhe, Nega; Lauritzen, Trine & Gundersen, Svein Gunnar [Vis alle 7 forfattere av denne artikkelen] (2018). High Seroprevalence of Autoantibodies Typical of Autoimmune Liver Disease in Eastern Ethiopia: Is Chewing of Khat (Catha edulis) a Triggering Factor? Canadian Journal of Gastroenterology and Hepatology. ISSN 2291-2789. s. 1–10. doi: 10.1155/2018/4980597. Fulltekst i vitenarkiv
• Al-Shudifat, Abdel-Ellah; Azab, Mohammed; Johannessen, Asgeir; Al-Shdaifat, Amjad; Agraib, Lana & Tayyem, Reema (2018). Elevated fasting blood glucose, but not obesity, is associated with coronary artery disease in patients undergoing elective coronary angiography in a referral hospital in Jordan. Annals of Saudi Medicine. ISSN 0256-4947. 38(2), s. 111–117. doi: 10.5144/0256-4947.2018.111. Fulltekst i vitenarkiv
• Aberra, Hanna; Gordien, Emmanuel; Desalegn, Hailemichael; Berhe, Nega; Medhin, Girmay & Mekasha, Bitsatab [Vis alle 11 forfattere av denne artikkelen] (2018). Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia. Liver international (Print). ISSN 1478-3223. 38(6), s. 1000–1009. doi: 10.1111/liv.13607. Fulltekst i vitenarkiv
• Desalegn, Hailemichael; Aberra, Hanna; Berhe, Nega; Gundersen, Svein Gunnar & Johannessen, Asgeir (2017). Are non-invasive fibrosis markers for chronic hepatitis B reliable in sub-Saharan Africa? Liver international (Print). ISSN 1478-3223. 37(10), s. 1461–1467. doi: 10.1111/liv.13393. Fulltekst i vitenarkiv
• Tayyem, Reema; Al-Shudifat, Abdel-Ellah; Johannessen, Asgeir; Bawadi, H A; AbuMweis, Suhad Sameer & Agraib, Lana [Vis alle 9 forfattere av denne artikkelen] (2017). Dietary patterns and the risk of coronary heart disease among Jordanians: A case–control study. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 28(3), s. 262–269. doi: 10.1016/j.numecd.2017.10.026. Fulltekst i vitenarkiv
• Al-Shudifat, Abdel-Ellah; Johannessen, Asgeir; Azab, Mohammed; Al-Shdaifat, Amjad; AbuMweis, Suhad Sameer & Agraib, Lana [Vis alle 7 forfattere av denne artikkelen] (2017). Risk factors for coronary artery disease in patients undergoing elective coronary angiography in Jordan. BMC Cardiovascular Disorders. 17(1). doi: 10.1186/s12872-017-0620-4. Fulltekst i vitenarkiv
• Al-Shudifat, Abdel-Ellah; Al-Shdaifat, Amjad; Al-Abdouh, Ahmad Ali; Aburoman, Mohammad Ibrahim; Otoum, Sara Mohammad & Sweedan, Amro Ghaleb [Vis alle 9 forfattere av denne artikkelen] (2017). Diabetes Risk Score in a Young Student Population in Jordan: A Cross-Sectional Study. Journal of Diabetes Research. ISSN 2314-6745. 2017. doi: 10.1155/2017/8290710. Fulltekst i vitenarkiv
• Aberra, Hanna; Desalegn, Hailemichael; Berhe, Nega; Medhin, Girmay; Stene-Johansen, Kathrine & Gundersen, Svein Gunnar [Vis alle 7 forfattere av denne artikkelen] (2017). Early experiences from one of the first treatment programs for chronic hepatitis B in sub-Saharan Africa. BMC Infectious Diseases. 17(1). doi: 10.1186/s12879-017-2549-8. Fulltekst i vitenarkiv
• Stene-Johansen, Kathrine; Yaqoob, Nadeem; Øverbø, Joakim; Aberra, Hanna; Desalegn, Hailemichael & Berhe, Nega [Vis alle 7 forfattere av denne artikkelen] (2016). Dry blood spots a reliable method for measurement of Hepatitis B viral load in resource-limited settings. PLOS ONE. 11(11). doi: 10.1371/journal.pone.0166201. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2015). Where we are with point-of-care testing. Journal of Viral Hepatitis. ISSN 1352-0504. 22(4), s. 362–365. doi: 10.1111/jvh.12385. Fulltekst i vitenarkiv
• Pettersen, Pernille; Brox, Ida Katarina; Naman, Ezra; Bruun, Johan N; Dyrhol-Riise, Anne Ma & Trøseid, Marius [Vis alle 7 forfattere av denne artikkelen] (2015). Antiretroviral treatment failure predicts mortality in rural Tanzania. International Journal of STD and AIDS. ISSN 0956-4624. 26(9), s. 633–639. doi: 10.1177/0956462414548460. Fulltekst i vitenarkiv
• Shao, Elichilia R.; Kifaro, Emmanuel G.; Chilumba, Innocent B.; Nyombi, Balthazar Melchior; Moyo, Sikhulile & Gaseitsiwe, Simani [Vis alle 10 forfattere av denne artikkelen] (2014). HIV-1 drug mutations in children from northern Tanzania. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 69(7), s. 1928–1932. doi: 10.1093/jac/dku087. Fulltekst i vitenarkiv
• Brantsæter, Arne; Johannessen, Asgeir; Holberg-Petersen, Mona; Sandvik, Leiv; Naman, Ezra & Kivuyo, Sokoine [Vis alle 9 forfattere av denne artikkelen] (2012). Cytomegalovirus viremia in dried blood spots is associated with an increased risk of death in HIV-infected patients: a cohort study from rural Tanzania. International Journal of Infectious Diseases. ISSN 1201-9712. 16(12), s. E879–E885. doi: 10.1016/j.ijid.2012.08.003. Fulltekst i vitenarkiv
• Kivuyo, Sokoine; Johannessen, Asgeir; Trøseid, Marius; Kasubi, Mabula Joseph; Gundersen, Svein Gunnar & Naman, Ezra [Vis alle 10 forfattere av denne artikkelen] (2011). p24 antigen detection on dried blood spots is a feasible and reliable test for infant HIV infection in rural Tanzania. International Journal of STD and AIDS. ISSN 0956-4624. 22(12), s. 719–721. doi: 10.1258/ijsa.2009.009382. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Naman, Ezra; Gundersen, Svein Gunnar & Bruun, Johan Nikolai (2011). Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania. BMC Infectious Diseases. 11. doi: 10.1186/1471-2334-11-190. Fulltekst i vitenarkiv Vis sammendrag

  HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART) in rural Africa is poorly understood. HIV-infected adults (≥15 years) who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine) on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men. We applied paired sample T-tests to compare hemoglobin levels before and one year after ART initiation, and logistic regression models to identify predictors of persistent anemia. At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4%) were anemic. Of the anemic patients, 254 (39.1%) had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P < 0.001); however, 39 patients (38.2%) were still anemic after 12 months of ART. Independent predictors of persistent anemia were mean cell volume in the lower quartile (<76.0 fL; Odds Ratio [OR] 4.34; 95% confidence interval [CI] 1.22-15.5) and a zidovudine-containing initial regimen (OR 2.91; 95% CI 1.03-8.19). Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.

• Johannessen, Asgeir; Garrido, Carolina; Zahonero, Natalia; Naman, Ezra & Mendoza, Carmen de (2011). HIV-1 drug resistance testing from dried blood spots collected in rural Tanzania using the ViroSeq HIV-1 Genotyping System. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 66(2), s. 260–264. doi: 10.1093/jac/dkq433. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2010). Dried blood spots in HIV monitoring: applications in resource-limited settings. Bioanalysis. ISSN 1757-6180. 2(11), s. 1893–1908. doi: 10.4155/BIO.10.120. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Holberg-Petersen, Mona; Løvgården, Gunilla; Naman, Ezra; Ormaasen, Vidar & Matee, Mecky I [Vis alle 8 forfattere av denne artikkelen] (2010). HIV type-1 drug resistance testing on dried blood spots is feasible and reliable in patients who fail antiretroviral therapy in rural Tanzania. Antiviral Therapy. ISSN 1359-6535. 15(7), s. 1003–1009. doi: 10.3851/IMP1660. Fulltekst i vitenarkiv Vis sammendrag

  Background: HIV type-1 (HIV-1) drug resistance testing is rarely available in resource-limited settings because of high costs and stringent requirements for storage and transport of plasma. Dried blood spots (DBS) can be a convenient alternative to plasma, but the use of DBS needs validation under field conditions. We assessed the performance of DBS in genotypic resistance testing of patients who failed first-line antiretroviral therapy (ART) in rural Tanzania. Methods: A total of 36 ART-experienced patients with viral loads >1,000 copies/ml (median 15,180 copies/ml [range 1,350?3,683,000]) and with various HIV-1 subtypes were selected for resistance testing. DBS were stored with desiccant at ambient temperature for a median of 29 days (range 8?89). Samples were amplified using an in-house reverse transcriptase-nested PCR method and sequenced using the ViroSeq? assay (Abbott Molecular, Des Plaines, IL, USA). DBS-derived genotypes were compared with genotypes from plasma. Results: Overall, 34 of 36 (94%) DBS specimens were successfully genotyped. In the protease region, of 142 polymorphisms found in plasma, 132 (93%) were also detected in DBS. In the reverse transcriptase region, of 57 clinically relevant mutations present in plasma, 51 (89%) were also detected in DBS. A total of 30 of 34 (88%) patients had identical resistance profiles to antiretroviral drugs in plasma and DBS. Conclusions: Genotyping was successful in the vast majority of DBS specimens stored at ambient temperature for up to 3 months, and there was high concordance between mutations found in DBS and plasma. Our study suggests that DBS can be a feasible and reliable tool to monitor HIV-1 drug resistance in patients on ART in resource-limited settings.

• Bratholm, Clara Sofie; Johannessen, Asgeir; Naman, Ezra; Gundersen, Svein Gunnar; Kivuyo, Sokoine & Holberg-Petersen, Mona [Vis alle 8 forfattere av denne artikkelen] (2010). Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 65(9), s. 1996–2000. doi: 10.1093/jac/dkq234. Fulltekst i vitenarkiv Vis sammendrag

  To assess long-term virological efficacy and the emergence of drug resistance in children who receive antiretroviral treatment (ART) in rural Tanzania. Haydom Lutheran Hospital has provided ART to HIV-infected individuals since 2003. From February through May 2009, a cross-sectional virological efficacy survey was conducted among children (<15 years) who had completed ≥6 months of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Genotypic resistance was determined in those with a viral load of >200 copies/mL. Virological response was measured in 19 of 23 eligible children; 8 of 19 were girls and median age at ART initiation was 5 years (range 2–14 years). Median duration of ART at the time of the survey was 40 months (range 11–61 months). Only 8 children were virologically suppressed (≤40 copies/mL), whereas 11 children had clinically relevant resistance mutations in the reverse transcriptase gene. The most frequent mutations were M184V (n = 11), conferring resistance to lamivudine and emtricitabine, and Y181C (n = 4), G190A/S (n = 4) and K103N (n = 4), conferring resistance to NNRTIs. Of concern, three children had thymidine analogue mutations, associated with cross-resistance to all nucleoside reverse transcriptase inhibitors. Despite widespread resistance, however, only one child experienced a new WHO stage 4 event and none had a CD4 cell count of <200 cells/mm3. Among children on long-term ART in rural Tanzania, >50% harboured drug resistance. Results for children were markedly poorer than for adults attending the same programme, underscoring the need for improved treatment strategies for children in resource-limited settings.

• Johannessen, Asgeir; Naman, Ezra; Kivuyo, Sokoine; Kasubi, Mabula J.; Holberg-Petersen, Mona & Matee, M. [Vis alle 9 forfattere av denne artikkelen] (2009). Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. BMC Infectious Diseases. 9, s. 8–8. Fulltekst i vitenarkiv Vis sammendrag

  Conclusion: Virological suppression rates were good up to 4 years after initiating ART in a rural Tanzanian hospital. However, drug resistance increased with time, and dual-class resistance was common, raising concerns about exhaustion of future antiretroviral drug options. This study might provide a useful forecast of drug resistance and demand for second-line antiretroviral drugs in rural Africa in the coming years.

• Johannessen, Asgeir; Garrido, Carolina; Zahonero, Natalia; Sandvik, Leiv; Naman, Ezra & Kivuyo, Sokoine [Vis alle 10 forfattere av denne artikkelen] (2009). Dried Blood Spots Perform Well in Viral Load Monitoring of Patients Who Receive Antiretroviral Treatment in Rural Tanzania. Clinical Infectious Diseases. ISSN 1058-4838. 49(6), s. 976–981. doi: 10.1086/605502. Fulltekst i vitenarkiv Vis sammendrag

  Conclusions. DBS, in combination with the NucliSENS EasyQ HIV-1 v1.2 asay, performed well in monitoring HIV viral loads in patients who received ART in rural Tanzania, although the sensitivity was reduced when viral burden was low. The use of DBS can simplify virological monitoring in resource-limited settings.

• Johannessen, Asgeir; Naman, Ezra; Kivuyo, Sokoine; Kasubi, Mabula; Holberg-Petersen, Mona & Matee, Mecky I [Vis alle 8 forfattere av denne artikkelen] (2009). Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. BMC Infectious Diseases. 9, s. 108–108. doi: 10.1186/1471-2334-9-108. Fulltekst i vitenarkiv Vis sammendrag

  Background Virological response to antiretroviral treatment (ART) in rural Africa is poorly described. We examined virological efficacy and emergence of drug resistance in adults receiving first-line ART for up to 4 years in rural Tanzania. Methods Haydom Lutheran Hospital has provided ART to HIV-infected patients since October 2003. A combination of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard first-line regimen. Nested in a longitudinal cohort study of patients consecutively starting ART, we carried out a cross-sectional virological efficacy survey between November 2007 and June 2008. HIV viral load was measured in all adults who had completed at least 6 months first-line ART, and genotypic resistance was determined in patients with viral load >1000 copies/mL. Results Virological response was measured in 212 patients, of whom 158 (74.5%) were women, and median age was 35 years (interquartile range [IQR] 29–43). Median follow-up time was 22.3 months (IQR 14.0–29.9). Virological suppression, defined as <400 copies/mL, was observed in 187 patients (88.2%). Overall, prevalence of ≥1 clinically significant resistance mutation was 3.9, 8.4, 16.7 and 12.5% in patients receiving ART for 1, 2, 3 and 4 years, respectively. Among those successfully genotyped, the most frequent mutations were M184I/V (64%), conferring resistance to lamivudine, and K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue mutations (TAMs), associated with cross-resistance to all nucleoside reverse transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both NRTIs and NNRTIs, was found in 64%. Conclusion Virological suppression rates were good up to 4 years after initiating ART in a rural Tanzanian hospital. However, drug resistance increased with time, and dual-class resistance was common, raising concerns about exhaustion of future antiretroviral drug options. This study might provide a useful forecast of drug resistance and demand for second-line antiretroviral drugs in rural Africa in the coming years.

• Johannessen, Asgeir; Garrido, Carolina; Zahonero, Natalia; Sandvik, Leiv; Naman, Ezra & Kivuyo, Sokoine [Vis alle 10 forfattere av denne artikkelen] (2009). Dried Blood Spots perform well in viral load monitoring of patients who receive antiretroviral treatment in rural Tanzania. Clinical Infectious Diseases. ISSN 1058-4838. 49, s. 976–981. doi: 10.1086/605502. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Trøseid, Marius & Calmy, Alexandra (2009). Dried blood spots can expand access to virological monitoring of HIV treatment in resource-limited settings. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 64(6), s. 1126–1129. doi: 10.1093/jac/dkp353. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Naman, Ezra; Ngowi, Bernard; Sandvik, Leiv; Matee, Mecky I & Aglen, Henry [Vis alle 8 forfattere av denne artikkelen] (2008). Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infectious Diseases. s. 52–52. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Naman, Ezra; Ngowi, Bernhard J; Sandvik, Leif; Matee, M. & Aglen, Henry E [Vis alle 8 forfattere av denne artikkelen] (2008). Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infectious Diseases. 8, s. 10–10. Fulltekst i vitenarkiv Vis sammendrag

  Conclusion: Mortality was found to be high, with the majority of deaths occurring within 3 months of starting ART. Anemia, thrombocytopenia and severe malnutrition were strong independent predictors of mortality. A prognostic model based on hemoglobin level appears to be a useful tool for initial risk assessment in resource-limited settings.

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• Buti, Maria; Rando‐Segura, Ariadna; Asmamaw, Asegedech; Romero, Judit & Johannessen, Asgeir (2026). From qHBsAg Correlation to Clinical Stratification—What Evidence Is Still Needed for Rapid HBsAg Time to Positivity? Authors' Reply. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. doi: 10.1111/apt.70977. Fulltekst i vitenarkiv
• El-Kassas, Mohamed; Shousha, Hend & Johannessen, Asgeir (2026). Africa must not be left out of the hepatitis B cure era. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/s2468-1253(26)00024-5. Fulltekst i vitenarkiv
• Malme, Kristian Braathen; Berhe, Nega; Hunduma, Fufa; Desalegn, Hailemichael & Johannessen, Asgeir (2025). Decentralization of hepatitis B care in sub-Saharan Africa: study protocol for a prospective cohort assessing three models of care in rural Ethiopia. doi: 10.1186/s12913-025-13340-1. Fulltekst i vitenarkiv Vis sammendrag

  Background: Improving treatment uptake among people with chronic hepatitis B (CHB) infection who live outside urban centres is crucial to achieving the World Health Organization (WHO) elimination targets. Furthermore, as the number of deaths due to hepatitis B in Africa is rising, there is a need for new models of decentralized care adapted to the local context. The main aim of this study is to compare three different models of decentralized care for CHB treatment in Ethiopia, both from a clinical perspective and an implementation perspective. Methods: This will be prospective cohort study comparing three models of decentralized care for the management of CHB in Ethiopia. The first model (“standard model”) utilizes the current WHO guidelines for CHB management. The second model (“simplified model”) offers treatment to all individuals with CHB except those with a completely normal baseline assessment, and the third model (“test-and-treat model”) provides treatment to all individuals with CHB. The study will enroll 4,500 individuals with CHB over a one-year period across six study sites in Ethiopia. All patients will be followed up for 3 years, and the primary outcome is death or liver failure. The three models will be compared using a Cox proportional hazards regression model adjusting for potential confounders. Additionally, we will design adequate implementation strategies to address barriers and facilitators to implementation. We will design, implement and evaluate a policy toolbox that will ensure local adoption and implementation, using a co-creation approach, bringing together policymakers, politicians, healthcare personnel and patients, to come up with adequate policy implementation strategies for their contexts. Discussion: From a public health perspective, identifying a simple, feasible and effective model of decentralized CHB care would be a key step to reduce liver-related mortality on the African continent. This study may have important policy implications and is expected to inform national and international hepatitis B elimination efforts in low- and middle income countries (LMICs).

• Johannessen, Asgeir (2025). Early antiviral therapy in adults with moderate to highly viraemic chronic hepatitis B. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/S2468-1253(25)00008-1. Fulltekst i vitenarkiv
• Desalegn, Hailemichael; Rossvoll, Lasse Olsen; Hunduma, Fufa; Berhe, Nega & Johannessen, Asgeir (2025). Hepatitis B treatment in Africa: learning points from a scale-up programme in Ethiopia. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 10, s. 190–192. doi: 10.1016/S2468-1253(24)00396-0. Fulltekst i vitenarkiv
• Johannessen, Asgeir & Midgard, Håvard (2024). Hepatitt-test til alle. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(9). doi: 10.4045/tidsskr.24.0365. Fulltekst i vitenarkiv
• Minier, Nicolas; Johannessen, Asgeir; Sombié, Roger; Lemoine, Maud & Shimakawa, Yusuke (2024). The HEPSANET score to assess treatment eligibility of chronic hepatitis B in Africa – Authors' reply. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 9(7), s. 589–590. doi: 10.1016/S2468-1253(24)00123-7. Fulltekst i vitenarkiv
• 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), s. 404–405. doi: 10.1111/apt.18439. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2023). Is it time for a paradigm shift in treatment guidelines for chronic hepatitis B? The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 8(9). doi: 10.1016/S2468-1253(23)00236-4. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Gebremedhin, Lia Tadesse & Desalegn, Hailemichael (2022). New WHO hepatitis B treatment guidelines: look to Ethiopia. The Lancet Global Health. ISSN 2572-116X. 10(12), s. e1711–e1712. doi: 10.1016/S2214-109X(22)00420-X. Fulltekst i vitenarkiv
• Orlien, Stian; Berhe, Nega; Morgan, Marsha Yvonne & Johannessen, Asgeir (2019). Khat-related liver disease in sub-Saharan Africa: neglected, yet important. The Lancet Global Health. ISSN 2572-116X. 7(3), s. e310–e310. doi: 10.1016/S2214-109X(18)30527-8. Fulltekst i vitenarkiv
• Johannessen, Asgeir; Aberra, Hanna; Desalegn, Hailemichael; Gordien, Emmanuel & Berhe, Nega (2019). A novel score to select patients for treatment in chronic hepatitis B: Results from a large Ethiopian cohort. Journal of Hepatology. ISSN 0168-8278. 71(4), s. 840–841. doi: 10.1016/j.jhep.2019.04.006. Fulltekst i vitenarkiv
• Desalegn, Hailemichael & Johannessen, Asgeir (2017). Response to Non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan Africa. Liver international (Print). ISSN 1478-3223. 37(11), s. 1739–1739. doi: 10.1111/liv.13425. Fulltekst i vitenarkiv
• Johannessen, Asgeir & Lemoine, Maud (2015). Is aspartate aminotransferase-to-platelet ratio index a reliable tool in human immunodeficiency virus patients in Africa? Liver international (Print). ISSN 1478-3223. 35(8), s. 2059–2059. doi: 10.1111/liv.12793. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2011). Are men the losers of the antiretroviral treatment scale-up? AIDS (London). ISSN 0269-9370. 25(9), s. 1225–1226. doi: 10.1097/QAD.0b013e32834403b8. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2011). Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital-author's response. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 66(4), s. 957–958. doi: 10.1093/jac/dkr042. Fulltekst i vitenarkiv
• Trøseid, Marius & Johannessen, Asgeir (2010). Et skritt i riktig retning. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 130(22), s. 2223–2223. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2010). Quantification of HIV-1 RNA on dried blood spots. AIDS (London). ISSN 0269-9370. 24(3), s. 475–476. doi: 10.1097/QAD.0b013e3283365383. Fulltekst i vitenarkiv
• Johannessen, Asgeir (2011). Antiretroviral treatment of HIV/AIDS in rural Tanzania : Long-term outcome and simplified monitoring tools. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  The scale-up of antiretroviral treatment (ART) of HIV/AIDS in resource-limited settings has been one of the largest public health operations of our time, and by the end of 2009 more than 5 million people were receiving ART in low- and middle-income countries. Although several studies on ART efficacy in Africa have been published, the majority have been carried out in larger cities and usually with short follow-up time. To date, there is a paucity of research from rural settings, which often face additional challenges, such as shortages of health workers, transport difficulties and other logistical constraints. In the first part of the present study we reported long-term clinical and virological outcomes of ART in a rural hospital in Tanzania. In the second part of this study we addressed the lack of field-friendly tools for virological monitoring of patients on ART. Viral load and resistance testing, as recommended in high-income countries, are rarely available in resource-limited settings due to high costs and stringent requirements for storage and transport of plasma. Consequently, treatment failure in such settings usually passes unnoticed until patients develop severe immunodeficiency, at which stage widespread resistance is likely. Dried blood spots (DBS) are easy to collect and store, and can be a convenient alternative to plasma. Unlike plasma, DBS can be stored and shipped at ambient temperature, thus avoiding the need for cold chain and speedy transport to the laboratory. In our study, under field conditions in rural Tanzania, we assessed the performance of DBS in virological monitoring of patients on ART. Haydom Lutheran Hospital has provided ART to HIV-infected patients since 2003. A combination of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard first-line regimen, in accordance with WHO and Tanzanian guidelines. All patients who started ART from October 2003 through December 2007 were included in a longitudinal cohort study. Standard techniques of survival analysis were used to estimate mortality and identify predictors of mortality. Virological efficacy and emergence of drug resistance was assessed in patients who had completed at least 6 months of first-line ART. Viral load and resistance results obtained with a standard plasma-based method were compared with results obtained with the use of DBS. Paper I and II were epidemiological studies. We found a high mortality in this cohort, particularly the first months after initiating ART: estimated mortality was 19.2%, 29.0% and 41.7% after 3, 12 and 36 months, respectively. Anemia, malnutrition and thrombocytopenia were strong and independent predictors of mortality. A prognostic model based on hemoglobin level appeared to be a useful tool for initial risk assessment: estimated one year mortality was 3.7% in patients without anemia compared to 55.2% in those with severe anemia (<8 g/dL). Among patients who survived the first 6 months and remained in care, however, we found good long-term virological efficacy: viral suppression (<400 copies/mL) was observed in 187 of 212 (88.2%) patients after a median follow-up time of 22.3 months. In total, 18 patients harbored at least one clinically significant drug-resistance mutation, of whom 5 had thymidine analogue mutations associated with broad cross-resistance to nucleoside reverse transcriptase inhibitors. Although the overall prevalence of drug resistance was relatively low, it increased with time and reached approximately 15% after 3-4 years on ART. Paper III and IV were laboratory studies. First, we compared the viral load levels in 98 plasma-DBS pairs from patients on ART. In a linear regression model there was a strong correlation, with an R2 value of 0.75, between the two specimen types. Viral loads were on average slightly higher in plasma than DBS, but the mean difference was only 0.04 log10 copies/mL. However, DBS had reduced sensitivity to detect HIV-1 RNA in samples with low-level viraemia (<3000 copies/mL). Subsequently, we compared genotypic resistance results from DBS with those of plasma in 36 ART-experienced individuals with treatment failure (viral load >1000 copies/mL). Overall, 34 of 36 (94%) DBS specimens were successfully genotyped, and there was high concordance between mutations found in plasma and DBS. Thirty of 34 (88%) patients had identical resistance profiles to antiretroviral drugs in plasma and DBS. In conclusion, we found a high early mortality in this cohort. Simple laboratory markers, especially hemoglobin level, appeared to be useful for initial risk assessment, and can be of particular use in settings without access to CD4 cell counts. Long-term virological efficacy rates were favorable, and drug resistance appeared to develop at the same rate as in high-income countries. Finally, we found that the use of DBS was a feasible and reliable option for viral load and resistance testing, and we believe that DBS could simplify virological monitoring in resource-limited settings.

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