Brian K. Chung

• Fretheim, Håvard Halland; Chung, Brian K.; Didriksen, Henriette; Bækkevold, Espen Sønderaal; Midtvedt, Øyvind & Brunborg, Cathrine [Show all 18 contributors for this article] (2020). Fecal Microbiota Transplantation in Systemic Sclerosis: A Double-Blind, Placebo-Controlled Randomized Pilot Trial. PLOS ONE. ISSN 1932-6203. 15:e0232739(5), p. 1–14. doi: 10.1371/journal.pone.0232739. Full text in Research Archive
• Tucker, Lori B.; Lamot, Lovro; Niemietz, Iwona; Chung, Brian K.; Cabral, David A. & Houghton, Kristin [Show all 12 contributors for this article] (2019). Complexity in unclassified auto-inflammatory disease: A case report illustrating the potential for disease arising from the allelic burden of multiple variants. Pediatric Rheumatology. ISSN 1546-0096. 17:70, p. 1–7. doi: 10.1186/s12969-019-0374-x.
• Chung, Brian K.; Karlsen, Tom Hemming & Folseraas, Trine (2017). Cholangiocytes in the pathogenesis of primary sclerosing cholangitis and development of cholangiocarcinoma. Biochimica et Biophysica Acta - Molecular Basis of Disease. ISSN 0925-4439. 1864(4), p. 1390–1400. doi: 10.1016/j.bbadis.2017.08.020. Show summary

  Primary sclerosing cholangitis (PSC) is an idiopathic cholangiopathy strongly associated with inflammatory bowel disease (IBD) and characterized by cholestasis, chronic immune infiltration and progressive fibrosis of the intrahepatic and extrahepatic bile ducts. PSC confers a high risk of cholangiocarcinoma (CCA) with PSC-CCA representing the leading cause of PSC-associated mortality. PSC-CCA is derived from cholangiocytes and associated progenitor cells - a heterogeneous group of dynamic epithelial cells lining the biliary tree that modulate the composition and volume of bile production by the liver. Infection, inflammation and cholestasis can trigger cholangiocyte activation leading to an increased expression of adhesion and antigen-presenting molecules as well as the release of various inflammatory and fibrogenic mediators. As a result, activated cholangiocytes engage in a myriad of cellular processes, including hepatocellular proliferation, apoptosis, angiogenesis and fibrosis. Cholangiocytes can also regulate the recruitment of immune cells, mesenchymal cells, and endothelial cells that participate in tissue repair and destruction in settings of persistent inflammation. In PSC, the role of cholangiocytes and the mechanisms governing their transformation to PSC-CCA are unclear however localization of disease suggests that cholangiocytes are a key target and potential regulator of hepatobiliary immunity, fibrogenesis and tumorigenesis. Herein, we summarize mechanisms of cholangiocyte activation in PSC and highlight new insights into disease pathways that may contribute to the development of PSC-CCA. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen

• Chung, Brian K. & Karlsen, Tom Hemming (2017). Genetic Discoveries Highlight Environmental Factors as Key Drivers of Liver Disease. Digestive Diseases. ISSN 0257-2753. 35(4), p. 323–333. doi: 10.1159/000456583. Show summary

  Background: Over the last 50 years, genetic studies have uncovered a spectrum of rare and common alleles that confer susceptibility to both Mendelian and complex forms of liver disease. For disorders of Mendelian inheritance, identification of the causal variants has demonstrated that common environmental exposures can elicit severe liver pathogenesis in predisposed individuals. Specific environmental triggers for complex liver disorders are largely unknown; however, large-scale association studies indicate that environmental triggers are the predominant factors in driving liver pathophysiology. Key Messages: In Mendelian liver disorders, a single rare variant of major effect is often responsible for disease development. Gene-sequencing technologies have greatly facilitated the discovery of causal variants for Mendelian diseases and are increasingly utilized in molecular and clinical genetics for diagnostic and counselling purposes. By contrast, genetic susceptibility for complex liver disorders is heterogeneous, as many different genes acting on multiple distinct pathways influence disease onset and severity. Risk variants for complex liver disorders are relatively common, typically of small effect size and detected by genome-wide association studies (GWAS), which compare the genetic variation of specific loci using thousands of patients and healthy controls. Thus far, GWAS have detected dozens of unique and overlapping risk alleles for complex liver disease, but these account for less than a quarter of the overall disease liability. These observations emphasize that environmental exposures on a background of genetic predisposition are significant drivers of liver pathophysiology. Rare variants of large effect size, undetectable by GWAS, may also affect the development of complex disease on a case-to-case basis but evidence for such a scenario remains to be determined. Conclusions: Genetic technologies have identified numerous risk genes for Mendelian and complex liver disorders transforming disease recognition. For complex liver disorders, deciphering the interplay between genetic risk and environment determinants remains a significant challenge for unlocking the development of novel and personalized interventions.

• Chung, Brian K. & Hirschfield, Gideon M. (2017). Immunogenetics in primary sclerosing cholangitis. Current Opinion in Gastroenterology. ISSN 0267-1379. 33(2), p. 93–98. doi: 10.1097/MOG.0000000000000336.

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