{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:33:11Z","timestamp":1791253991005,"version":"4.1.0"},"reference-count":178,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:00:00Z","timestamp":1668816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH-NIGMS","award":["R35GM124915"],"award-info":[{"award-number":["R35GM124915"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:p>Viral hepatitis is a leading cause of liver morbidity and mortality globally. The mechanisms underlying acute infection and clearance, versus the development of chronic infection, are poorly understood. In vitro models of viral hepatitis circumvent the high costs and ethical considerations of animal models, which also translate poorly to studying the human-specific hepatitis viruses. However, significant challenges are associated with modeling long-term infection in vitro. Differentiated hepatocytes are best able to sustain chronic viral hepatitis infection, but standard two-dimensional models are limited because they fail to mimic the architecture and cellular microenvironment of the liver, and cannot maintain a differentiated hepatocyte phenotype over extended periods. Alternatively, physiomimetic models facilitate important interactions between hepatocytes and their microenvironment by incorporating liver-specific environmental factors such as three-dimensional ECM interactions and co-culture with non-parenchymal cells. These physiologically relevant interactions help maintain a functional hepatocyte phenotype that is critical for sustaining viral hepatitis infection. In this review, we provide an overview of distinct, novel, and innovative in vitro liver models and discuss their functionality and relevance in modeling viral hepatitis. These platforms may provide novel insight into mechanisms that regulate viral clearance versus progression to chronic infections that can drive subsequent liver disease.<\/jats:p>","DOI":"10.1055\/a-1981-5944","type":"journal-article","created":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T23:31:10Z","timestamp":1668900670000},"page":"031-049","source":"Crossref","is-referenced-by-count":4,"title":["Physiomimetic In Vitro Human Models for Viral Infection in the Liver"],"prefix":"10.1055","volume":"43","author":[{"given":"Dennis","family":"McDuffie","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Helm","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Baumert","sequence":"additional","affiliation":[{"name":"Inserm Research Institute for Viral and Liver Diseases, University of Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, Florida"},{"name":"Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, Florida"},{"name":"Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, Florida"},{"name":"Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"issue":"07","key":"ref1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nri2802","article-title":"Immunity and immunopathology to viruses: What decides the outcome?","volume":"10","author":"B T Rouse","year":"2010","journal-title":"Nat Rev 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