title: Virus-related liver cirrhosis: molecular basis and therapeutic options.
abstract: Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
authors.affiliation: Ji Lin, Jian-Feng Wu, Qi Zhang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Lin
authors.affiliation: Ji Lin, Jian-Feng Wu, Qi Zhang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Ji Lin, Jian-Feng Wu, Qi Zhang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Ji Lin, Jian-Feng Wu, Qi Zhang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Ji Lin, Jian-Feng Wu, Qi Zhang, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Cao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D005838:Genotype; D016174:Hepacivirus; D055166:Hepatic Stellate Cells / Q000166:cytology; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000821:virology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology*; D009154:Mutation; D012038:Regeneration; D012254:Ribavirin / Q000627:therapeutic use; D013234:Stem Cells / Q000166:cytology; D014779:Virus Replication; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Antiviral therapy; Evolution; Hepatic stellate cells; Hepatitis B virus; Hepatitis C virus; Immune cells; Liver cirrhosis; Signaling pathway