Apoptosis in hepatitis C.
The apoptotic process appears to be a host defence mechanism against viral infections and tumourigenesis. However, many viral genomes encode proteins, which repress apoptosis so as to escape from immune attack by the host. Therefore, virus-host interactions may determine viral persistence, extent and severity of liver inflammation and possibly viral hepatocarcinogenesis. Apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C. Pathomorphologic features of increased apoptosis include shrinkage and fragmentation of nuclei/cytoplasm in piecemeal necrosis areas, acidophilic bodies, and focal cell dropout in the liver lobule. The hepatitis C virus (HCV) core protein exhibits both proapoptotic or antiapoptotic actions. Modulation of apoptosis may involve binding of HCV core protein to the intracellular signal transducing portion of death receptors and displacement of signalling molecules. Apoptosis may occur in the absence of significant transaminase elevation, thereby explaining the lack of correlation between biochemical activity and liver cell histological injury. Monitoring caspase activation might provide a reliable tool to estimate the efficacy of HCV therapy, and might open challenging therapeutic strategies in HCV infection. The antiviral effect of interferon may be mediated through induction of apoptosis. Lastly, administration of the antiapoptotic ursodeoxycholic acid in HCV infection is compatible with the notion that apoptosis may represent a mechanism for viral shedding rather than for viral elimination, thereby raising the concept that inhibition of apoptosis could ameliorate hepatitis C.
Kountouras
J
J
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. jannis@med.auth.gr
Zavos
C
C
Chatzopoulos
D
D
D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects; D006526:Hepatitis C / Q000209:etiology / Q000503:physiopathology*; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D014758:Viral Core Proteins / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D000998:Antiviral Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014758:Viral Core Proteins; D019014:fas Receptor; D014580:Ursodeoxycholic Acid; D007372:Interferons; D020169:Caspases