Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C†

Abstract

The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P ‫؍‬ .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed. (HEPATOLOGY 2005;41:617-625.)

The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function

“…These two opposite pathogenic events have both been associated with an increase in virus-specific T-cell immunity, but it remains difficult to understand why changes in T-cell immunity can be associated with either an increase or decrease in disease activity (11,28,42,43,50,53,57).…”

Preservation of Intrahepatic Hepatitis C Virus (HCV)–Specific CD4+T Cell Responses despite Global Loss of CD4+T Cells in HCV/HIV Coinfection

“…Freshly isolated PBMCs (200,000/well) were cultured with HCV protein antigens SOD (superoxide dismutase)-c22 (core), SOD-c100 (NS4), SOD-c200 (NS3 and NS4), SOD-c25 (core, NS3, and NS4), and SOD-NS5, as well as control SOD alone (all 10 mg/mL; gifts of Dr. M. Houghton, Chiron Corp.) and Candida and tetanus proteins as described elsewhere [14] at 37ЊC (5% CO 2 ). Recombinant human interleukin (rhIL-2; 20 U/mL) was added on day 6 of culture.…”

Progression of Fibrosis during Chronic Hepatitis C Is Associated with Rapid Virus Evolution

“…Using single-stranded conformational polymorphism, investigators have found higher viral complexity associated with higher alanine aminotransferase (ALT) (54) and advanced fi-brosis (18) in some studies but not in others (10,22,27,29,38). Rather than use a gel shift assay, some studies have used nucleotide sequencing to study the viral quasispecies.…”