title: 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.
authors.affiliation: Center for Infectious Disease and Vaccine Research and Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. alan.rothman@umassmed.edu
authors.forename: Alan Lee
authors.initials: AL
authors.lastname: Rothman
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Polyak
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Peter F
authors.initials: PF
authors.lastname: Malet
authors.forename: Ming
authors.initials: M
authors.lastname: Chang
authors.forename: David R
authors.initials: DR
authors.lastname: Gretch
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Sullivan
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Margaret James
authors.initials: MJ
authors.lastname: Koziel
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral