Outcome of sustained virological responders with histologically advanced chronic hepatitis C

Hepatology. 2010 Sep;52(3):833-44. doi: 10.1002/hep.23744.

Abstract

Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR.

Conclusion: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC.

Trial registration: ClinicalTrials.gov NCT00006164.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / epidemiology
  • Cohort Studies
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Hepatitis C, Chronic / diagnosis*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / mortality
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Liver / pathology
  • Liver Neoplasms / epidemiology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Prognosis
  • Prospective Studies
  • Recombinant Proteins
  • Recurrence
  • Ribavirin / therapeutic use*
  • Risk Factors
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome
  • United States

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00006164

Grant support