Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders

Dig Dis Sci. 2016 Jun;61(6):1744-56. doi: 10.1007/s10620-016-4122-5. Epub 2016 Apr 8.

Abstract

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.

Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.

Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.

Results: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.

Conclusions: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

Keywords: Cirrhosis; Hepatitis C; Hepatitis C therapy; Hepatocellular carcinoma; Survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cohort Studies
  • Female
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Liver Cirrhosis / etiology*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use
  • United States / epidemiology
  • United States Department of Veterans Affairs

Substances

  • Interferon-alpha
  • Ribavirin