Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population

Clin Gastroenterol Hepatol. 2014 May;12(5):885-93. doi: 10.1016/j.cgh.2013.09.062. Epub 2013 Oct 6.


Background & aims: Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers.

Methods: We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence.

Results: Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL.

Conclusions: In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.

Keywords: Alanine Aminotransferase; Fibrosis; Liver Cancer; Tumor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Biostatistics
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / prevention & control
  • Cohort Studies
  • Female
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Incidence
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / prevention & control
  • Male
  • Middle Aged
  • Risk Assessment
  • Time Factors
  • United States / epidemiology
  • Young Adult


  • Antiviral Agents