Original article
Pancreas, biliary tract, and liver
Antiviral Therapy for Chronic Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma in a US Population

https://doi.org/10.1016/j.cgh.2013.09.062Get rights and content

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.

Section snippets

CHeCS Cohort

The CHeCS investigation follows the guidelines of the US Department of Health and Human Services regarding the protection of human subjects. The protocol was approved and is renewed annually by the institutional review board at each participating site.

The CHeCS project’s methods have been summarized previously.10 Briefly, electronic administrative data and electronic health records of patients 18 years or older who had received any health services between January 1, 2006 and December 31, 2010

Results

We found 4158 chronic HBV infection candidates based on electronic criteria, of which 2775 were confirmed to have chronic HBV infection based on chart abstraction to date. Of the 2775 patients, 99 were coinfected with HCV, and 4 had received a diagnosis of HCC more than 60 days before the diagnosis of HBV; these patients were excluded. This left 2671 patients in the study cohort. The earliest HBV diagnosis was in 1992, and median diagnosis year was 2005 (interquartile range, 2002–2007). Median

Discussion

In this large American community-based cohort, a history of antiviral therapy for chronic HBV infection was associated with a reduction in the risk of HCC over a median of 5 years. To our knowledge, this analysis is the only US-based study to show such a benefit, and the large size and diversity of the cohort (geographic, clinical, and racial) and long duration of follow-up extend the generalizability of similar findings observed in smaller, more homogenous populations.

Given that persistent

Acknowledgments

The authors thank Patricia A. French of Left Lane Communications and Karen Staman of Karen Staman Writing and Editing for writing and editing assistance with support from the Henry Ford Health System during development of the manuscript.

References (19)

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The CHeCS Investigators are listed in the Appendix.

Conflicts of interest This author discloses the following: Stuart C. Gordon receives grant and research support from AbbVie Pharmaceuticals, Bristol-Myers Squibb, Gilead Pharmaceuticals, GlaxoSmithKline, Intercept Pharmaceuticals, Merck, and Vertex Pharmaceuticals. He is also a consultant for Amgen, Bristol-Myers Squibb, CVS Caremark, Gilead Pharmaceuticals, Merck, Novartis, and Vertex and is on the Data Monitoring Board for Janssen Pharmaceuticals. The remaining authors disclose no conflicts.

Funding The CHeCS project is funded by the CDC Foundation, which receives grants from AbbVie; Genentech, a Member of the Roche Group; Janssen Pharmaceutical Companies of Johnson & Johnson; and Vertex Pharmaceuticals. Past funders include Bristol-Myers-Squib. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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