Antiviral Treatment Reduces Risk of Cirrhosis, Hepatocellular Cancer and Mortality among Veterans, Irrespective of Age

BACKGROUND:
Chronic hepatitis C is a common and progressive condition. Based on the known hepatitis C virus (HCV) acquisition time (i.e., 1960s to 1980s) and age of acquisition (i.e., 20 to 40 years) of most infected persons in the U.S., the proportion of elderly Americans with chronic hepatitis C is expected to increase over time. Moreover, it is estimated that at least one-third of patients with this condition will progress to advanced fibrosis and cirrhosis – a subset at high risk for subsequent complications, including hepatocellular cancer (HCC). This retrospective cohort study examined the association between age subgroups (20-49, 50-64, 65-85 years or "elderly") and risk of cirrhosis, HCC, or death among Veterans (n=161,744) who tested positive for HCV between October 1999 and December 2009, including those who received treatment in VA facilities. Primary outcomes were new cases of cirrhosis and/or HCC that were first recorded more than a year after the HCV index date. Investigators also examined rates of death, as well as potential confounders including: period of service (i.e., WWII, Vietnam era, post-Vietnam era), demographics, comorbidities (i.e., diabetes, obesity, HIV infection, hepatitis B virus infection), and receipt and success of HCV treatment and treatment-related sustained virological response (SVR). SVR was defined as the last RNA test being negative at least 12 weeks after treatment completion.

FINDINGS:

• Receipt of curative antiviral treatment was associated with a reduction in the risk of cirrhosis, HCC, and overall mortality, irrespective of age.
• Elderly Veterans were significantly less likely to receive antiviral treatment; however, among those who received treatment, SVR was not different among the age groups (34% vs. 33% vs. 32%), even after adjusting for other demographic and clinical factors, including comorbidities.
• Older age was significantly associated with increased risk of developing cirrhosis and HCC. Veterans aged 65 to 85 years were 1.14 and 2.44 times more likely to develop cirrhosis and HCC than patients aged 20-49 years and 50-64 years, respectively. This association persisted after controlling for a range of factors, including diabetes and BMI.

IMPLICATIONS:

• Given the accelerated progression to advanced liver disease, elderly patients with chronic hepatitis C constitute a high-risk group that may need to be prioritized in the era of new antiviral treatments.

LIMITATIONS:

• This study is limited by the observational retrospective nature of its design.
• Study patients treated in the interferon era will likely have different comorbid disease burden than those treated in the direct-acting antiviral era, limiting the generalizability off the findings.
• Models did not control for factors that might preclude prescription for older antivirals (e.g., mental illness diagnoses and interferon).

AUTHOR/FUNDING INFORMATION:
This study was partly funded by HSR&D. All authors are part of HSR&D's Center for Innovations in Quality, Effectiveness and Safety (IQuESt) in Houston, TX.

El-Serag H, Kramer J, Duan Z, and Kanwal, F. Epidemiology and Outcomes of Hepatitis C Infection in Elderly U.S. Veterans. Journal of Viral Hepatitis. April 3, 2016; Epub ahead of print.