Higher Levels of Fibrosis in a Cohort of Veterans with Chronic Viral Hepatitis are Associated with Extrahepatic Cancers

Abstract

Background and aims: An estimated 2.4 million Americans, including more than 150,000 veterans, are chronically infected with hepatitis C virus (HCV). HCV is estimated to cause roughly 25% of all hepatocellular carcinoma. Although its mechanism is unknown, developing evidence suggests that chronic HCV infection is also associated with the development of extrahepatic cancers (EHCs). This paper aims to assess the relationship of hepatic fibrosis and chronic HCV with the risk of developing EHC.

Methods: We conducted a single-center retrospective chart review of 1541 patients linked to the hepatitis clinic at the Veterans Affairs (VA) Maryland Health Care System who underwent transient elastography for evaluation and management of liver disease from 2014 to 2018. Liver fibrosis was measured using ultrasound and transient elastography. Extrahepatic cancer and site was identified by a retrospective chart review.

Results: In adjusted analysis of EHCs, advanced age (OR: 1.97, 95% CI: 1.30-3.04), and higher measured stiffness (OR 2.19, 95% CI: 1.32-3.64) were associated with an increased likelihood of developing EHC, controlling for HBV infection, HCV exposure, heavy alcohol use, and body mass index.

Conclusions: We observed a significant association between increasing age and increasing levels of liver fibrosis with increased risk of EHC, notably prostate, head and neck squamous cell, lung, and hematologic cancers.

Keywords: CAP, Controlled attenuation parameter; DAA therapy; EHC, Extrahepatic cancer; HBV, Hepatitis B Virus; HCC, Hepatocellular carcinoma; HCV, Hepatitis C Virus; HIV, Human Immunodeficiency Virus; NASH, Nonalcoholic steatohepatitis; VA, Veterans Affairs; VAMHCS, Veterans Affairs Maryland Health Care System; extrahepatic cancer; hepatitis B virus; hepatitis C virus; liver fibrosis.