Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study

Abstract

BACKGROUND: The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. METHODS: We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. RESULTS: Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). CONCLUSIONS: Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.