Direct-acting antiviral agents significantly lower Hepatitis C related mortality and cancer risk

1. In this retrospective cohort study, adult patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents had significantly lower mortality and a 27% lower risk of developing hepatocellular carcinoma (HCC) than patients with untreated HCV infection.

2. Patients who received DAA treatment for HCV had a lower risk of developing diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) than patients with untreated HCV.

Evidence Rating Level: 2 (Good)

Untreated chronic hepatitis C (CHC) commonly progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In addition to these hepatic complications, CHC may cause extrahepatic manifestations that increase morbidity and mortality. Previous research surrounding interferon-based treatment has revealed that it reduces overall mortality, liver-related complications, and non-liver-related complications. However, interferon-based treatment lacks efficacy and is poorly tolerated, especially in older adults. In recent times, there have been major improvements in hepatitis C virus (HCV) therapies, specifically direct-acting antiviral (DAA) agents. A short course of all-oral DAA treatment can achieve virologic cure in almost all treated patients, but the effects of DAAs on other non-liver comorbidities have not yet been studied. This was a large retrospective cohort study of adults with HCV infection, drawing data from a large deidentified administrative health claims database. Included were patients with HCV infection from January 2010 to March 2021, and baseline characteristics were collected prior to the diagnosis of HCV infection. The primary endpoints were the incidence of liver-related outcomes and mortality, while the secondary endpoints included the incidence of non-liver outcomes. 245,596 patients with HCV infection met the inclusion criteria and were included in the analysis. 40654 (16.6%) patients had received at least 1 prescription for DAA medication, and 204942 (83.4%) had not. With respect to baseline characteristics, DAA-patients were more likely than untreated patients to be male (P<.001) and to have compensated cirrhosis (P<.001) or diabetes (P<.001). Regarding the primary endpoints, the mortality rate per 1000 person-years was twice as high in untreated patients compared with DAA-treated patients (64.7 vs 36.5, P<.001). Furthermore, DAA treatment was associated with a 27% lower risk of developing HCC (adjusted HRs [aHRs], 0.73; 95% CI, 0.68-0.77; P<.001) and a 64% reduction in the risk of developing liver decompensation (aHR, 0.36; 95% CI, 0.35-0.38; P<.001). In addition, DAA treatment was associated with a lower risk of developing diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Overall, this large retrospective cohort study found that patients with DAA-treated HCV had significantly lower mortality and incidence of liver and non-liver complications that patients with untreated HCV. A major limitation of this study is the inclusion of patients only covered with private insurance, which may not be generalizable to the overall population. This study adds to the growing body of evidence support DAA use for treatment of Hepatitis C.

Click to read the study in JAMA Internal Medicine

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