Direct-Acting Antivirals Reduce Mortality, Hepatocellular Carcinoma in HCV

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Researchers postulated that patients with chronic HCV who were never treated with direct antivirals had a higher incidence of HCC.

In patients with chronic hepatitis C virus (HCV) infection, treatment with direct-acting antivirals (DAAs) is associated with reduced risks for mortality and hepatocellular carcinoma, according to study results published in The Lancet. The researchers recommend that DAA treatment be considered in all patients with chronic HCV infection.

The study included adults with chronic HCV infection from 32 expert hepatology centers in France (n=9895). The researchers excluded participants with chronic hepatitis B, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, or treatment with interferon-ribavirin with or without first-generation protease inhibitors. The primary outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis.

The median follow-up time was 33.4 months, during which 7344 participants initiated treatment with DAAs, while 2551 remained untreated. During follow-up, 218 participants died (129 treated, 89 untreated), 258 were diagnosed with hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated).

Before adjusting for variables, the results indicated that treatment with DAAs was associated with an increased risk for hepatocellular carcinoma (hazard ratio [HR], 2.77; 95%; CI, 2.07-3.71) and decompensated cirrhosis (HR, 3.83; 95% CI, 2.29-6.42).

However, after adjusting for variables (age, sex, body mass index, geographic origin, infection route, fibrosis score, being HCV treatment-naïve, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biologic variables, and model for end-stage liver disease score in participants with cirrhosis), the researchers found that treatment with DAAs was associated with a decrease in all-cause mortality (HR, 0.48; 95% CI, 0.33-0.70) and hepatocellular carcinoma (HR, 0.66; 95% CI, 0.46-0.93). DAAs were not associated with decompensated cirrhosis (HR, 1.14; 95% CI, 0.57-2.27).

“To our knowledge, the ANRS CO22 Hepather cohort study is the first prospective longitudinal study to investigate clinical outcomes associated with direct-acting antiviral treatment in patients with chronic HCV infection, by comparing patients treated with direct-acting antivirals with those untreated with these drugs, irrespective of the status of sustained virological response, with careful control of confounding and indication biases,” the researchers wrote.

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Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study [published online February 11, 2019]. The Lancet. doi:10.1016/S0140-6736(18)32111-1