Large Study Supports Direct-Acting Antiviral Link to Reduced Mortality, Liver Cancer Risk in HCV

New research supports the use of direct-acting antiviral therapy for all individuals with chronic hepatitis C infection.

New research has confirmed the long-term efficacy of direct-acting antivirals (DAAs) in reducing the risk for mortality and liver cancer among patients with chronic hepatitis C virus (HCV) infection, according to a recent study published in The Lancet.

It is known that HCV causes complications such as cirrhosis, liver disease, hepatocellular carcinoma, and can result in death. Currently, an estimated 71 million individuals are chronically infected with HCV.

Although DAAs are commonly used to treat chronic HCV infection, there is little reported evidence supporting their clinical benefit. Previous research has indicated a reduced risk of complications in patients treated with DAAs, but few studies have compared both treated and untreated patients. A recent Cochrane Review found no evidence for or against the treatment having a long-term effect on mortality and disease. This study is the first prospective, longitudinal study investigating the treatment of chronic HCV with DAAs and its association with mortality and liver cancer risk.

For the study, 10,166 adult patients with chronic HCV infection from 32 centers in France were analyzed. Patients with a history of chronic hepatitis B, decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation were excluded, as well as patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Ninety-seven percent of patients had available follow-up information.

In the study, treatment with DAAs was initiated during follow up in 7344 patients and 2551 patients remained untreated. According to the findings, 218 patients died, 258 reported hepatocellular carcinoma, and 106 had decompensated cirrhosis. DAAs were associated with reduced risk for global mortality and hepatocellular cancer, but not decompensation of cirrhosis. Patients treated with DAAs were 52% less likely to die prematurely than those who were untreated and 33% less likely to develop hepatocellular carcinoma.

In 3045 patients with cirrhosis at baseline, the same association was observed for mortality and hepatocellular carcinoma.

According to the study authors, the positive data showing the long-term outcomes of patients who received DAA therapy in the large cohort support the use of this treatment in all patients with chronic HCV infection.

“The study by Carrat and colleagues offers substantive evidence that cure of HCV delivered by all-oral direct-acting antiviral regimens is associated with clinical benefits.” Raymond T Chung, MD, director of the Liver Center at Massachusetts General Hospital, wrote in a commentary. “These findings firmly counter those of a Cochrane review of direct-acting antiviral treatment trials that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality.”


Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatments: a prospective cohort study. The Lancet. February 11, 2019.

Holmes JA, Rutledge SM, Chung RT, et al. Direct-acting antiviral treatment for hepatitis C. The Lancet. February 11, 2019.