From the Journals

DAAs reduce mortality, cancer risk in HCV study

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Best evidence to date of reduced complications

This study provides “substantive evidence” that curing hepatitis C virus with all-oral direct-acting antiviral regimens provides clinical benefits, according to Raymond T. Chung, MD, and his coauthors of a related editorial.

Investigators in this study provide the best evidence so far in support of guidelines that advise direct-acting antiviral (DAA) treatment for all patients with chronic hepatitis C virus (HCV) infection, the editorial’s authors stated.

Results of the French study provide a strong counterpoint to the findings of a recent Cochrane review of DAA trials that could not confirm or reject whether DAAs had effects on long-term morbidity and mortality related to HCV, added Dr. Chung and his coauthors. “Finally, they provide credence to the achievability of the goals set out by the World Health Organization (WHO), not only to eliminate HCV but also to substantially reduce its complications.”

The WHO targets were established in light of earlier evidence that sustained virologic responses are linked to reductions in hepatocellular carcinoma, liver transplantation, and mortality, they said.

“In view of the high sustained virological response and excellent tolerability achieved with DAAs, it seemed highly plausible to envision reductions in chronic HCV infection–related complications with these drugs,” they said in reference to the study by Carrat and colleagues.

This editorial appearing in the Lancet was authored by Jacinta A. Holmes, Stephanie M. Rutledge, and Raymond T. Chung of the Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston. Dr. Chung provided disclosures related to AbbVie, Gilead, Merck, Bristol-Myers Squibb, Roche, Janssen, and Boehringer Ingelheim.



Direct-acting antivirals significantly decrease risk of hepatocellular carcinoma and mortality in persons with hepatitis C, according to results of the first prospective, longitudinal study to evaluate the effect of the drugs on complications related to the infection.

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Compared with no treatment, DAA therapy cut risk of hepatocellular carcinoma by about one-third and all-cause mortality by about half in the study, which included about 10,000 adult patients with chronic hepatitis C virus (HCV) infection treated at 1 of 32 hepatology centers in France (NCT01953458).

There were no signs of increased risk of hepatocellular carcinoma during treatment with DAAs, providing more evidence refuting earlier, single-center reports that had suggested an increased incidence early after treatment. These findings also counterbalance a recent Cochrane review that could not confirm or reject a potential benefit of drugs on long-term morbidity and mortality.

Results of the study, published in the Lancet, are based on analysis of 9,895 patients, including 7,344 who started DAA treatment and 2,551 who remained untreated at a median follow-up of more than 31 months. The median patient age was 56 years, and 53% were men.

Treatment with DAAs reduced risk of hepatocellular carcinoma when compared with no DAA treatment, with a hazard ratio of 0.66 (95% confidence interval, 0.46-0.93), and reduced risk of all-cause mortality, with an HR of 0.48 (95% CI, 0.33-0.70), investigators reported in a multivariable analysis that adjusted for variables including age, sex, fibrosis score, HCV genotype, alcohol use, and more.

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