The U.S. Preventive Services Task Force (USPSTF) recently expanded its recommendation on screening for hepatitis C virus (HCV) to include all adults ages 18 to 79 years (B recommendation). The recommendation is an update of the 2013 USPSTF recommendation for screening in patients at high risk for infection as well as one-time screening for adults born between 1945 and 1965.
The new recommendation statement was published online on March 2 by JAMA and was summarized in the March 27 ACP Gastroenterology Monthly. The following commentary, by Ronald L. Koretz, MD, FACP, appeared in the ACP Journal Club section of the July 21 Annals of Internal Medicine.
An essential requirement for instituting screening is the availability of effective treatment. For patients with chronic HCV infections, <20% will develop end-stage liver disease (ESLD), namely decompensated cirrhosis or hepatocellular carcinoma, so most infected patients do not need any intervention. Currently, no randomized controlled trials (RCTs) show that treatment improves mortality or morbidity. A Cochrane review of 138 RCTs reported no short-term (<1 y) benefits of direct-acting antiviral (DAA) therapy versus no treatment on clinical outcomes; long-term data were not available. Although DAAs result in sustained virologic response (SVR), this is an unvalidated surrogate outcome. In the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial, the peginterferon group showed an increase in SVR but also increased mortality, compared with a control group not receiving peginterferon.
SVR is not always a cure; patients achieving it can still develop ESLD and have hepatitis C viral RNA in other tissues. Although treated patients who achieve SVR have better outcomes than those who do not (as reported by Owens and colleagues), these benefits cannot be attributed to the treatment because all patients were treated. Because of well-publicized marketing of optimistic expectations for DAA treatments, effects on quality of life need to be assessed in double-blind (including blinding of laboratory tests) RCTs; no such trials are yet available. Published models have used overly optimistic and incorrect assumptions. Given the weakness of the evidence base supporting DAA treatment, any recommendation to screen and identify patients for treatment with expensive medications is premature. Given remaining equipoise, it would be ethical to perform RCTs of treatment versus no treatment to assess the effect of DAAs on clinical outcomes. Using the HALT-C study design as a model, such trials could be accomplished in a few years.