Hepatitis C Antivirals Not Linked to Elevated Liver Cancer Recurrence

An assessment of over 62,000 patients treated for hepatitis C (HCV) revealed no evidence to support the suggestion that direct acting antiviral (DAA) agents promote recurrence of hepatocellular carcinoma (HCC), and found instead that successful treatment with or without DAAs is associated with reduced risk of HCC.

Despite the success of DAA-based treatments in producing virtual cures of HCV marked by sustained virologic response (SVR), several recent studies have found little or no impact of the treatments on HCC risk, and some have posed the possibility that they might increase risk.

Most recently, in a May 2017 report in Seminars In Liver Disease, Maria Reig, MD, PhD, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, and colleagues updated and extrapolated from their earlier cohort study, indicating that "not all data (on DAA-based treatments) are positive."

"In April 2016, we published a cohort study suggesting that viral eradication with the new agents could be associated in time with the emergence of recurrent cancer sites in patients previously treated for hepatocellular carcinoma," researchers wrote.

In a retrospective study of 62,354 patients with HCV treated in the VA system, however, George Ioannou, MD (pictured), Division of Gastroenterology, Department of Medicine VA Puget Sound Health Care System and University of Washington, Seattle, and colleagues found no such risk associated with any successful treatment — whether or not DAA-based. They attributed the putative association to inadequate assessment of the question.

"These studies were grossly underpowered, had very limited follow-up time, studied mostly HCC recurrence rather than incidence, and did not attempt to compare those who achieved SVR as a result of DAAs to those who did not with respect to HCC risk," researchers

Of the patients who were treated for HCV at the VA in the period between 1999 and 2015, 58% (35,871) received an interferon-only regimen, 7.2% (4,535) DAA plus interferon, and 35% (21,948) DAA-only regimen. Ioannou followed the course of these patients retrospectively through June 15, 2017 to identify incident cases of HCC.

The investigators identified 3,271 incident cases diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up period of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years). Those with cirrhosis and SVR had an incidence of 1.97 per 100 patient-years, followed by patients with no cirrhosis and treatment failure (0.87), and the least frequent occurrence (0.24) in those without cirrhosis who achieved SVR.

SVR was associated with significantly decreased risk of HCC irrespective of whether the treatment was DAA-only, DAA plus interferon, or interferon-only.

"DAA-induced SVR is associated with a 71% reduction in HCC risk compared to treatment failure,” researchers concluded. “Eradication of HCV is associated with a similar reduction in HCC risk irrespective of the regimen that is used to achieve eradication. We found no evidence that treatment with DAAs was associated with increased risk of HCC compared to treatment with interferon.”

The study, "HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma," was published online in the Journal of Hepatology last month.