Use of direct-acting antiviral (DAA) medications for hepatitis C virus (HCV) infection was associated with a 71% reduced risk of hepatocellular carcinoma (HCC) in a study of more than 62,000 patients with HCV, according to results presented October 21 at The Liver Meeting® held by the American Association for the Study of Liver Diseases in Washington, DC.
Still relatively new, DAA therapy has several advantages over interferon for treating chronic HCV infection, such as high sustained viral response (SVR) and less toxicity. But recent investigations have reported an unexpectedly high rate of HCC recurrence after DAA treatment.
The researchers of this study wanted to determine whether DAA treatment is associated with a reduced risk of HCC in patients with HCV. They also sought to compare HCV risk reduction between DAA treatment and interferon-based therapy.
“It is tempting to assume that if we eradicate hepatitis C, the risk of liver cancer will also be eradicated or at least substantially reduced,” said lead investigator George N. Ioannou, MD, MS, associate professor of gastroenterology at the University of Washington School of Medicine, Seattle, WA.
But, patients with HCV may develop cirrhosis or advanced fibrosis while infected, putting them at risk of HCC even after the virus is eradicated, he explained.
“Furthermore, recent studies suggested an increased risk of liver cancer in patients with HCV who were treated with the new DAAs,” Dr. Ioannou added. “This made it all the more imperative for us to determine whether DAA-induced eradication of HCV is associated with a reduction in liver cancer risk using an adequately powered study.”
Reducing HCC risk
Dr. Ioannou and colleagues used data from the Veterans Affairs Puget Sound Healthcare System to identify 62,051 patients with HCV who underwent a total of 83,695 antiviral treatment regimens from 1999 to 2015. Of the treatment regimens, 35,873 were interferon only, 26,178 were DAA plus interferon, and 21,644 were DAA only. The researchers adjusted for a large number of potential confounders and used Cox proportional hazards regression to determine the association between SVR and HCC risk.
They identified 3,271 incident cases of HCC diagnosed at least 180 days after the start of antiviral treatment during an average follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24).
Sustained viral response was associated with a significant reduction in HCC risk regardless of whether the antiviral treatment was DAA only (adjusted hazard ratio [AHR] 0.29, 95% CI: 0.23-0.37), DAA plus interferon (AHR 0.48, 95% CI: 0.32-0.73), or interferon only (AHR 0.32, 95% CI: 0.28-0.37).
Notably, patients who received DAA only or DAA plus interferon had no greater risk of HCC compared with those given interferon only.
“Physicians and patients should not be withholding antiviral treatment for fear of inducing liver cancer,” Dr. Ioannou said. “On the contrary, physicians should be treating hepatitis C specifically to reduce the risk of liver cancer.”
This study was funded by a NIH/NCI grant and VA CSR&D grant. Janssen Pharmaceuticals also provided Dr. Ioannou with grant/research support.