News & Perspective

Direct-acting antivirals substantially cut the risk of liver cancer

2 years ago, OP Editor

Remarkable progress has been made in the development of successful antiviral therapies of hepatitis C virus (HCV) infection. However, it has been unclear whether HCV eradication by direct-acting antivirals (DAA) will also reduce the risk of hepatocellular carcinoma (HCC). At the Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD), encouraging data on DAA-induced sustained virological response (SVR) and the substantial reduction in HCC risk was presented.1

An unexpected finding was reported at the 2016 International Liver Congress (ILC), describing a high rate of hepatocellular carcinoma (HCC) recurrence in patients who achieved sustained virological response (SVR) to DAA.2 Indeed, the possibility that treatment with DAA may favor tumor growth and spread in individual patients with active HCC foci has been suggested, but remains unproven.3

“That was a very controversial finding because DAA eradicates hepatitis C with minimal side effects, and everything we know about hepatitis C and HCC tells us that if you eradicate hepatitis C, you should expect to reduce the risk of liver cancer, not increase it,” said the study author Dr. George Ioannou, associate professor at the University of Washington School of Medicine.4

“After that report, I think a lot of people were somewhat more cautious about antiviral treatment. So, it was very important to clarify that. And in some ways, our study deals with a more important and bigger issue – which is not recurrence, but does DAA prevent the development of liver cancer in the first place?” Dr. Ioannou further explained.4

The present findings are based on 62,051 patients who underwent 83,695 antiviral treatment regimens in the Veterans Affairs (VA) Puget Sound Healthcare System from 1999 to 2015.1,5 The data included 35,873 interferon‐only regimens, 26,178 DAA ± interferon regimens and 21,644 DAA‐only regimens.1,5

VA is the largest integrated health system providing hepatitis C care in the United States.6 Patients generally stay within the system, so it is possible to track those who receive antiviral treatment over the many years it takes to develop HCC, which cannot be assessed in randomized clinical trials.6

Most remarkably, the study showed that DAA-induced SVR was associated with an 79% reduction in HCC risk.1,5 SVR was associated with a significantly decreased risk of liver cancer in multivariable models regardless of whether the antiviral treatment was DAA‐only (adjusted hazard ratio [AHR] 0.29, 95% CI: 0.23‐0.37), DAA + interferon (AHR 0.48, 95% CI: 0.32‐0.73) or interferon‐only (AHR 0.32, 95% CI: 0.28‐0.37).1,5 “Receipt of DAA is not associated with increased HCC risk compared to receipt of interferon,” Dr. Ioannou concluded.6

“Eradicating hepatitis C will have a tremendous benefit in reducing liver cancer in individual patients and in the entire population,” said Dr. Ioannou. “Physicians and patients should not be withholding antiviral treatment for fear of inducing liver cancer. On the contrary, physicians should be treating hepatitis C specifically to reduce the risk of liver cancer.”5



  1. Ioannou GN, Green P, Berry K. Eradication of HCV induced by direct-acting antivirals is associated with a 71% reduction in HCC risk. The Liver Meeting 2017. October 20-24, 2017; Washington, DC. Abstract 142.
  2. Buonfiglioli F, Conti F, Andreone A, et al. Development of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. EASL International Liver Congress 2016. April 13-17, 2016; Barcelona. Abstract LBP506.
  3. Alberti A, Piovesan S. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: Fact or fiction? Liver Int. 2017;37(6):802-808.
  4. Direct-acting Antivirals Cut Risk of Liver Cancer. Medscape. 2017 (Accessed December 5, 2017, at
  5. Direct‐Acting Antiviral Therapy Cuts Liver Cancer Risk By 71%. AASLD Press Room. 2017 (Accessed December 6, 2017, at
  6. AASLD 2017: Curing Hepatitis C with DAAs Reduces Liver Cancer Risk. 2017 (Accessed December 6, 2017, at


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