Patients with hepatitis C virus (HCV) who are being treated with direct-acting antiviral treatments (DAAs) and who have been successfully treated for hepatocellular carcinoma (HCC) have a high rate of HCC recurrence, according to a retrospective cohort study.1

The National Cancer Institute estimated that there will be 39,230 new cases of liver cancer in the United States in 2016, accounting for 2.3% of all new cancer cases, and 27,170 deaths, accounting for 4.6% of all cancer-related deaths.2 Only 17.5% of patients with liver cancer survive 5 years after diagnosis.2

“This is probably not a direct effect of the antiviral therapy,” said study coauthor Stefano Brillanti, MD, of the University of Bologna in Italy, in an interview with Cancer Therapy Advisor. “A possible explanation is related to a downregulation of the immune surveillance, because of the abrupt reduction in the inflammatory infiltrate in the liver after disappearance of HCV.”

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Dr Brillanti also explained that the data did not indicate that patients treated with DAAs for HCV have an elevated risk of developing novel HCC.

“The risk seems limited to recurrence of liver cancer in those who experienced neoplastic transformation of the liver in the past,” said Dr Brillanti. “These patients are at high risk of recurrence even if they are not treated with antivirals. Antivirals may anticipate the recurrence in a way we are still not aware of.”

The researchers enrolled 344 patients with HCV-related cirrhosis who did not have active HCC; however, 59 had a history of previous HCC. All patients were treated with the DAAs sofosbuvir plus simeprevir (34% of patients), 3D combination (ABT-450 plus ritonavir, ombitasvir, dasabuvir, and ribavirin; 22%), sofosbuvir plus ribavirin (17%), sofosbuvir plus daclatasvir (16%), or sofosbuvir plus ledipasvir (10%).

At 12 weeks post-treatment, 89% of patients attained sustained virologic response. Active HCC was detected in 7.6% of patients at 24 weeks post-treatment, which the authors described as a “standard rate of occurrence.” Among those who had a previous history of HCC, 29% developed a recurrence of the disease, which the authors considered a “high rate of recurrence.”

The authors recommended “close monitoring” for patients with HCC following treatment and said that further investigations into the biological significance of their findings are warranted.

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“Close monitoring means abdominal ultrasound and alpha-fetoprotein performed every 6 months for at least 5 years after antiviral treatment,” said Dr Brillanti. “Recurrent HCC should be treated as usual, according to liver disease stage and cancer diffusion.”

Dr Brillanti also urged hepatologists to counsel their patients on the risks associated with DAA treatment.

“Cirrhotic patients with a history of previously treated HCC should be advised of the potential risk of recurrence after antiviral therapy,” he said. “On the other hand, not treating these patients with antivirals will lead to progression of cirrhosis toward decompensated liver disease.”


  1. Buonfiglioni F, Conti F, Andreone P, et al. Development of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. Poster presented at: The International Liver Congress 2016, EASL; April 13-17, 2016: Barcelona, Spain.
  2. National Cancer Institute. SEER Stat Fact Sheets: Liver and Intrahepatic Bile Duct Cancer. Accessed May 27, 2016.