HCV drugs may hasten liver cancer recurrence

Researchers have unexpectedly found early tumor recurrence in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma in patients undergoing interferon-free therapy, according to a new study.

“The success of direct-acting antivirals (DAAs) against hepatitis C is a major breakthrough. Until now, however, there are very few data on the effect of HCV eradication in patients who have already developed hepatocellular carcinoma,” the researchers, led by senior author Jordi Bruix of the Barcelona Clinic Liver Cancer Group at the University of Barcelona, said in a statement.

They found a “high rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.” The study was published online April 13, 2016, in the Journal of Hepatology and simultaneously presented at The International Liver Congress in Barcelona, Spain.

The Spanish researchers conducted a study of 58 patients with HCV infection and prior history of treated hepatocellular carcinoma who achieved complete response. The patients lacked non-characterized nodules at the time they underwent anti-HCV treatment with all-oral DAAs in four hospitals. Patients receiving interferon as part of the antiviral regimen were excluded from the study.

The baseline characteristics, laboratory and radiologic tumor response were registered in all patients before starting antiviral therapy and during the follow-up.

After a median follow-up of 5.7 months, three patients died and 16 patients developed radiologic tumor recurrence (27.6%). The pattern of recurrence included intrahepatic growth in three patients, new intrahepatic lesion (one nodule in 5 patients, up to three nodules less or equal to 3 cm in four patients,  and multifocal in one patient) and infiltrative ill-defined hepatocellular carcinoma and/or extra-hepatic lesions in three patients.

The researchers concluded that “our data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, though based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity.”

Raymond Chung, MD, vice chief of the gastrointestinal unit and medical director for the liver transplant program at Massachusetts General Hospital, told Medical Economics, “HCV is an important risk factor for liver cancer. Those with a history of liver cancer remain at increased risk for recurrence, and this risk does not go away with successful clearance of HCV. This is likely because of the structural changes of cirrhosis that remain, along with the chronic DNA damage and mutations that give rise to cancer that developed during chronic infection. In short, we must maintain vigilance for the development of cancer even after viral cure in persons who were at risk for cancer, such as those who have advanced fibrosis or cirrhosis.”

Chung added that “further study is required in considerably larger numbers of patients before any conclusion can be drawn regarding an increased risk for recurrent hepatocellular cancer following viral clearance with DAAs.”

He noted that “cure of HCV is associated with overwhelming benefits, including reduction of liver-disease related mortality.”