Large study finds increased risk of hepatocellular carcinoma with cirrhosis, but not with direct-acting antiviral HCV treatment.
Fasiha Kanwal, MD
Results from a large cohort study alleviate concerns that direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) could increase risk of heptatocellular carcinoma (HCC), while confirming that cirrhosis is a prominent factor in HCC — the fastest growing cause of cancer-related deaths in the US.
There had been no consensus on the possibility that DAA treatment could increase risk for HCC as recently as the 2017 International Liver Congress, due to the inconsistent findings from relatively small trials, Raoel Maan, MD — Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam — and Jordan Feld, MD, MPH — Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto — noted in commentary accompanying the study.
"The studies were generally small and of varying quality, leaving clinicians uncertain of how to advise their patients,” researchers wrote. “In short, the HCV community needed larger cohort studies.”
They credited the researchers of the new large cohort study, however, for having answered that need, and having likely “closed the case on the HCC occurrence issue after achieving sustained virologic response (SVR)."
Fasiha Kanwal, MD — Professor of Medicine and Interim Chief, Gastroenterology, Baylor College of Medicine — and colleagues conducted a retrospective cohort study of 22,500 patients in Veterans Health Administration hospitals who received DAA treatment in 2015 for HCV infection, including 39% with cirrhosis.
In addition to analyzing risk from incidence rates, they also considered the aggressiveness of newly emergent HCC during and after DAA treatment, from presence of multifocal and advanced tumors.
In the follow-up through September 2016, there were 271 new cases of HCC, including in 183 patients who had achieved SVR. Patients achieving SVR with the DAA treatment had a significantly reduced incidence of HCC (0.9%, 95% Confidence Interval [CI] 0.77-1.03) than those who did not (3.45%, CI 2.73-4.18).
After controlling for baseline factors, SVR was associated with reduced risk with adjusted hazard ratio of 0.28. Although there was a higher incidence of HCC in those with cirrhosis, attaining SVR with the DAA treatment showed a similar protective effect, with adjusted hazard ratio of 0.32. There was no difference in tumor size or stage in HCC emerging during or after DAA treatment.
Kanwal and colleagues noted that the HCC preventative effect of SVR was evident early in treatment, and increased over time.
"These data show that successful eradication of HCV confers a benefit in patients treated with DAA,” researchers wrote. “Although few recent studies have raised concerns that DAA might accelerate the risk of HCC in some patients early in the course of treatment, we did not find any factors that differentiated patients with HCC that developed during DAA treatment compared with HCC that developed later in follow-up."
The collective findings did not support the notion that DAAs promote hepatocarcinogensis, researchers concluded.
Maan and Feld concurred with that conclusion, adding that since achieving SVR does not eliminate risk of the development of HCC in those with cirrhosis, "early treatment to prevent cirrhosis is the preferred strategy.”
The large cohort study of risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents was published in the October issue of Gastroenterology.