Editorial

HCC After DAAs Requires More Study, but no Cause for Withheld Treatment

As we continue to see the success of direct-acting antiviral therapy in treating hepatitis C virus, we must be aware of any potential complications from the underlying liver disease after successful treatment, especially hepatocellular carcinoma.

In the pre-DAA era, studies showed a reduction of HCC occurrence in patients with HCV who attained SVR. In a 2012 study by Adriaan J. van der Meer, MD, and colleagues, the 10-year cumulative occurrence rate of HCC was just 5.1% in patients who met SVR, in contrast to 21.8% in those who failed interferon-based therapies. A pooled analysis by Rebecca L. Morgan, MPH, and colleagues, in 2013 showed a significant reduction in HCC post-SVR: 1.5% of SVR patients developed HCC vs. 6.2% of non-SVR. Yet, at both the International Liver Congress in 2016 and subsequently, studies have led us, rather unexpectedly, to question whether DAA therapy may affect a patient adversely with regard to the development of HCC both in patients with a history of HCC and in a de novo fashion.

ILC 2016 Data

In a Late Breaking presentation in Barcelona, we saw data on 344 patients with HCV-related Child-Pugh A/B cirrhosis, without active HCC. They were treated with a variety of DAAs, with or without ribavirin, and occurrence of HCC was monitored through 6 months.

At the end of the follow-up period, 7.6% of all patients were diagnosed with HCC with 29% (17/59) of those with previous treated HCC showing recurrence. In contrast, only 3.2% (9/285) of those without such a history presented with de novo HCC.

In a similar vein, a study by María Reig, MD, and her Barcelona colleagues looked at 58 patients with a history of HCC followed by treatment with DAAs. They showed that 16 patients (27.6%) had radiologic recurrence within a median 5.7 months of follow-up. In a commentary on Reig’s study, Ju Dong Yang, MD, and colleagues showed that patients on the waiting list for liver transplant for HCV-associated HCC who received pre-transplant DAA therapy trended toward a higher HCC recurrence (27.8%) vs. their untreated counterparts (9.5%). The authors of this study did mention that three of the five patients who recurred in the treated group had not achieved SVR.

In decompensated cirrhotics, Michelle Cheung, MD, MPH, FAAP, showed no signal for increased rates of HCC after DAA-induced SVR. The researchers followed more than 406 patients up to 15 months and saw a 4% occurrence of HCC in the first 6 months, whether treated or untreated. In those who achieved SVR24, there was a 5.4% rate of HCC as compared to 4.2% in the untreated arm. In those that failed DAA therapy, the rate of HCC was 11.2%.