The Impact of HCV Eradication by Direct-acting Antivirals on the Transition of Precancerous Hepatic Nodules to HCC

A Prospective Observational Study

Hidenori Toyoda; Takashi Kumada; Toshifumi Tada; Kazuyuki Mizuno; Yasuhiro Sone; Tomoyuki Akita; Junko Tanaka; Philip J. Johnson


Liver International. 2019;39(3):448-454. 

In This Article


In the present study, patients with NHHNs at baseline were prospectively observed for up to 2 years and during this period, the incidences of hypervascularization of these nodules, that is transition to typical HCC, were similar between patients with HCV eradication and those with persistent HCV infection. Also, when considering only patients without NHHNs at baseline, both groups showed a similar incidence of the emergence of these nodules. Thus, the likelihood of developing HCC did not change during the 2-year observation period after the eradication of HCV. We found no evidence that SVR either suppressed or promoted HCC development.

Another important finding was that no patient experienced the direct emergence of hypervascular HCC after SVR whereas some patients with baseline NHHNs showed transition to hypervascular HCC. This suggests that, in most cases, typical hypervascular HCC develops as the hypervascularization of NHHNs, and rapid emergence of hypervascular HCC would not occur after SVR.

Although considerable controversy surrounds the topic, evidence both in support of, and against, the preventive effect of SVR on HCC development has, until now, relied on analysis of retrospective data. The main strength of our current paper is that it prospectively tests the hypothesis that HCV eradication influences HCC development and found no evidence in support of such a hypothesis.

There are, however, also limitations to this study. The period of observation was short. The age of patients with chronic hepatitis C who are candidates for anti-HCV therapy with DAAs is higher in Japan than in Western countries, and the influence of HCV eradication on HCC development may differ among regions. Another limitation is that the study population did not include patients with decompensated cirrhosis, for whom DAA therapy is not allowed in Japan. In addition, the control patients, who had persistent HCV infection, were not randomized with the patients who achieved SVR but with the current availability of effective (DAA) antiviral therapy such randomization would be neither practical nor ethical. Nonetheless, the two groups' backgrounds were balanced using propensity score matching. Although NHHNs at baseline might have been a mixture of precancerous dysplastic nodules and non-hypervascular very early stage HCC in both groups, the mixture could also be balanced by propensity score matching. Finally, the present study focused on patients without a history of HCC. Therefore, the effects of HCV eradication on the recurrence of HCC in patients who had completed HCC treatment may differ from those demonstrated in this study and should be investigated further. In particular, there are two distinct patterns in cases of the recurrence of HCC after SVR: hypervascularization of NHHNs at baseline and the direct emergence of hypervascular typical HCC without baseline NHHNs. These two patterns may reflect multicentric recurrence and intrahepatic metastasis.[25] The effect of HCV eradication on the recurrences of HCC should be analysed being categorized based on the pattern of recurrences.

In conclusion, among patients without a history of HCC, we found no evidence that eradication of HCV by DAA therapy influenced HCC development (as shown by hypervascularization of NHHNs) or the new emergence of NHHNs.