Direct-acting-antivirals (DAA) can cure patients of the life-threating hepatitis C virus (HCV) infection, with cure rates exceeding 95%. However, questions have been raised about the long-term consequences of curing patients with DAAs, including a potential link between DAA treatment and the development of hepatocellular carcinoma (HCC).
A variety of research studies have been presented during the Liver Meeting of the European Association for the Study of the Liver (EASL) held in Amsterdam, and the collective data indicate that patients without previous HCC incidence are not at a significantly increased risk of developing HCC, although patients who have previously been cured of HCC might be at elevated risk of recurrence and might experience a more aggressive HCC after being cured of HCV.
Researchers have hypothesized that the elimination of HCV might promote the development of HCC or accelerate the growth of HCC tumors. This hypothesis is based on the idea that the inflammation caused by the chronic HCV infection can prevent the outbreak and/or growth or carcinogenic cells in the liver.
In fact, a study presented during the liver meeting indicated that the cirrhotic HCV patients without diagnosed HCC have elevated T-cell activity against HCC markers and that the activity diminishes after HCV elimination. However, the HCV itself also increases patient’s risk of developing HCC, implying a possible reduction in HCC risk after HCV elimination—but the interplay between these different mechanisms is not well understood.
Multiple studies presented during the EASL Liver Meeting now substantiate the claim that DAA treatment itself might not increase the long-term risk of HCC, although the risk might be time-dependent. For example, the risk of developing HCC appears to be slightly elevated during the months immediately following cure. However, it is not yet clear if this represents an increased risk of developing de novo HCC, or of accelerated growth due to undiagnosed HCC presents as small nodules prior to HCV cure. Due to the recent approval of DAAs, no long-term data are available.
The situation differs, however, for patients who had been cured of HCC prior to DAA treatment. The risk of recurrence is generally high for these individuals, and the presented data indicate that this risk might be further elevated after HCV elimination. Furthermore, the growth of these tumors appears to be slightly elevated, indicating a more aggressive cancer compared with patients who were not treated with DAAs.
The strongest correlation between DAA treatment and HCC was observed for patients who were treated with DAAs but did not achieve cure of HCV. The reason for this correlation is not yet known.
Collectively, these preliminary data suggest that for patients without previous HCC the risk/benefit ratio far outweighs in favor of DAA treatment although close observation of HCC is warranted, in particular during the first months following cure. Although the circumstances are slightly different for patients with previous HCC, it is not yet clear if DAA treatment reduces life expectancy.