Editorial: can experimental biomarkers be useful for predicting HCC occurrence after sustained viral response in clinical settings?

Direct-acting antivirals (DAAs) for patients with chronic hepatitis C (CHC) reduce - but do not completely eliminate - the incidence of hepatocellular carcinoma (HCC).1 It is important to stratify the risk of HCC after achieving a sustained viral response (SVR). Some clinical indicators, including age, platelet count, cirrhosis, and alpha-fetoprotein (AFP) level have been useful for predicting HCC occurrence after SVR.2 However, more reliable markers are needed to reduce the medical cost and patient burden of HCC screening after SVR.

Myojin et al have explored the longitudinal changes in serum growth differentiation factor 15 (GDF15) in patients with CHC before and after DAA treatment.3 Pre-treatment elevated GDF15 levels predicted HCC occurrence after SVR in the exploratory measure. Furthermore, in the risk scoring segment, they created a scoring system for predicting HCC using GDF15, AFP, and Fib-4 index in the derivation cohort (n = 964). The cut-off values of GDF15, AFP, and Fib-4 were 1350 pg/ml, 5 ng/ml, and 3.25, respectively. The cumulative HCC occurrence rates were higher in the high-score group (score = 3) than in the low- (score = 0) and middle-score (score = 1-2) groups. Similar findings were observed in the validation cohort (n = 642). Because the predictive capabilities of GDF15 and the scoring system did not decrease in the validation cohort, these results seem to be robust.

GDF15, which is secreted by activated hepatic stellate cells, is a cytokine belonging to the transforming growth factor-β superfamily.4 The expression of GDF15 increases in response to oxidative and mitochondrial stress.5-7 Therefore, this study suggests that oxidative and mitochondrial stress may have an impact on HCC occurrence after SVR. No patients with low GDF15 developed HCC after 3 years from baseline in either the derivation or validation cohorts. If these findings are confirmed elsewhere, and patients with low GDF15 do not develop HCC after a longer follow-up, the intensity of HCC screening for these patients could be decreased.

Recently, some experimental biomarkers, including molecular-targeting markers and single nucleotide polymorphisms, have been reported to predict HCC occurrence after SVR.2 However, it is difficult to apply these experimental biomarkers to clinical settings because of cost, measurement procedures, and sample collection. In this study, GDF15 levels were measured in serum samples using an enzyme-linked immunosorbent assay kit and thus can be easily measured in clinical settings.

DAA treatment produces SVR in the vast majority of patients with CHC. Post-SVR HCC occurrence remains a hazard. This study indicates that elevated pre-treatment GDF15 levels predict HCC occurrence after SVR. The utility of GDF15 in different settings and the potential of its therapeutic targeting should be further evaluated in the future.

We would like to thank Editage (www.editage.com) for English language editing.

Declaration of personal interests: None.

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