Circulating Let-7 Family Members as Non-Invasive Biomarkers for Predicting Hepatocellular Carcinoma Risk after Antiviral Treatment among Chronic Hepatitis C Patients

SIMPLE SUMMARY: Cost-effective, Hepatocellular carcinoma (HCC) risk-based surveillance strategies should be established after achieving sustained virologic response (SVR). Circulating microRNAs are considered stable serum markers for early cancer diagnosis and prognosis and treatment response prediction. The aim of our longitudinal follow-up study was to assess whether Let-7 family members can predict HCC risk in CHC patients. We assessed the sera of 54 patients with CHC who developed HCC and 173 patients with CHC who did not develop HCC after antiviral therapy. Cox’s regression model revealed the independent role of let-7i as an effective surrogate biomarker for predicting HCC development in patients with CHC. ABSTRACT: HCC, a leading cause of cancer-related mortality, is diagnosed at advanced stages. Although antiviral therapy has reduced the risk of HCC among chronic hepatitis C (CHC) patients, the risk of HCC remains, thus, highlighting the unmet need for continuous surveillance. Therefore, stable and cost-effective biomarkers, such as circulating microRNAs, must be identified. We aimed to clarify whether serum levels of the Let-7 family can predict HCC risk in patients with CHC using univariate and multivariate Cox’s proportional hazards model. We analyzed the sera of 54 patients with CHC who developed HCC after antiviral therapy and compared the data with those of 173 patients without HCC development. The Let-7 family (except for let-7c) exhibited significant negative correlations with the fibrosis score (r = −0.2736 to −0.34, p = 0.0002 to <0.0001). After Cox’s regression model was used to adjust for age, sex, HCV genotype, and FIB-4 ≥ 3.25, patients with CHC with let-7i median ≥ −1.696 (adjusted hazard ratio [aHR] = 0.31, 95% CI: 0.08–0.94, p = 0.0372) in the sustained virologic response (SVR) groups and ≥−1.696 (aHR = 0.09, 95% CI: 0.08–0.94, p = 0.0022) in the non-SVR group were less likely to develop HCC. Thus, circulating let-7i can be used for early CHC surveillance in patients with HCC risk after antiviral treatment.