Prediction of Hepatocellular Carcinoma in a Portuguese Population after Hepatitis C Cure: Comparative Accuracy of Noninvasive Tests (Transient Elastography, FIB-4, and aMAP)

Introduction: Chronic infection with hepatitis C virus (HCV) causes 25% of hepatocellular carcinoma (HCC) cases worldwide, a major cause of morbimortality even after sustained virologic response (SVR). Universal screening to all patients with advanced liver fibrosis is currently recommended. A risk-based strategy could improve the detection rate of early HCC and diminish the surveillance burden. Although several risk prediction models exist, exclusion of a subgroup of patients from surveillance has not yet been recommended. The objective of this study was the comparison of the predictive accuracy of transient elastography, FIB-4, and aMAP for HCC in HCV patients after SVR in Portugal. Methods: This was a multicentric retrospective study including patients with HCV after SVR. Comparative, univariate, multivariate, area under the ROC (receiver-operating characteristic) curve (AUC), and Youden's J-statistic analysis were performed. Results: HCC incidence was 4.2% (1.3/100 patient-years) after a median follow-up of 31 months with inclusion of 337 patients. All patients had a liver stiffness measurement (LSM) before SVR (considered the baseline), but only 148 (43.9%) had a transient elastography after SVR. FIB-4 and aMAP post-SVR were calculated in all patients. Multiple parameters positively correlated with HCC, but only age and baseline transient elastography remained as independent predictors in the multivariate analysis. The optimal cutoffs for prediction of HCC were baseline transient elastography 13.7 kPa, post-SVR transient elastography 16.5 and 15.8 kPa (first and last measurements, respectively), FIB-4 1.6, and aMAP 58. Baseline transient elastography revealed a fair accuracy in predicting HCC (AUC 0.776, p < 0.001), with the cutoff of 13.7 kPa presenting a sensitivity of 85% and a specificity of 69%. Regarding patients who were F3-4 at baseline (n = 162), almost one-third had a baseline LSM ≤13.7 kPa (n = 51, 31.5%), an FIB-4 ≤1.6 (n = 50, 30.9%), and an aMAP score ≤58 (n = 48, 29.6%), and these cutoffs presented an NPV of 98%, 94%, and 96%, respectively, when considering HCC development. Conclusion: Transient elastography (FibroScan) before SVR was a fair predictor of HCC, being more accurate than FIB-4 and aMAP. Transient elastography values≤13.7 kPa at baseline, FIB-4 ≤1.6 and aMAP ≤58 were the cutoffs considered of low risk for HCC in a Portuguese cohort of HCV patients after SVR with advanced fibrosis. aMAP score is a risk-based surveillance tool that could improve the current HCC screening strategy, but further validation is needed.