Non-invasive risk stratification after HCV-eradication in patients with advanced chronic liver disease

Background & aims: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of non-invasive surrogates of portal hypertension (liver stiffness measurement (LSM) by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio (VITRO)) for development of hepatic decompensation and hepatocellular carcinoma in patients with pre-treatment advanced chronic liver disease (ACLD) who achieved HCV-cure. Approach & results: 276 patients with pre-treatment ACLD and information on pre- and post-treatment (follow-up (FU))-LSM and -VITRO were followed for a median of 36.6 months after the end of interferon-free therapy. FU-LSM (AUROC:0.875(95%CI:0.796-0.954)) and FU-VITRO (AUROC:0.925 (95%CI:0.874-0.977)) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU-LSM<12.4kPa and/or FU-VITRO<0.95) to rule-out clinically significant portal hypertension (CSPH, HVPG≥10mmHg) at FU assigned the majority (57.3%) of patients to the low-risk group - none of these patients developed hepatic decompensation. In contrast, in patients in whom FU-CSPH was ruled-in (FU-LSM>25.3kPa and/or FU-VITRO>3.3; 25.0% of patients), the risk of hepatic decompensation at 3-years post-treatment was high (17.4%). Patients within the diagnostic gray-zone for FU-CSPH (17.8% of patients) had a very low-risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n=86) and external (n=162) cohort. Conclusion: FU-LSM/FU-VITRO are strongly and independently predictive of post-treatment hepatic decompensation in HCV-induced ACLD. An algorithm combining these non-invasive markers not only rules-in or rules-out FU-CSPH, but also identifies populations at negligible vs. high-risk for hepatic decompensation. FU-LSM/FU-VITRO are readily accessible and enable risk stratification after SVR, and thus, facilitate personalized management.