Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure

Background & Rationale: Around 750.000 patients/year will be cured from hepatitis C-virus (HCV)-infection until 2030. Those with compensated advanced chronic liver disease (cACLD) remain at risk for hepatic decompensation and de-novo hepatocellular carcinoma (HCC). Algorithms have been developed to stratify risk early after cure, however, data on long-term outcome and the prognostic utility of these risk stratification algorithms at later timepoints are lacking. Main Results: We retrospectively analysed a cohort of 2335 cACLD-patients (LSM≥10kPa) who achieved HCV-cure by interferon-free therapies from 15 European centres (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes). During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate [IR]: 0.74%/year, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de-novo HCC (IR: 1.60%/year, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time. Baveno VII criteria to exclude (FU-LSM <12kPa & FU-PLT >150 G/L) or rule-in (FU-LSM ≥25kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the grey-zone (i.e., patients meeting none of the above criteria). Published HCC risk stratification algorithms identified high- and low-incidence groups, however, the size of the latter group varied substantially (9.9%-69.1%). A granular 'HCC-SVR' model was developed to inform on an individual patient's HCC-risk after HCV-cure. Conclusion: In patients with cACLD, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long-term (>3 y). One-time post-treatment risk stratification based on non-invasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.