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Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure
Georg Semmler1,2, Sonia Alonso López3,4,5, Monica Pons6
1Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
Insights
Hepatitis C cure in advanced liver disease patients shows constant risks for decompensation and HCC long-term. Post-treatment risk stratification using noninvasive criteria remains prognostic over time.
Area of Science:
- Hepatology
- Virology
- Gastroenterology
Background:
- Hepatitis C virus (HCV) infection affects millions, with many achieving cure.
- Patients with compensated advanced chronic liver disease (cACLD) post-HCV cure face risks of hepatic decompensation and hepatocellular carcinoma (HCC).
- Existing risk stratification algorithms lack long-term outcome data and prognostic utility assessment at later time points.
Purpose of the Study:
- To evaluate long-term risks of hepatic decompensation and de novo HCC after HCV cure in cACLD patients.
- To assess the prognostic utility of current risk stratification algorithms over time.
- To develop improved models for predicting HCC risk post-HCV cure.
Main Methods:
- Retrospective analysis of 2335 cACLD patients (liver stiffness measurement ≥10 kPa) achieving HCV cure with interferon-free therapies across 15 European centers.
- Median follow-up of 6 years.
- Assessment of Baveno VII criteria for clinically significant portal hypertension (CSPH) and published HCC risk stratification algorithms; development of a new "HCC-sustained virologic response" model.
Main Results:
- During follow-up, 3.6% experienced hepatic decompensation and 7.8% developed de novo HCC, with linear, constant risks over time.
- Baveno VII criteria stratified hepatic decompensation risk, with CSPH probability discriminating outcomes in the gray zone.
- Published HCC algorithms showed variable performance; the new model aims for granular risk prediction.
Conclusions:
- Hepatic decompensation and HCC risks remain constant and linear long-term (>3 years) after HCV cure in cACLD patients.
- One-time post-treatment risk stratification using noninvasive criteria provides sustained prognostic information.
- Proportional hazards indicate the continued relevance of initial risk assessments over time.
Background And Aims:
Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking.
Approach And Results:
We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (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: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) 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 gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure.
Conclusions:
In patients with compensated advanced chronic liver disease, 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 noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.
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