Related Experiment Video
Updated: Jun 18, 2025
A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
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
Patients cured of hepatitis C virus (HCV) infection with advanced liver disease still face long-term risks of liver decompensation and hepatocellular carcinoma (HCC). Risk stratification after HCV cure remains valuable for predicting these outcomes over time.
Area of Science:
- Hepatology
- Virology
- Oncology
Background:
- Hepatitis C virus (HCV) infection affects millions globally, with an estimated 750,000 patients cured annually by 2030.
- Patients with compensated advanced chronic liver disease (cACLD) post-HCV cure remain at risk for hepatic decompensation and de novo 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 the long-term risks of hepatic decompensation and de novo HCC in patients with cACLD after HCV cure.
- To assess the prognostic utility of noninvasive risk stratification criteria, including Baveno VII, in predicting long-term outcomes.
- To develop and validate a granular model for individualizing HCC risk assessment post-HCV cure.
Main Methods:
- Retrospective analysis of 2335 patients with cACLD (liver stiffness measurement ≥10 kPa) achieving HCV cure via interferon-free therapies across 15 European centers.
- Median follow-up of 6 years to assess incidence rates and cumulative incidence of hepatic decompensation and de novo HCC.
- Application and evaluation of Baveno VII criteria and published HCC risk stratification algorithms; development of a novel 'HCC-sustained virologic response' model.
Main Results:
- During a median 6-year follow-up, hepatic decompensation occurred in 3.6% and de novo HCC in 7.8% of patients, with linear risk progression over time.
- Baveno VII criteria effectively stratified hepatic decompensation risk, with proportional hazards observed over time.
- Published HCC risk models showed variability in identifying low-risk groups; a new granular model was developed to better inform individual HCC risk.
Conclusions:
- The risks of hepatic decompensation and HCC remain constant and linear over the long term (>3 years) in patients with cACLD after HCV cure.
- One-time post-treatment risk stratification using noninvasive criteria provides sustained prognostic information.
- Continued monitoring and refined risk stratification are crucial for managing long-term complications in this patient population.
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.
Related Concept Videos
01:29Chronic Pancreatitis II: Collaborative Care
Assessment:
01:24Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...