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CHAIN Cohort: Prospective Multicenter Study of MASLD With Serial Liver Stiffness Assessments in Cardiovascular Care.

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Long-Term Mortality Following Hepatitis C Cure in a Real-World Multinational Cohort.

Fanpu Ji1, Sally Tran2, Hidenori Toyoda3

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Liver International : Official Journal of the International Association for the Study of the Liver
|February 22, 2026
PubMed
Summary

Hepatitis C cure with direct-acting antivirals (DAA) is linked to better outcomes, but detailed mortality risks post-cure need clarification. This study identified age, sex, cirrhosis, and diabetes as key mortality risk factors in DAA-cured patients.

Keywords:
chronic hepatitis Cdirect‐acting antiviral agentsdisparitiesmortalitysustained virological response

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Area of Science:

  • Hepatology
  • Virology
  • Public Health

Background:

  • Direct-acting antiviral (DAA) agents effectively cure Hepatitis C Virus (HCV) infection.
  • While DAA-mediated HCV cure correlates with improved patient outcomes, comprehensive data on mortality risk factors post-cure remain limited.
  • Understanding these risk factors is crucial for long-term patient management and public health strategies.

Purpose of the Study:

  • To investigate detailed mortality rates and identify associated risk factors in patients achieving sustained virological response (SVR) after DAA treatment for HCV.
  • To provide granular data on mortality and causes of death across different patient subgroups, including those with and without cirrhosis.

Main Methods:

  • Retrospective analysis of 10,034 HCV patients with DAA-SVR from 39 international centers.
  • Calculation of all-cause mortality rates per 1000 patient-years (PY).
  • Stratification by cirrhosis status (non-cirrhosis, compensated, decompensated) and identification of mortality risk factors (age, sex, diabetes).

Main Results:

  • Overall mortality rate was 10.4 per 1000 PY, with significantly higher rates in decompensated cirrhosis (60.0 per 1000 PY).
  • Five-year cumulative survival was 95.1% overall, dropping to 73.9% in decompensated cirrhosis.
  • Key mortality risk factors identified: age > 65 (3.2-fold), male sex (1.5-fold), decompensated cirrhosis (7.6-fold), and baseline diabetes mellitus (DM) (1.5-fold).
  • Liver-related deaths predominated in decompensated cirrhosis, while non-liver-related deaths were more common in non-cirrhosis and compensated cirrhosis groups.

Conclusions:

  • Significant differences in mortality and causes of death exist among DAA-SVR patients based on age, sex, fibrosis stage, and DM status.
  • These findings support the need for precision medicine approaches in managing HCV patients post-cure.
  • The granular subgroup data can inform individualized care, future epidemiological modeling, and public health planning.