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Updated: Sep 19, 2025

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Surviving Hepatitis C-Understanding Death and Survival Beyond Cure.

Paul J Clark1, Patricia C Valery2, Simone I Strasser3

  • 1Department of Gastroenterology, Princess Alexandra and Mater Hospitals, and Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Alimentary Pharmacology & Therapeutics
|June 19, 2025
PubMed
Summary

Curing hepatitis C virus (HCV) infection significantly reduces mortality, but factors like cirrhosis, non-sustained virological response, and age increase risks. Holistic care addressing mental health, comorbidities, and cancer screening is crucial for reducing long-term mortality post-HCV cure.

Keywords:
cirrhosisdirect‐acting antiviralhepatocellular carcinomaliver diseaseliver fibrosis

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Area of Science:

  • Hepatology
  • Virology
  • Public Health

Background:

  • Hepatitis C virus (HCV) cure via direct-acting antiviral (DAA) therapy reduces liver and all-cause mortality.
  • However, a residual risk of early mortality persists even after successful HCV eradication.
  • Identifying factors associated with cause-specific mortality post-DAA therapy is essential for comprehensive patient care.

Purpose of the Study:

  • To investigate the factors influencing cause-specific mortality in patients treated with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection.
  • To determine the long-term risks and predictors of mortality following successful HCV cure.

Main Methods:

  • A cohort of 3619 adult patients treated with DAAs between 2016-2021 was followed up to September 2023.
  • Population databases were utilized to obtain data on medication, healthcare utilization, and mortality outcomes.
  • Cause-specific mortality, including liver-related, self-harm/accidental poisoning, and respiratory causes, was the primary endpoint.

Main Results:

  • Among 3619 patients, 11.7% died, with liver disease (40.6%), self-harm/accidental poisoning (13.2%), and respiratory disease/lung cancer (12.3%) being leading causes.
  • Cirrhosis, FIB4 score > 3.25, non-sustained virological response (non-SVR), and age ≥ 60 years were significant predictors of liver-related mortality.
  • Non-SVR was associated with a threefold higher mortality rate. Factors like mental health medication use, loss to follow-up, and injection drug use increased risk for self-harm/accidental poisoning mortality.
  • Older age and diabetes were linked to increased mortality from extrahepatic cancers and cardiovascular disease.

Conclusions:

  • Liver-related death is a primary concern for cirrhotic patients post-HCV cure.
  • Achieving sustained virological response (SVR) is critical for reducing mortality.
  • Holistic HCV care strategies should incorporate mental health support, management of metabolic comorbidities, and targeted cancer screening, particularly for older individuals, to mitigate excess mortality.