Surviving Hepatitis C-Understanding Death and Survival Beyond Cure

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.