Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study
Authors: Hamill Victoria , Wong Stanley , Benselin Jennifer , Krajden Mel , Hayes Peter C , Mutimer David , Yu Amanda , Dillon John F , Gelson William , Velásquez García Hector A , Yeung Alan , Johnson Philip , Barclay Stephen T , Alvarez Maria , Toyoda Hidenori , Agarwal Kosh , Fraser Andrew , Bartlett Sofia , Aldersley Mark , Bathgate Andy , Binka Mawuena , Richardson Paul , Morling Joanne R , Ryder Stephen D , MacDonald Douglas , Hutchinson Sharon , Barnes Eleanor , Guha Indra Neil , Irving William L , Janjua Naveed Z , Innes Hamish 
Published: August 2023

Abstract

Objectives
To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population.

Design
Population based cohort study.

Setting
British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only).

Participants
21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019.

Main outcome measures
Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates.

Results
1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates.

Conclusion
Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.