Trends in Mortality After the Roll-Out of Directly Acting Antivirals for Hepatitis C in England Using Linked...

Directly acting antivirals (DAAs) revolutionised hepatitis C virus (HCV) treatment, offering higher cure rates. We aimed to quantify life expectancy (LE) differences between treated and untreated individuals diagnosed with HCV and assess the contributions of age and causes of death to these differences. We used routine HCV surveillance data linked with UK mortality records. Individuals contributed person-time from age 15 or the earliest HCV diagnosis, whichever was later, and were classified as treated six months post-treatment initiation. The study was divided into two periods: 2015-2018 (Period 1), representing early DAA roll-out targeting advanced liver disease, and 2019-2022 (Period 2). We used non-parametric survival analysis methods and mortality decomposition methods to estimate LE differences, and age- and cause-specific contributions to LE differences. A total of 92,920 individuals contributed 322,570 untreated and 200,581 treated person-years of observation, and 13,294 deaths to the analyses. In Period 1, there was an 8.5-year LE advantage at age 15 for treated females (95% CI: 5.4-11.5) and 8.9 years for treated males (95% CI: 5.6-12.2). In Period 2, this declined to 6.7 (95% CI: 3.3-10.2) and 5.3 (95% CI: 3.0-7.6), respectively. The narrowing gap was driven by rising deaths from suicide, alcohol, and drug misuse in the treated population and corresponding declines in the untreated population. Treated individuals with HCV had consistently higher LE, though the advantage decreased over time. We hypothesise that the early prioritisation of individuals with cirrhosis resulted in a relatively healthier untreated population (i.e., fewer cirrhotic cases) in the later period.