Trends in cause-specific mortality in HIV-hepatitis C coinfection following hepatitis C treatment scale-up

Abstract

Objective: Hepatitis C virus (HCV) treatment may reduce liver-related mortality but with competing risks, other causes of mortality may undermine benefits. We examined changes in cause-specific mortality among HIV-HCV coinfected patients before and after scale-up of HCV treatment.

Design: Prospective multicentre HIV-HCV cohort study in Canada.

Methods: Cause-specific deaths, classified using a modified 'Coding of Cause of Death in HIV' protocol, were determined for two time periods, 2003-2012 and 2013-2017, stratified by age (20-49; 50-80 years). Comparison of trends between periods was performed using Poisson regression. To account for competing risks, multinomial regression was used to estimate the cause-specific hazard ratios of time and age on cause of death, from which end-stage liver disease (ESLD)-specific 5-year cumulative incidence functions were estimated.

Results: Overall, 1634 participants contributed 8248 person-years of follow-up; 273 (17%) died. Drug overdose was the most common cause of death overall, followed by ESLD and smoking-related deaths. In 2013-2017, ESLD was surpassed by drug overdose and smoking-related deaths among those aged 20-49 and 50-80, respectively. After accounting for competing risks, comparing 2003-2012 to 2013-2017, ESLD deaths declined (adjusted hazards ratio: 0.18, 95% confidence interval 0.05-0.62). However, both early and late period cumulative incidence functions demonstrated increased risk of death from ESLD for patients with poor HIV control and advanced fibrosis.

Conclusion: The gains made in overall mortality with HCV therapy may be thwarted if modifiable harms are not addressed. Although ESLD-related deaths have decreased over time, treatment should be further expanded, prioritizing those with advanced fibrosis.

Fig. 1

Unadjusted cause-specific event rates per 1000 person-years by age group and time period.

Fig. 2

Cause-specific adjusted hazard ratios (95% confidence intervals) for time period, hepatitis C virus RNA and age on end-stage liver disease, smoking-related, overdose, other and unknown causes of death.

Fig. 3

Early and late period 5-year end-stage liver disease-specific cumulative incidence functions by reference group (a, b and c) stratified by age group (20–49 and 50–80) and hepatitis C virus RNA status [positive (+) and negative (−)].