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Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study
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June 04, 2021
In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment.
We found that SVR from DAAs compared to no-treatment is associated with an 81% reduction in all-cause mortality, a 78% reduction in liver-related, and a 74% reduction in drug-related mortality risk. Within the treated group, SVR compared to no-SVR was associated with slightly higher reduction in all-cause (81%), and liver-related mortality (87%), but a lower reduction in drug-related (64%) mortality risk. The reduction in mortality risk was lower among people with cirrhosis. Cirrhosis and older age (≥40 years) was associated with higher liver-related mortality risk while IDU, younger age, problematic alcohol use, and HIV/HBV co-infections were associated with higher drug-related mortality risk. These findings indicate that DAAs will have a major impact on reducing mortality risk among people living with HCV; however, people with substance use disorder and HCV will need further integrated support services to reduce drug-related harms to maintain the benefits achieved through curative DAAs.
Other factors associated with increased all-cause mortality risk were cirrhosis at treatment initiation (aHR 2.18; 95% CI 1.99-2.65), older age (40-59 years aHR 1.42; 95% CI 1.08-1.93; ≥60 years aHR 2.21; 95% CI 1.68-3.03 compared to ≤29 years), being male (aHR 1.35; 95% CI 1.23-1.48), HIV coinfection (aHR 1.58; 95% CI 1.35-1.85), and problematic alcohol use (aHR 1.34; 95% CI 1.22-1.48). There were some notable differences in factors associated with liver-related and drug-related mortality. Cirrhosis was associated with a higher risk of liver-related mortality (asHR 6.79; 95% CI 5.71-8.07) while IDU was associated with a significantly higher risk of drug-related mortality (asHR 3.35; 95% CI 2.68-4.19). In addition, older age was associated with higher liver-related mortality while younger age was associated with higher drug-related mortality (Table 4).
Highlights
• Chronic HCV is associated with a higher risk of mortality.
• SVR from DAAs was associated with a significant reduction in the risk of all-cause, liver- and drug-related mortality.
• Older age and cirrhosis were associated with higher risk of liver-related mortality.
• Younger age, injection drug use, and problematic alcohol use were associated with higher risk of drug-related mortality.
Background & Aims
We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada.
Methods
We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality.
Results
Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality.
Conclusions
DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs.
Lay summary
We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.
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