A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data

Background and Aims: Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs.

Design: This was a self-controlled case-series study.

Setting: Scotland, 1 January 2015-30 November 2020.

Participants: The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes.

Measurements: Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter.

Findings: A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end.

Conclusions: Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms.