Theme: Clinical Research Year: 2021
Background: Chronic hepatitis C virus (HCV) infection is associated with mortality due to extrahepatic manifestations (EHM). The sustained virologic response (SVR) following the highly effective directacting antivirals (DAA) has been linked to decreased all-cause and liver-related mortality. However, evidence on the impact of DAA on EHM-related mortality is lacking. Methods: The British Columbia (BC) Hepatitis Testers Cohort includes ~1.3 million people tested for HCV and is linked with various administrative health data. We compared three groups of individuals: treated & SVR, treated & no-SVR, and untreated. EHM-mortality included deaths due to diabetes, rheumatoid arthritis, cardiovascular, cerebrovascular, renal and neurocognitive diseases. Eligible individuals were followed to the earliest of 1) EHM-related-death; 2) other death, or 3) end of study (2019/12/31). To adjust for differences in baseline characteristics, we estimated the inverse probability of treatment weights (IPTW). Then, we used IPTW-weighted multivariable subdistributional hazards model adjusting for competing risk and confounders. Results: Study population included 10,694 treated (10,254 SVR, 440 no-SVR) and 10,694 untreated individuals. Among untreated people, 44.4% had history of injection drug use (IDU). Among those who received treatment, 33.4% of those with SVR and 50.9% of those with no-SVR had history of IDU. EHM-mortality rate was 5.86 per 1,000 PYFU (95% confidence interval [CI] 5.00-6.87) for treated & SVR; 25.32 per 1,000 PYFU (95% CI 16.67-38.45) for treated & no-SVR; and 29.40 per 1,000 PYFU (95% CI 27.21-31.76) for untreated individuals. In multivariable model, treated & SVR group had the greatest reduction in EHM-mortality (adjusted hazard ratio [aHR] 0.16, 95% CI 0.13-0.20), followed by treated & no-SVR group (aHR 0.57, 95% CI 0.34-0.94) compared to untreated group. Conclusion: Virologic cure of HCV following DAA treatment was associated with a significant reduction in EHMmortality. This highlights the crucial need of providing diagnosis and treatment for people living with HCV infection to reduce extrahepatic mortality. Disclosure of Interest Statement: DJ is supported by the CIHR Frederick Banting and Charles Best Doctoral Award and the Canadian Network on Hepatitis C PhD fellowship. MEK is supported by the Michael Smith Foundation for Health Research Scholar award and holds research grants from the Natural Sciences and Engineering Research Council of Canada and BC SUPPORT Unit. Over the past 3 years, MEK has received consulting fees from Biogen Inc (unrelated to this project). SB advises and is on the speakers’ bureau for Gilead. MK has received grant/research support from Roche, Merck, Siemens, Boehringer Ingelheim and Hologic. SW, JW, MJD, HV, MB, PA, MP AY, MA, HS, YA, NJ have no conflicts of interest to declare.
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