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UBC Theses and Dissertations

Clearance, reinfection and re-clearance of hepatitis C Islam, Nazrul


Purpose: Despite the availability of effective treatments for Hepatitis C virus (HCV) infection, public health experts face challenges to intervening effectively, in part due to gaps in understanding the natural history of HCV. To address these knowledge gaps, the current dissertation uses a large population-based cohort in British Columbia (BC), Canada, to examine spontaneous clearance, reinfection, and spontaneous clearance of reinfection (i.e., re-clearance) of HCV. Methods: This study draws data from the BC Hepatitis Testers Cohort that includes all individuals tested for HCV in BC (1990-2013), with linkages to data on their medical visits, hospitalizations, and prescription drugs. HCV-positive individuals with ≥1 valid HCV-PCR test on/after HCV diagnosis (n=46,783) were included, with varying eligibility criteria for each of the three primary analyses. Logistic regression and Cox proportional hazards regression models were used, as applicable. Results: The proportion of primary spontaneous clearance, reinfection, and re-clearance was 25.1% (11,737 of 46,783), 7.6% (452 of 5,915), and 33.9% (121 of 357), respectively. Chapter 2 shows that the likelihood of spontaneous clearance of primary HCV infection is lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94) and higher in females (aOR: 1.61, 95% CI: 1.54-1.68). Chapter 3 shows a higher reinfection risk in the spontaneous clearance group compared to sustained virological response group (adjusted Hazard Ratio [aHR]: 2.71, 95% CI: 2.0-3.68), those coinfected with HIV (aHR: 2.25, 95% CI: 1.78-2.85), and people who inject drugs [PWID] (aHR: 1.53, 95% CI: 1.21-1.92). Among PWID, opioid substitution therapy [OST] (aHR: 0.73, 95% CI: 0.54-0.98) and mental health counseling (aHR: 0.71, 95% CI: 0.54-0.92) were associated with a lower HCV reinfection risk. Chapter 4 shows that, among those who spontaneously cleared the primary infection, the likelihood of HCV re-clearance was 54% lower (aHR: 0.46, 95% CI: 0.24-0.86) if reinfected with a heterologous HCV genotype. Conclusions: People with compromised immunity may be prioritized for HCV treatment allocation. The positive impacts of scaled-up HCV treatment might be enhanced if accompanied by appropriate harm reduction programs to prevent reinfections among PWID with a view to achieving World Health Organization’s goal of HCV elimination.

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