BACKGROUND & AIMS:The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. METHODS:HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. RESULTS:Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. CONCLUSIONS:Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. LAY SUMMARY:The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.