• Maryam Alavi, Matthew G Law, Heather Valerio, Jason Grebely, Janaki Amin, Behzad Hajarizadeh, Christine Selvey, Jacob George, and Gregory J Dore.
• The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address: msalehialavi@kirby.unsw.edu.au.
• J. Hepatol. 2019 Aug 1; 71 (2): 281-288.

Background & AimsPopulation-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales, Australia.MethodsHCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively.ResultsAmong 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04-1.05], 1.08 [95% CI 1.07-1.08], 1.07 [95% CI 1.06-1.07], and 1.05 [95% CI 1.04-1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95-0.99] and 0.96 [95% CI 0.94-0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97-1.03] and 1.01 [95% CI 1.00-1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14-3.58).ConclusionsIn the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities.Lay SummaryRising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.Copyright © 2019 European Association for the Study of the Liver. All rights reserved.

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