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. 2023;41(6):900-912.
doi: 10.1159/000533946. Epub 2023 Sep 13.

Global Epidemiology of Cirrhosis: Changing Etiological Basis and Comparable Burden of Nonalcoholic Steatohepatitis between Males and Females

Darren Tan  1 , Kai En Chan  1 , Zhen Yu Wong  2 , Cheng Han Ng  1 , Jieling Xiao  1 , Wen Hui Lim  1 , Phoebe Tay  1 , Ansel Tang  1 , Clarissa Elysia Fu  1 , Mark Muthiah  1   3 , Benjamin Nah  1   2 , Eunice X Tan  1   3 , Margaret L P Teng  1   3 , Mohammad Shadab Siddiqui  4 , Yock Young Dan  1   3 , Seng Gee Lim  1   3 , Rohit Loomba  5   6 , Daniel Q Huang  1   3   5
Affiliations

Global Epidemiology of Cirrhosis: Changing Etiological Basis and Comparable Burden of Nonalcoholic Steatohepatitis between Males and Females

Darren Tan et al. Dig Dis. 2023.

Abstract

Introduction: The etiology of liver diseases has changed significantly, but its impact on the comparative burden of cirrhosis between males and females is unclear. We estimated sex differences in the burden of cirrhosis across 204 countries and territories from 2010 to 2019.

Methods: We analyzed temporal trends in the burden of cirrhosis using the methodology framework of the 2019 Global Burden of Disease study. We estimated annual frequencies and age-standardized rates (ASRs) of cirrhosis incidence, death, and disability-adjusted life-years (DALYs) by sex, region, country, and etiology.

Results: In 2019, the frequency of incident cases, deaths, and DALYs due to cirrhosis was 1,206,125, 969,068, and 31,781,079 in males versus 845,429, 502,944, and 14,408,336 in females, respectively. From 2010 to 2019, the frequency of cirrhosis deaths increased by 9% in males and 12% in females. Incidence ASRs remained stable in males but increased in females, while death ASRs declined in both. Death ASRs for both sexes declined in all regions, except in the Americas where they remained stable. In 2019, alcohol was the leading cause of cirrhosis deaths in males, and hepatitis C in females. Death ASRs declined for all etiologies in both sexes, except in nonalcoholic steatohepatitis (NASH). The ratio of female-to-male incidence ASRs in 2019 was lowest in alcohol(0.5), and highest in NASH(1.3), while the ratio of female-to-male death ASRs was lowest in alcohol(0.3) and highest in NASH(0.8).

Conclusion: The global burden of cirrhosis is higher in males. However, incidence and death ASRs from NASH cirrhosis in females are comparable to that of males.

Keywords: Alcohol; Cirrhosis; Epidemiology; Etiology; Nonalcoholic steatohepatitis.

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Conflict of interest statement

R.L. receives funding support from NIAAA (U01AA029019), NIEHS (5P42ES010337), NCATS (5UL1TR001442), NIDDK (U01DK130190, U01DK061734, R01DK106419, P30DK120515, R01DK121378, R01DK124318), NHLBI (P01HL147835), and DOD PRCRP (W81XWH-18-2–0026). R.L. serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Co-founder of LipoNexus Inc.

S.G.L. has received educational or research funding from Abbott, Merck Sharpe and Dohme, Gilead Sciences. S.G.L. has served as an advisory board member for Gilead Sciences, Merck Sharpe and Dohme, Abbvie, and Abbott, and has served as a speaker for Gilead Sciences, Abbott, Merck Sharpe and Dohme, Roche. D.H. has served as an advisory board member for Eisai and receives funding support from Singapore Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01).

Figures

Fig. 1.
Fig. 1.
a Frequency of incident cirrhosis cases in males versus females from 2010 to 2019, by etiology of liver disease. b Frequency of cirrhosis-related deaths in males versus females from 2010 to 2019, by etiology of liver disease. c Frequency of cirrhosis-related deaths in males versus females in 2019, by etiology of liver disease. d Frequency of cirrhosis-related deaths in males versus females in 2019, by World Health Organization region. e Contribution of global cirrhosis-related deaths in male versus females in 2019, by etiology of liver disease.
Fig. 2.
Fig. 2.
a Age-standardized incidence rates (ASIRs) of cirrhosis in males versus females from 2010 to 2019 by etiology of liver disease. b Age-standardized death rates (ASDRs) of cirrhosis in males versus females from 2010 to 2019 by etiology of liver disease. c Ratio of female-to-male age-standardized incidence rates (ASIRs) of cirrhosis from 2010 to 2019 by etiology of liver disease. d Ratio of female-to-male age-standardized death rates (ASDRs) of cirrhosis from 2010 to 2019 by etiology of liver disease. e Age-standardized death rates (ASDRs) of cirrhosis in males versus females in 2019 by World Health Organization region. f Ratio of female-to-male age-standardized death rates (ASDRs) of cirrhosis from 2010 to 2019 by World Health Organization region.
Fig. 3.
Fig. 3.
a Ratio of female-to-male age-standardized death rates (ASDRs) of cirrhosis (from all major etiologies) in 2019, by country/territory. b Ratio of female-to-male age-standardized death rates (ASDRs) of NASH cirrhosis in 2019, by country/territory.
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