Society: AASLD

Background: Cirrhosis is a major contributor of morbidity and mortality in patients with chronic liver disease globally. The disease burden of viral-related cirrhosis has decreased, related to advancements in prevention and treatments while the prevalence of non-alcoholic fatty liver disease and alcohol-associated cirrhosis has increased mirroring the metabolic disease epidemic. Nevertheless, the relative implication of the transition in the predominant etiology of cirrhosis has yet to be examined between males and females. This study aims to present sex differences in the disease burden of cirrhosis from 2010-2019.

Methods: Using the Global Burden of Disease Study 2019, we evaluated the temporal trends of cirrhosis incidence between the sexes. Yearly frequencies and age-standardized rates (ASR) of incidence, death, and disability-adjusted life-years (DALYs) associated with cirrhosis from 2010-2019 were estimated and stratified by sex, region, country, socio-demographic index (SDI), and cirrhosis etiology.

Results: In 2019, the overall burden of cirrhosis was higher in males compared to females. There were 1,206,125 incident cases, 969,068 deaths, and 31,781,079 DALYs due to cirrhosis in males, and 845,429 incident cases, 502,944 deaths, and 14,408,336 DALYs due to cirrhosis in females, respectively (Figure 1A-D). From 2010-2019, there was an 11% increase in incident cirrhosis cases in males and a 16% increase in females. The frequency of cirrhosis-related deaths also increased by 9% in males and 12% in females. Incidence ASR of cirrhosis increased in females while remaining stable in males. However, death ASRs declined in both males and females in all regions except for the Americas where it remained stable. The largest increase in incident cirrhosis cases was in low SDI countries for both males (+37%) and females (+32%). While the leading cause of incident cirrhosis cases was HCV in both sexes, NASH was the fastest-growing etiology of incident cirrhosis cases in both males (+23%) and females (+30%). The leading cause of cirrhosis-related deaths was alcohol and HCV in males and females respectively (Figure 1E). Furthermore, death ASRs decreased for all etiologies in both sexes, except for NASH-related cirrhosis which remained stable.

Conclusion: In summary, the global burden of cirrhosis is substantially higher in males compared to females. Age-adjusted mortality declined for all etiologies of liver disease for males and females, except in NASH. The age-adjusted incidence rates of NASH cirrhosis in females exceeded that of males, while age-adjusted mortality rates in females approached that of males. Measures are required to tackle obesity and diabetes to reduce the global burden of NASH cirrhosis in both males and females.

<b>Figure 1 </b><br /> <b>(A</b>): Frequency of incident cirrhosis cases in males versus females from 2010 to 2019, by etiology of liver disease<br /> <b>(B</b>): Frequency of cirrhosis-related deaths in males versus females from 2010 to 2019, by etiology of liver disease<br /> <b>(C): </b>Frequency of cirrhosis-related deaths in males versus females in 2019, by etiology of liver disease<br /> <b>(D): </b>Frequency of cirrhosis-related deaths in males versus females in 2019, by World Health Organization region<br /> <b>(E): </b>Contribution of global cirrhosis-related deaths in male versus females in 2019, by etiology of liver disease

Figure 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

Rebecca Wenling Zeng

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