Young Women Face Worse Long-Term Alcohol-Associated Hepatitis Outcomes Than Men

New research is sounding the alarm on increasing rates of alcohol-associated hepatitis (AH) among adolescents and young adults, additionally highlighting notable sex disparities for long-term liver-related outcomes.1

Findings from the population-based study of more than 3000 patients 13-39 years of age in Canada suggest rapid increases in the rates of AH in this patient population over the past 2 decades, especially among women. Despite numerically more males being affected by AH, females had greater rates of liver-related mortality and were at an approximately 50% increased risk of developing cirrhosis.1

According to alcohol-associated liver disease practice guidance from the American Association for the Study of Liver Diseases, women have a greater risk of liver injury compared with men for any level of drinking. Additionally, while rates of alcohol use disorder and high-risk drinking have risen in the US in recent years, some of the greatest increases have been observed among women.2

“Given the surging rates of AH among adolescents and young adults, there is an urgent need to identify risk groups and short- and long-term outcomes to facilitate targeted interventions and chronic disease management plans,” Jennifer Flemming, MD, an associate professor of medicine and public health sciences at Queen's University, and colleagues wrote.1 “The influence of sex on the development of major liver-related outcomes, such as cirrhosis and decompensation, among adolescents and young adults with AH is understudied.”

To define the sex-specific epidemiology of AH in adolescents and young adults as well as the association between female sex and liver-related outcomes, investigators conducted a population-based retrospective cohort study in Ontario, Canada, using data from ICES, an independent, nonprofit research institute that houses an electronic repository of datasets for all Ontario residents eligible for the province’s single-payer health care system.1

Data on adolescents and young adults 13-39 years of age with an incident diagnosis of alcohol-associated hepatitis without a history of cirrhosis and/or decompensation were identified through inpatient hospital admissions and emergency department records and included in the analysis. Incident diagnoses were captured from January 1, 2002, to December 31, 2021.1

Sex was the primary exposure obtained from the Registered Persons Database. The outcomes of interest included all-cause mortality with death date obtained from the Registered Persons Database up to December 31, 2022.1

A total of 3340 adolescents and young adults with alcohol-associated hepatitis were identified and included in the analysis. Among the cohort, the median age was 33 (interquartile range [IQR], 28-36) years and 64% of patients were male. The median follow-up was 5 (IQR, 2-10) years, during which time most participants required hospitalization (74%) with a median length of stay of 4 (IQR, 3-8) days.1

Investigators noted rates of alcohol-associated hepatitis increased by 8% per year (rate ratio [RR], 1.08; 95% CI, 1.07-1.09; P <.001), with yearly rates increasing faster among females (RR, 1.11; 95% CI, 1.09-1.12) than males (RR, 1.07; 95% CI, 1.06-1.07).1

The cumulative incidence of death was 6.9% at 1 year (95% CI, 6.2%-7.9%); 18.9% at 5 years (95% CI, 17.4%-20.3%); 29.4% at 10 years (95% CI, 27.5%-31.4%); and 47.7% at 20 years (95% CI, 43.5%-51.8%). However, when stratified by sex, investigators did not observe any association with overall mortality. Additionally, in competing risks regression, there was no association between female sex and overall mortality (subdistribution hazard ratios [sHR], 1.10; 95% CI, 0.95-1.27).1

A total of 2374 individuals (71%) were alive without cirrhosis 6 months after their initial alcohol-associated hepatitis presentation. Of those, 527 (22%) developed incident cirrhosis and/or decompensation after a median follow-up of 4 (IQR, 2-9) years (37% females vs 29% males; P <.001).1

Further analysis revealed female sex was independently associated with a 47% greater subhazard of cirrhosis and/or decompensation (sHR, 1.47; 95% CI, 1.23-1.76; P <.001). Investigators also pointed out the cumulative incidence of liver-related mortality at 10 years was higher among females (11.0%; 95% CI, 8.3%-14.2%) than males (6.9%; 95% CI, 5.4%-8.6%; P = .01).1

They acknowledged multiple limitations to these findings, including the use of ICD codes to define AH; the inability to account for AH treatment and how this may affect outcomes in the present study; and the lack of data available regarding the treatment of alcohol use disorder, quantity of alcohol consumption, obesity, race and ethnicity, marital status, or social supports, which may be associated with the development of AH and study outcomes.1

“These data support the need to develop early identification and treatment for those at risk for AH and multidisciplinary management after their first presentation,” investigators concluded.1 “Furthermore, the increase of AH among adolescents and young adults highlights the need to develop clinical trials and observational studies with a sex or gender approach to best support this younger vulnerable population.”

References

1. Flemming JA, Djerboua M, Chapman O, Ayonrinde O, Terrault NA. Epidemiology and Outcomes of Alcohol-Associated Hepatitis in Adolescents and Young Adults. JAMA Netw Open. doi:10.1001/jamanetworkopen.2024.52459
2. Crabb DW, Im GY, Szabo G, et al. Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. doi:10.1002/hep.30866