Abstract

Background:

Alcohol related harms to adolescents and young adults (AYAs) are on the rise and a priority group for identification and treatment to prevent progression of alcohol-associated liver disease (ALD). Females are at higher risk of developing ALD compared to males secondary to biologic and social-cultural factors. However, whether this sex difference persists after an episode of acute alcoholic hepatitis (AH) is unknown. This study aimed to evaluate the association between female sex and incident cirrhosis after first presentation of AH in the general population.

Methods:

Retrospective population-based cohort study of routinely collected healthcare data from Ontario, Canada. AYAs (aged 13-39) with a first presentation of AH as the most responsible diagnosis at emergency room (ER) or hospital admission were identified from 2002 to 2021 and followed to 2022. Incident cirrhosis was defined based on validated coding. The association between female sex and incident cirrhosis from 6 months post-discharge onward was evaluated using competing risks regression where liver transplant (LT) and death were competing events to cirrhosis with adjustment for age, income quintile, rurality, co-morbid illness, immigration status, and disease severity (ER vs. inpatient).

Results:

Overall n=3,340 AYAs with first presentation of AH were identified; median age at presentation was 33 years (IQR 28-36), n=1,190 (36%) were female, n=4,717 (70%) had healthcare encounters related to alcohol within the 2-years prior to AH presentation, n=2,801 (70%) required hospital admission, and n=624 (19%) had cirrhosis and/or decompensation at index. Of those requiring hospital admission, the median length of stay was 5 days (IQR 3-8), n=465 (17%) required ICU level care, n=76 (2%) required hemodialysis and n=91 (3%) died before discharge. After a median follow-up of 4 years (IQR 2-9 years), n=603 (22%) died and n=7 (<1%) received LT. In total n=2,690 (81%) were alive and without cirrhosis at 6 months post discharge of which n=789 (29%) were diagnosed with cirrhosis during follow-up (n=325 [35%] in females; n=464 [26%] in males, P <.001), and of those, n=320 (41%) were decompensated. After adjusted competing risks regression, female sex was associated with a 47% higher subhazard of cirrhosis compared to male sex (sHR 1.47, 95% CI 1.23-1.76, P <.001) in addition to older age (sHR 1.05, 95% CI 1.03-1.06) and higher co-morbidity (sHR 1.36, 95% CI 1.01-1.82; Table). The cumulative incidence of death at 1-, 5-, and 10-years was 9%, 22%, and 31% respectively without difference between sexes (P=.06).

Conclusion: Almost 1/3^rd of young adults with first presentation of AH develop cirrhosis after a median of 4 years and this risk is 50% higher for females vs. males. Whether this is secondary to differences in biologic or sociocultural factors such as ongoing alcohol use or engagement in medical care or alcohol use disorder treatment requires further investigation.