Women at 50% Greater Risk Progressing from Alcoholic Hepatitis to Cirrhosis than Men

Jennifer Flemming, MD, FRCPC

Approximately 3 in 10 young adults first presenting with acute alcoholic hepatitis develop cirrhosis within a median of 4 years, according to new data.¹ What’s more, this severely at-risk population has a significantly disparate trend among sexes: women are 47% more likely to develop cirrhosis than men.

In new findings from a study presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, a multinational team of experts reported that women aged 13 - 39 years old were significantly more likely than their male counterparts to progress from acute alcoholic hepatitis to cirrhosis after first presentation. The findings additionally showed patients who progressed to cirrhosis were additionally more likely to be older and report multiple comorbidities than their male counterparts.

Investigators led by Jennifer Flemming, MD, FRCPC, associate professor of Medicine and Public Health Sciences at Queen's University, sought to evaluate the link between female sex and incident cirrhosis following first presentation of acute alcoholic hepatitis—a condition that which is increasing relative to trends of overall alcohol-associated liver disease in the US.

Their retrospective, population-based cohort analysis included health care data from adolescents and young adults aged 13 - 39 years old in Ontario, Canada, who first presented with acute alcoholic hepatitis in an emergency room or hospital admission between 2002 - 2021. Patients were followed up until 2022, with incident cirrhosis serving as a primary endpoint.

The team adjusted the likelihood of sex-specific progression to cirrhosis based on age, income quintile, rurality, comorbid illnesses, immigration status, and disease severity—the last component being measured as emergency room or inpatient care.

Among the 3340 adolescents and young adults first presenting with acute alcoholic hepatitis during the study period, median patent age was 33 years old; approximately one-third (36%) were female. Seven in 10 (70%) reported a healthcare encounter related to alcohol use within ≤2 years of their acute alcoholic hepatitis presentation. Another 70% required hospital admission, and 19% had cirrhosis and/or decompensation at index.

Median length of hospital stay was 5 days; 17% of those admitted required intensive care unit admission; 2% required hemodialysis; 3% died prior to discharge.

Median follow-up period was 4 years (interquartile range, 2 - 9); 22% of patients died during follow-up and only 7 (<1%) required a liver transplant. Among the 2690 alive and without cirrhosis at 6 months post-discharge, 29% were diagnosed with cirrhosis during follow-up. Among women with acute alcoholic hepatitis, 35% had progressed to cirrhosis.

The adjusted risk of progression from acute alcoholic hepatitis to cirrhosis was 47% greater among women than men (sHR, 1.47; 95% CI, 1.23 - 1.76; P <.001). Investigators additionally observed an increased likelihood of older age (sHR, 1.05; 95% CI, 1.03 - 1.06) and higher comorbidity counts (sHR, 1.36; 95% CI, 1.01 - 1.82) among those progressed to cirrhosis.

Cumulative incidence of death at 1, 5 and 10 years increased gradually among patients with cirrhosis, from 9% to 22% then 31%, respectively.

In the second segment of an interview with HCPLive during The Liver Meeting, Flemming discussed the impact of acute alcoholic hepatitis on the young adult population—likening it to a “car crash” that accelerates patients to late-stage burdens of cirrhosis quicker than other liver diseases.

“You don’t necessarily have to have underlying liver disease, but with significant alcohol consumption in the individual who is predisposed, all of sudden that can cause a very significant liver injury and people can develop liver failure even if they don’t have any cirrhosis in the background,” Flemming said.

While Flemming and her colleagues are anecdotally observing a greater rate of younger patients presenting with acute alcoholic hepatitis, there remains a lack of data on long-term outcomes beyond hospitalizations. “If they’re able to survive that car crash, what happens to them 5, 10, 15 years down the road?” she prosed.

Regarding the sex disparity of outcomes, Flemming said the findings validate what she and her peers observe in clinic—a significant uptick in female patients with acute and debilitating alcohol-related liver disease—and further strengthen the call for sex-specific responses to the growing issue of acute alcoholic hepatitis overall.

“We also show there’s differences in their demographics and social determinants of health between the men and women that are suffering from alcoholic hepatitis—they’re just different individuals,” Flemming said.

Regarding applicable solutions to the emerging crisis, Flemming pointed to public health policies surrounding alcohol, as well as general public education campaigns.

“The bias is that alcohol is not affecting women and it’s also not affecting young people, but when you look at data it’s hard to ignore that when you took this group of individuals, the average age was 33, and within 5 years, 25% of them died,” Flemming said. “That should be, I think, thought of as a public health crisis.”