Stigma and Sex Differences in ALD Care, With Frances Lee, MD

Age-adjusted mortality from alcohol-associated liver disease (ALD) nearly doubled nationally, climbing from 6.71 to 12.53 deaths per 100,000 between 1999 and 2022, with a significant acceleration from 2018 to 2022 (annual percentage change, 8.94%; 95% CI, 6.27%-14.51%; P = .001).¹

Of the 436,814 ALD deaths recorded across those 2 decades, women and adults aged 25 to 44 years experienced particularly pronounced increases, even as men accounted for 70.7% of total deaths.¹ Earlier identification remains a challenge, particularly when alcohol use is underreported or not routinely discussed during clinical encounters.

Frances Lee, MD, joined Mount Sinai's REACH Program in April 2025 to integrate hepatology care with addiction treatment.² She now directs Mount Sinai's Alcohol-Associated Liver Disease Program, which uses a harm-reduction model to address the complex needs of patients with alcohol-associated liver disease.²

"Through my co-location within REACH, we've created a destination where patients ... can now get multispecialty, wraparound services," said Lee, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai.²

Biological differences may also contribute to differences in alcohol exposure. Women generally reach higher blood alcohol concentrations than men after consuming equivalent amounts of alcohol, in part because of differences in total body water and body composition.³ A 2025 analysis found that PNPLA3 and TM6SF2 variants were associated with greater fibrosis risk in the setting of both alcohol use and metabolic dysfunction.⁴ The interaction was particularly pronounced among younger patients with metabolic risk and heavier alcohol consumption.⁴

In the following interview with HCPLive, Lee discusses how alcohol-related stigma can affect clinical care and how biological and metabolic factors may contribute to differences in ALD risk and progression among women and younger adults.

Q&A: stigma and biology behind rising ALD rates

HCPLive: What does alcohol-related stigma look like in practice at REACH, and where does it derail a patient's path to treatment?

Frances Lee, MD: Not every patient shares the moments in their lives or their health care experiences in which they felt stigmatized for their alcohol intake. However, we know that the word "alcoholic" comes with stigma, and in using "alcohol-associated liver disease" or "alcohol use disorder," patients may feel that they are seen as more than just their addiction and become open to creating a therapeutic relationship with their health care provider.

HCPLive: Is there a suspected but underexplored biological mechanism behind faster ALD progression in younger adults and women, and how could it be studied?

Frances Lee, MD: The biological basis of ALD in women, and why ALD may progress faster in women, has been studied in the past. We know women are generally smaller and have decreased total body water and higher body fat percentage, which causes higher blood alcohol concentrations compared with men who ingest the same amount of alcohol. This makes sense, as we know alcohol causes dose-dependent injury to the liver.

There is still so much to learn, though, about other features of sex differences, such as hormone levels and menopausal status, and their effect on the progression of ALD. We additionally acknowledge that metabolic factors and alcohol intake combined act like adding fuel to the fire, and with the increasing incidence of diabetes, obesity, and other features of metabolic syndrome, especially in younger patients, the more likely we are to see clinical disease. We are also increasingly aware of genetic factors that may increase one's risk of developing liver disease, whether from PNPLA3 polymorphisms or otherwise.

These genetic polymorphisms may help elucidate why younger patients are developing liver disease, especially alongside the progression of metabolic disease and alcohol intake.

HCPLive: What single shift in screening, clinical mindset, or the evidence base would make the biggest difference for this patient population?

Frances Lee, MD: More evidence is needed to inform how providers counsel patients.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Lee does not report any relevant disclosures.

References

1. Mount Sinai Health System. Mount Sinai helps set a new standard for treating alcohol-associated liver disease. Published 2026. Accessed September 21, 2026. https://reports.mountsinai.org/article/liver2026-reach-clinic-for-alcohol-related-liver-disease

2. Pan CW, Abboud Y, Chitnis A, Zhang W, Singal AK, Wong RJ. Alcohol-associated liver disease mortality. JAMA Netw Open. 2025;8(6):e2514857. doi:10.1001/jamanetworkopen.2025.14857

3. Kezer CA, Simonetto DA, Shah VH. Sex differences in alcohol consumption and alcohol-associated liver disease. Mayo Clin Proc. 2021;96(4):1006-1016. doi:10.1016/j.mayocp.2020.08.020