Alcohol-Associated Liver Disease Conveys Greater Cirrhosis Risk Than Metabolic Disease

Among patients with steatotic liver disease (SLD), patients with alcohol-associated liver disease (ALD) carry the highest risk of cirrhosis, followed by those with metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic- and alcohol-associated liver disease (MetALD), according to a new study.

The report highlights the ways in which alcohol affects cirrhosis risk but also underscores the “synergistic effect” that concurrent metabolic dysfunction and alcohol use can have on cirrhosis risk. The study was published in JHEP Reports.¹

The authors noted that steatotic liver disease has become the most common indication for liver transplantation among US adults with end-stage liver disease. The category of SLD can include people with multiple metabolic comorbidities and no significant alcohol use, as well as patients whose etiology is primarily due to alcohol use, they said. Some patients have liver disease tied to both metabolic dysfunction and alcohol use; such patients fall into the MetALD category, the authors noted.

Still, only a few studies have looked at the long-term risk of cirrhosis among people with MASLD, MetALD, and ALD. Moreover, as the nomenclature surrounding liver disease has evolved, there is a need for new research linking subtypes to prognoses. One such study, a 2024 report in The Lancet Gastroenterology & Hepatology, found that different subclasses of SLD were tied to distinct prognoses, but also found that there is a need for more research into how historical alcohol use should be factored into risk stratification.²

The authors of the current study hypothesized that there is significant reason to suspect that MetALD might “confer a unique risk for cirrhosis” due to the interplay between metabolic dysfunction and alcohol use, although they said such data are limited.¹

In the new report, the investigators decided to study these questions using the Veterans Affairs health system database, which includes data on more than 1 million US military veterans with diagnosed SLD. The database yielded 682,274 veterans with MASLD, 517,464 with MetALD, and 305,692 with ALD. The data covered the years of 2010 through 2023, and the median follow-up was 7.2 years.

The investigators found that people with ALD had the highest incidence of cirrhosis (0.66 cases per 100 person-years). People with MASLD had an incidence of 0.43 cases per 100 person-years, and people with MetALD had an incidence of 0.39 cases per 100 person-years (P < 0.001).

“These findings are consistent with prior literature demonstrating a heightened risk of cirrhosis among individuals with ALD,” they wrote.

Mortality similarly was highest among people with ALD (0.32 per 100 person-years), followed by MASLD (0.24 per 100 person-years) and MetALD (0.19 per 100 person-years).

Patients with MASLD and concurrent obesity and diabetes had a 36% higher risk of cirrhosis, and those with obesity and diabetes as well as MetALD had a 22% increased risk, compared with patients without the 2 conditions.

The authors said it was notable that patients with MetALD had the lowest risk of cirrhosis and death.

“The underlying reasons for this are unclear, but it is important to note that we evaluated outcomes based on index diagnosis,” they wrote. “Alcohol use and progression of or optimization of metabolic comorbidities can change over time.”

The investigators said they also identified notable demographic disparities in cirrhosis risk. They found that Hispanic patients tended to have a higher risk of cirrhosis compared with non-Hispanic White patients, whereas African-American patients had a lower risk. Women also tended to have lower risk.

“These findings may reflect differences in susceptibility, access to care, or lifestyle factors that warrant further investigation,” they said.

The authors suggested that future studies should look more closely at how metabolic and alcohol-related risk factors contribute to cirrhosis risk.

“Furthermore, interventions focused on lifestyle modification, optimization of metabolic comorbidities, and alcohol reduction must be pursued in parallel in an effort to reduce the risk of cirrhosis in this vulnerable veteran population,” they wrote.

References

1. Sedki M, Yang Z, Singal AK, et al. Longitudinal risk of cirrhosis by steatotic liver disease subtype among 1.5 million individuals in the US. JHEP Rep. 2025;8(3):101680. doi:10.1016/j.jhepr.2025.101680
2. Israelsen M, Torp N, Johansen S, et al. Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study. Lancet Gastroenterol Hepatol. 2024;9(3):218-228. doi:10.1016/S2468-1253(23)00443-0