Liver and Bile
Lancet Gastroenterol Hepatol. 2024;9(3):218–28
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
Background: Steatotic liver disease is a new overarching term that includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD). The authors aimed to validate the prognostic importance of MASLD, MetALD, and ALD as steatotic liver disease subclasses.
Methods: Between April 18, 2013, and September 17, 2018, they prospectively recruited patients aged 18–75 years with current or previous excessive alcohol intake (> 24 g/day for women and > 36 g/day for men) for at least a year and no previous hepatic decompensation from the Department of Gastroenterology and Hepatology at Odense University Hospital (Denmark). Participants were followed up until September 15, 2022. Here, the authors characterize these patients according to steatotic liver disease subclasses. They classified patients as having MASLD, MetALD, or ALD in accordance with the nomenclature definitions, on the basis of metabolic comorbidity and self-reported average alcohol intake in the 3 months leading up to inclusion. Histological scoring was done by a pathologist who was masked to the clinical data. Prognoses between classes were compared using Cox regression analyses on hepatic decompensation and overall mortality as the 2 outcome measures. Patients not meeting the criteria for steatotic liver disease were classified as no steatotic liver disease and served as a reference group.
Findings: 446 patients with a history of excessive alcohol intake were enrolled in this analysis (334 [75%] were male and 112 [25%] were female; median age 56 years [standard deviation 10]). Cirrhosis was present in 58 (13%), and 435 (98%) had at least 1 cardiometabolic risk factor. 321 (72%) met steatotic liver disease criteria and 125 (28%) did not have steatotic liver disease, meaning no evident liver steatosis and no significant fibrosis (≥ F2). Of the 321 patients with steatotic liver disease, 6 (2%) were identified as having ALD due to the absence of cardiometabolic risk factors. The remaining 315 patients (98%) presented with at least 1 cardiometabolic risk factor. Of these patients, 153 (49%) had MASLD, 76 (24%) had MetALD, and 86 (27%) had ALD. During follow-up, 67 of 446 patients (15%) decompensated and 97 (22%) died (median follow-up 70 months [interquartile range, 53–94]). Patients with steatotic liver disease had a significantly higher risk of hepatic decompensation and overall mortality than those without steatotic liver disease, independent of age, sex, and liver stiffness. The risk of decompensation increased in a stepwise manner from MASLD (hazard ratio [HR] = 4.73; 95% confidence interval [CI]: 1.03–21.6), through MetALD (HR = 7.69; 95% CI: 1.66–35.6), to ALD (HR = 10.2; 95% CI: 2.24–46.4). Similarly, overall mortality increased from MASLD (HR = 2.30; 95% CI: 1.08–4.90), through MetALD (HR = 2.94; 95% CI: 1.31–6.58), to ALD (HR = 3.57;95% CI: 1.64–7.80), independent of age, sex, and liver stiffness.
Interpretation: Steatotic liver disease and its subclasses portend distinct prognoses. There is a need to specify how historical alcohol intake should be integrated into the nomenclature and risk stratification of steatotic liver disease.