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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
Open accessAbstract
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). We aimed to validate the prognostic importance of MASLD, MetALD, and ALD as steatotic liver disease subclasses.Methods Between April 18, 2013, and Sept 17, 2018, we 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 (Odense, Denmark). Participants were followed up until Sept 15, 2022. Here, we characterise these patients according to steatotic liver disease subclasses. We 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. We compared prognoses between classes using Cox regression analyses on hepatic decompensation and overall mortality as the two 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 We enrolled 446 patients with a history of excessive alcohol intake were included in this analysis (334 [75%] were male and 112 [25%] were female; median age 56 years [SD 10]). Cirrhosis was present in 58 (13%), and 435 (98%) had at least one 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, six (2%) were identified as having ALD due to the absence of cardiometabolic risk factors. The remaining 315 (98%) patients presented with at least one cardiometabolic risk factor. Of these patients, 153 (49%) had MASLD, 76 (24%) had MetALD, and 86 (27%) had ALD. During follow-up, 67 (15%) of 446 patients decompensated and 97 (22%) died (median follow-up 70 months [IQR 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 4·73 [95% CI 1·03-21·6]), through MetALD (7·69 [1·66-35·6]), to ALD (10·2 [2·24-46·4]). Similarly, overall mortality increased from MASLD (HR 2·30 [95% CI 1·08-4·90]), through MetALD (2·94 [1·31-6·58]), to ALD (3·57 [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.Funding EU Horizon 2020 Research and Innovation Program.
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“Notably, MASLD may accelerate the progression of liver disease in individuals with ALD and chronic hepatitis B, and synergistically induce cirrhosis or HCC development. 8,10,11”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [8]
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“Importantly, despite sharing the same prevalence of cardiometabolic risk factors, MetALD is associated with a higher risk of all-cause mortality, underpinning MetALD as a distinct subclass of SLD with poorer prognosis. 8”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [8]
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Metadata
- Authors
- Israelsen, M., Torp, N., Johansen, S., Hansen, C. D., Hansen, E. D., Thorhauge, K., Hansen, J. K., Villesen, I., Bech, K., Wernberg, C., Andersen, P., Lindvig, K. P., Tsochatzis, E. A., Thiele, M., Rinella, M. E., & Krag, A.
- Affiliations
- University of Southern Denmark (DK)
- Odense University Hospital (DK)
- University of Chicago (US)
- Corresponding author
- Krag, Aleksander
- ORCID
- Venue
- The Lancet Gastroenterology & Hepatology
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 9
- Issue
- 3
- Pages
- 218-228
- ISSN
- 2468-1156 (ISSN-L)
- 2468-1253
- OpenAlex
- W4390748462
- Cited by
- 174
- References
- 28
- Citations by year
- 2026: 50 · 2025: 77 · 2024: 46
- FWCI
- 52.79
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- The Lancet. Gastroenterology & hepatology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Horizon 2020 (668031)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- steatotic liver disease, non-alcoholic fatty liver disease, MetALD, alcoholic liver disease, excessive alcohol intake, cardiometabolic risk factors, hepatic decompensation, all-cause mortality, liver fibrosis, liver histopathology, prognosis, liver cirrhosis, metabolic comorbidities, hepatic steatosis, nonalcoholic steatohepatitis, non-alcoholic liver disease
- MeSH terms
- Alcohol Drinking, Fatty Liver, Female, Gastroenterology, Humans, Liver Cirrhosis, Male, Middle Aged, Prospective Studies
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