Improving Fibrosis Risk Stratification in MetALD, with Brian Lee, MD

In 2023, A modified Delphi process led by the American Association for the Study of Liver Disease, the European Association for the Study of the Liver, and the Latin American Association for the Study of the Liver yielded new liver disease nomenclature to address concerns regarding the terminology “nonalcoholic fatty liver disease” and “metabolic-associated fatty liver disease.”

The revised nomenclature introduced the term “metabolic dysfunction-associated steatotic liver disease” (MASLD) to describe patients who have hepatic steatosis and ≥ 1 of 5 cardiometabolic risk factors (CRMF). Additionally, the updated nomenclature added a new classification, MetALD, to represent a separate group of patients with MASLD who consume alcohol at a rate of 140–350 g/wk for females and 210–420 g/wk for males.2

“There have been several questions that have come up because of the nomenclature, but one of the controversies was whether MetALD should be defined by just 1 metabolic risk factor, Brian Lee, MD, a hepatologist and liver transplant specialist with Keck Medicine of USC, explained to HCPLive. “We know that alcohol can actually cause metabolic risk factors. So if you have just 1 and increased alcohol intake, is it truly a distinct disease?”

Lee noted this was one of several questions he and a group of colleagues sought to answer in their recent analysis of NHANES data assessing FIB-4 scores in adults ≥ 20 years of age with complete alcohol and CMRF status.2

Results showed the prevalence of FIB-4 >2.67 among individuals with and without increased alcohol use was higher at each quantity of CMRFs and with each incremental CMRF:

• 0 CRMFs: (2.3%; 95% CI, 1.0-5.0% vs 0.7%; 95% CI, 0.5-0.9%)
• 1 CRMF: (3.0%; 95% CI, 1.6-5.6% vs 1.7%; 95% CI, 1.4-2.1%)
• 2 CRMFs: (3.3%; 95% CI, 2.1-5.1% vs 2.1%; 95% CI, 1.8-2.4%)
• 3 CRMFs: (5.9%; 95% CI, 3.5-9.6% vs 2.5%; 95% CI, 2.1-2.9%)
• 4 or 5 CRMFs (6.1%; 95% CI, 3.3-9.7% vs 4.0%; 95% CI, 3.5-4.5%)

Among individuals with increased alcohol, in multivariable logistic regression analysis, 3 (adjusted odds ratio [aOR], 2.57; 95% CI, 0.93-7.08) and 4 or 5 (aOR, 2.64; 95% CI, 1.05-6.67) CMRFs were associated with 2-fold greater odds of high FIB-4 versus 0 CRMFs, but not 1 (aOR, 1.24; 95% CI, 0.41-3.69) or 2 (aOR, 1.39; 95% CI, 0.56-3.50) CMRFs.2

“The cutoff where you have a different risk of liver fibrosis is not with 1 cardiometabolic risk factor, but it's really with 3 or more,” Lee said. “So, the take-home message here is that we should be classifying MetALD with not just 1, but really 3 or more cardiometabolic risk factors, and maybe having this higher threshold for cut-off would better differentiate the patient populations in steatotic liver disease.”

Editors’ note: Lee has no relevant disclosures.

References

1. Brooks A. From NAFLD to MASLD: 2023 Brings New Liver Disease Nomenclature. HCPLive. December 13, 2023. Accessed February 13, 2025. https://www.hcplive.com/view/from-nafld-to-masld-2023-new-liver-disease-nomenclature

2. Lee BP, Molina J, Kim S, et al. Association of Alcohol and Incremental Cardiometabolic Risk Factors with Liver Disease: A National Cross-Sectional Study. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2025.01.003