A new study suggests that steatotic liver disease subtypes are interconnected and should be monitored as evolving trajectories.
Researchers from Charité – Universitätsmedizin Berlin are calling for a shift in how steatotic liver disease (SLD) is classified, arguing that current categories should be viewed as dynamic trajectories rather than static labels.
The study, published in eGastroenterology, suggests that metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD) are not isolated conditions. Instead, they represent a continuum where patients frequently move between classifications based on fluctuating metabolic factors and alcohol use.
The current SLD framework relies on snapshot assessments, but Lanlan Chen, Paul Horn, and Frank Tacke argue that both alcohol exposure and metabolic status change over time. Data from prospective cohorts cited in the study show that 36% of patients initially classified with MetALD shifted to MASLD or ALD within six months. Additionally, 32% of patients with ALD transitioned toward MetALD or MASLD, and 11% of those with MASLD were reclassified.
Mechanistically, the researchers note that alcohol exposure and metabolic dysfunction share pathogenic pathways, including inflammation, oxidative stress, and fibrosis progression. Alcohol consumption can worsen hypertension, obesity, and hypertriglyceridemia, while metabolic dysfunction may make the liver more susceptible to injury from alcohol.
Objective Alcohol Monitoring
A significant challenge in clinical practice is the accuracy of assessing alcohol intake. The authors note that self-reported consumption may underestimate actual intake by as much as 57.7%, which creates uncertainty in diagnosis and risk assessment.
To improve accuracy, the study highlights the role of objective biomarkers, specifically phosphatidylethanol (PEth). This blood-based biomarker reflects alcohol consumption over the preceding one to three weeks. Unlike traditional questionnaires, PEth is less influenced by body mass index or sex.
Expert recommendations suggest that PEth levels below 20 ng/mL generally exclude significant alcohol intake, while levels above 200 ng/mL indicate harmful drinking.
Risk Stratification and Clinical Management
The proposed framework emphasizes longitudinal reassessment rather than assigning a single diagnostic label. This approach integrates metabolic risk factors, alcohol exposure, and fibrosis staging.
The study prioritizes non-invasive tests for fibrosis risk stratification, such as the fibrosis-4 (FIB-4) index and vibration-controlled transient elastography. Fibrosis is a primary determinant of long-term outcomes in patients with liver disease.
These findings may also impact clinical trial design. Because patient classifications can shift, future trials may require repeated monitoring of metabolic status and alcohol exposure to ensure accurate stratification. This is particularly relevant as new treatments, such as thyroid hormone receptor-beta agonists and GLP-1 receptor agonists, enter clinical practice for the treatment of steatotic liver disease.
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