At the 75th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), metabolic-associated fatty liver disease (MAFLD) garnered significant attention. Dr. Jun Chen from Shenzhen Third People’s Hospital shared insights on key clinical studies that highlight advancements in the diagnosis and prognosis of MAFLD.Study 1: MASEF Scoring System for High-Risk MASH Diagnosis
High-risk MASH, defined as NAFLD activity score (NAS) ≥ 4 and fibrosis stage ≥ 2, is associated with increased liver-related mortality. However, non-invasive diagnostic tools are essential for identifying factors that elevate liver and all-cause mortality risks.
A study led by Dr. Kanagalingam evaluated the diagnostic utility of the MASEF® score, which incorporates 12 lipid markers, BMI, AST, and ALT, in identifying high-risk MASH and its histological components. The diagnostic performance of MASEF® was compared to ALT for MASH and to FIB-4 for fibrosis stages.
- Participants: 1,073 subjects with a mean age of 52.5 years, BMI of 34.8 kg/m², 490 with type 2 diabetes, 835 diagnosed with MASH, and 198 with cirrhosis.
Key Findings:
- MASEF® outperformed ALT in diagnosing MASH and NAS ≥ 4 and surpassed FIB-4 in identifying fibrosis stage ≥ 2.
- However, it showed reduced diagnostic value for advanced fibrosis or cirrhosis.
Conclusion: The MASEF® score is a promising tool for identifying high-risk events in MAFLD populations.
Study 2: T2DM and Glycemic Control’s Role in MAFLD Progression
This multicenter, prospective study investigated the association between type 2 diabetes mellitus (T2DM), glycemic control, and liver stiffness progression in MAFLD patients using vibration-controlled transient elastography (VCTE).
- Participants: 1,231 adults (62% female) with MAFLD, undergoing more than one VCTE scan. Mean age: 51.8 years; mean BMI: 34.0 kg/m².
Findings:
- Over 4, 6, and 8 years, cumulative liver stiffness measurement (LSM) progression rates were significantly higher in T2DM patients compared to non-T2DM patients (P = 0.04).
- Adjusted hazard ratio (HR) for T2DM and LSM progression: 1.35 (95% CI: 1.01–1.81, P = 0.04).
- HbA1c was associated with increased LSM progression (adjusted HR = 1.18, P = 0.003) and decreased likelihood of LSM improvement (adjusted HR = 0.84, P = 0.02).
Conclusion:
T2DM accelerates liver stiffness progression in MAFLD, underscoring the importance of glycemic control in managing disease progression.
Study 3: Polygenic Risk Scores (PRS) for Predicting MAS and Fibrosis Progression
This study evaluated the effectiveness of polygenic risk scores (PRS) in predicting MAFLD activity score (MAS) and advanced fibrosis using histology-validated data.
- Participants: 3,049 biopsy-confirmed MAFLD patients, including GWAS and NASH CRN exome sequencing data.
- PRS Models: Five PRS systems (Chen, Emdin, Whitfield, Schwantes-An, and Vujkovic) incorporating various SNPs were assessed.
Findings:
- PRS-Chen (16 SNPs) strongly correlated with MAS and fibrosis progression.
- PRS-Schwantes-An demonstrated strong associations with fibrosis across continuous and categorical factors.
Conclusion:
The 16-SNP PRS-Chen showed significant predictive value for steatohepatitis and fibrosis progression and could guide future clinical trial designs.
Implications
These studies highlight the growing potential of combining genetic, clinical, and non-invasive diagnostic tools to improve MAFLD diagnosis and prognosis. They also underscore the importance of integrating baseline comorbidities, genetic predispositions, and advanced scoring systems for a comprehensive assessment of disease progression.
Further research and validation are needed to refine these tools and ensure their applicability in diverse clinical settings.
