Noninvasive Evaluation of Hepatic Steatosis, Inflammation, and Fibrosis

Noninvasive Evaluation of Hepatic Steatosis, Inflammation, and Fibrosis

Summary of Lecture by Prof. Vincent Wong, Chinese University of Hong Kong

1. Main Clinical Topics Discussed

• Reclassification and epidemiology of steatotic liver disease (SLD), including Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and alcohol-associated liver disease (ALD)
• Rationale for noninvasive testing (NIT) to assess hepatic steatosis, inflammation, and fibrosis
• Limitations of liver biopsy as a diagnostic gold standard
• Categories of NITs and their clinical applications
• Specific noninvasive modalities: ultrasonography, Fatty Liver Index (FLI), and Vibration-Controlled Transient Elastography (VCTE/FibroScan) including Controlled Attenuation Parameter (CAP)

2. Key Learning Points, Guidelines, and Recommendations

Disease Classification (per updated nomenclature):

• "Steatotic liver disease" (SLD) is now the overarching umbrella term
• NAFLD is replaced by MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease)
• MASH (Metabolic dysfunction-Associated Steatohepatitis) denotes active inflammation and tissue injury (~20–30% of MASLD patients)
• A new category — MetALD — captures patients with both metabolic risk factors and significant alcohol intake
• MASLD diagnosis requires hepatic steatosis plus at least one of five cardiometabolic risk factors

Rationale for Assessing Each Histological Feature:

• Steatosis: Establishes the diagnosis of SLD; reflects treatment response
• Inflammation: Indicates active disease progression; key criterion for clinical trial enrollment; reflects treatment response
• Fibrosis: Most prognostic histological factor; associated with cirrhosis, decompensation, and HCC; critical for trial eligibility and treatment monitoring

NIT Classification Framework (per FDA/NIH Biomarker Working Group):

• Diagnostic biomarkers – cross-sectional assessment of steatosis, inflammation, fibrosis, cirrhosis, portal hypertension
• Prognostic biomarkers – predict future outcomes (cirrhosis onset, portal hypertension, liver-related events)
• Monitoring biomarkers – serial assessment of disease progression or improvement over time
• Pharmacodynamic/response biomarkers – detect histological change during active treatment (lifestyle or pharmacological)
• Predictive biomarkers – determine likelihood of response to a specific therapy

3. Specific Clinical Data, Statistics, and Study Results

• MASLD Prevalence: A systematic review and meta-analysis (Younossi et al.) reports that >30% of the global general population has MASLD; prevalence is ≥25% across most regions, with lower rates only in Africa
• Liver Transplantation Trends: MASLD was the only liver disease with a continuously rising trajectory as a cause of end-stage liver disease requiring liver transplantation from 2002–2018
• Liver Biopsy Sampling Error (Merriman et al.): Paired biopsies from right and left hepatic lobes during bariatric surgery demonstrated:

- Steatosis agreement (kappa): ~88% — acceptable

- Fibrosis agreement: poor (kappa not specified but described as "abysmal")

- Hepatocyte ballooning (a defining MASH feature): kappa of only ~20%, meaning discordance in >50% of paired samples

• NIT Readiness: Diagnostic and prognostic NIT data are robust; monitoring, response prediction, and predictive biomarker applications remain "work in progress"

4. Practical Takeaways for Clinicians

• Adopt updated SLD nomenclature (MASLD, MASH, MetALD) in clinical documentation and communication, as this reflects the current international guidelines (AASLD, AGA, EASL, APASL)
• Do not rely solely on liver biopsy as a gold standard — sampling error is substantial, particularly for fi