Key Clinical Summary: Diagnostic Updates in Metabolic Dysfunction-Associated Steatohepatitis and How to Identify Patients at Risk of Mortality

This is a micro-learning module summary of Prof Arun Sanyal's MASH Academy session which you can find here.

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The MASH Academy was supported by an independent medical education grant from Novo Nordisk.

Introduction:

There is a critical need for improved identification of patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH), a progressive form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), who are at increased risk of mortality. MASLD, driven by the global obesity pandemic, often progresses silently, with many patients unaware of their condition until they develop advanced liver disease or complications. The core objective is to equip clinicians, particularly those in primary care, with the tools to effectively identify individuals at risk of progressing to cirrhosis, enabling timely intervention and improved patient outcomes.

The MASLD Spectrum and the Importance of Fibrosis:

MASLD encompasses a spectrum of liver conditions, starting with steatosis (fatty liver) and potentially progressing to MASH (characterized by inflammation and liver injury), fibrosis (scarring), and ultimately cirrhosis. The following are two key concepts:

Disease Activity: Reflects the ongoing injury to the liver, comprising steatosis, hepatocellular ballooning (a specific type of liver cell injury), and inflammation.
Fibrosis Stage: Indicates the extent of scarring and is the most critical prognostic factor, strongly correlating with the risk of liver decompensation and mortality. Progression to cirrhosis represents a significant milestone, dramatically increasing the risk of adverse outcomes.

Non-Invasive Tests for Risk Stratification:

Non-invasive tests (NITs) are important for identifying patients with advanced fibrosis. Key tools include:

FIB-4 Score: A simple, readily available blood test calculated using age, AST, ALT, and platelet count.
FIB-4 < 1.3 indicates a low risk of advanced fibrosis.
FIB-4 ≥ 1.3 should have VCTE or alternative test
Liver Stiffness Measurement (LSM) by Vibration-Controlled Transient Elastography (VCTE, FibroScan): A non-invasive imaging technique that measures liver stiffness, a surrogate marker for fibrosis.
LSM < 8 kPa is considered low risk.
LSM ≥ 8 kPa should be referred to hepatologist
Enhanced Liver Fibrosis (ELF) Test: A blood test that measures specific markers of fibrosis.
ELF < 9.8 rules out short-term adverse liver outcomes with NPV of 90%
ELF > 11.3 indicates a high risk of adverse liver outcomes

2D Magnetic Resonance Elastography (MRE): An advanced imaging technique that is also useful for prognostic assessment.

Advanced Practitioner Considerations:

For more specialized settings, additional scoring systems:

FAST Score: Designed to identify patients with MASH at high risk
Agile 3+ and Agile 4: Scores designed to improve the identification of advanced fibrosis and cirrhosis.

Portal Hypertension Assessment:

In patients with advanced fibrosis or cirrhosis, assessment for clinically significant portal hypertension (CSPH) is crucial. Non-invasive criteria, such as the Baveno criteria, utilizing liver stiffness and platelet count, can help predict the presence of CSPH.

LSM < 15 kPa and normal platelets can rule out CSPH.
LSM > 25 kPa can rule in CSPH.

MASLD as a Systemic Disease:

MASLD is not solely a liver disease but a component of a multisystem metabolic disorder. Patients with MASLD have an increased risk of:

Cardiovascular disease
Hypertension
Type 2 diabetes
Chronic kidney disease
Certain cancers

Therefore, a holistic approach to risk assessment is essential, considering both liver-related and systemic risks.

Integrated Risk Assessment:

A comprehensive approach to patient evaluation, incorporates:

Liver risk assessment (FIB-4, LSM, ELF)
Cardiovascular risk assessment (ASCVD or AHA PREVENT calculator)
Renal function assessment (eGFR)
Glycemic control assessment (HbA1c)

This integrated approach allows for a more personalized and precise assessment of overall patient risk, guiding management strategies and prioritizing interventions.

Summary:

Effective identification of patients with MASH at risk of progression is critical to improve outcomes. Non-invasive tests play a vital role in risk stratification, allowing clinicians to target interventions appropriately. Recognizing MASLD as a systemic disease and assessing overall patient risk are crucial for comprehensive management.