Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) | | Updated NAFLD/NASH Guidelines

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Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) | USMLE Step 2 CK | Updated NAFLD/NASH Guidelines

his high-yield USMLE Step 2 CK lecture focuses on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) — the newly adopted term replacing Non-Alcoholic Fatty Liver Disease (NAFLD). This update reflects a more precise understanding of the metabolic underpinnings of hepatic steatosis and aligns with international consensus guidelines to better characterize the disease based on metabolic risk factors rather than solely on the absence of alcohol intake. MASLD is now recognized as the most common chronic liver disease in the United States and globally, closely associated with obesity, insulin resistance, type 2 diabetes, dyslipidemia, and metabolic syndrome.

We begin with the pathophysiology of MASLD, emphasizing hepatic fat accumulation due to insulin resistance, leading to lipotoxicity, inflammation, hepatocyte ballooning, and eventually fibrosis. MASLD includes a spectrum ranging from simple steatosis to Metabolic dysfunction–associated steatohepatitis (MASH), formerly known as NASH. Clinical progression may lead to cirrhosis, hepatocellular carcinoma, and increased cardiovascular risk.

Diagnostic workup involves identifying patients with hepatic steatosis on imaging (ultrasound, FibroScan, MRI) or elevated liver enzymes in the setting of metabolic risk factors. The diagnosis of MASLD no longer requires exclusion of alcohol use or other liver diseases, but rather is defined by the presence of hepatic steatosis with at least one metabolic risk feature such as central obesity, high triglycerides, low HDL, hypertension, or elevated fasting glucose. Tools such as the FIB-4 score, NAFLD fibrosis score, and transient elastography help assess fibrosis risk.

Management focuses on lifestyle modification, including weight loss through diet and exercise, which remains the cornerstone of therapy. A sustained weight loss of 7 to 10 percent can reverse steatohepatitis and even improve fibrosis. Pharmacologic treatments such as GLP-1 receptor agonists (e.g., semaglutide) and pioglitazone are under investigation or selectively used in patients with biopsy-proven MASH. Statins are safe and indicated for patients with coexisting dyslipidemia and cardiovascular risk.

This lecture provides the latest terminology, diagnostic criteria, and treatment strategies relevant to Step 2 CK, helping students understand how to identify and manage MASLD in clinical vignettes, especially when evaluating elevated liver enzymes, metabolic syndrome, or incidental findings of hepatic steatosis.


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