Non Alcoholic Fatty Liver Disease MASLD and MASH

Related Subjects: | Chronic Liver Disease | Cirrhosis | Alkaline Phosphatase (ALP) | Liver Function Tests | Ascites Assessment and Management | Budd-Chiari Syndrome | Autoimmune Hepatitis | Primary Biliary Cirrhosis | Primary Sclerosing Cholangitis | Wilson Disease | Hereditary Haemochromatosis | Alpha-1 Antitrypsin (AAT) Deficiency | Nonalcoholic Steatohepatitis (NASH) | Spontaneous Bacterial Peritonitis | Alcoholism and Alcoholic Liver Disease | Liver Transplantation

🌍 About

• 🧈 MASLD (formerly NAFLD) = fatty liver driven by metabolic dysfunction (obesity, T2DM, dyslipidaemia, HTN), rather than alcohol.
• 🔥 MASH (formerly NASH) = MASLD plus hepatocyte injury + inflammation, often with fibrosis → higher risk of progression.
• Natural history: simple steatosis (MASLD) → MASH → fibrosis → cirrhosis → HCC (risk rises sharply once fibrosis is established).
• ⚡ Pathophysiology (multiple hits): insulin resistance → ↑ hepatic fat (FFA influx + de novo lipogenesis) → lipotoxicity/oxidative stress → inflammatory signalling → stellate cell activation → fibrosis.
• Histology can resemble alcoholic liver disease, but occurs in minimal/no alcohol intake (interpret alcohol carefully and document).

🧬 Aetiology

• 🚨 Metabolic risks: central obesity, T2DM/insulin resistance, dyslipidaemia, hypertension, metabolic syndrome.
• 🧬 Genetics: PNPLA3, TM6SF2 variants increase susceptibility and fibrosis risk.
• 💊 Secondary causes / contributors: corticosteroids, tamoxifen, amiodarone, rapid weight loss, starvation/malnutrition (and consider endocrine causes such as hypothyroidism where relevant).

📊 Comparison: MASLD vs MASH vs Alcohol-Related Liver Disease

🩺 Clinical Features

• Most patients are asymptomatic 💤 and detected via incidental fatty liver on imaging or mild transaminitis.
• Non-specific: fatigue, malaise, RUQ discomfort.
• Advanced disease: jaundice, ascites, variceal bleeding, splenomegaly, sarcopenia.
• Key concept: fibrosis stage (not ALT level) best predicts liver outcomes.

🧪 Investigations

• 📉 LFTs: ALT often > AST early; pattern may flip with advanced fibrosis—don’t rely on ratios alone.
• 📏 Fibrosis risk stratification (UK): use non-invasive scores (e.g., FIB-4) then second-line testing (e.g., ELF or FibroScan) to identify significant fibrosis.
• 📸 Imaging: USS/CT/MRI detect steatosis but cannot reliably distinguish MASLD vs MASH.
• 🔬 Biopsy: gold standard for diagnosing MASH and staging fibrosis when non-invasive tests are discordant or high-stakes decisions depend on histology.
• ❌ Exclude alternatives: viral hepatitis, autoimmune hepatitis, haemochromatosis, Wilson’s (young), coeliac (selected), and alcohol-related liver disease.

💊 Management

• 🏃 Lifestyle (first-line): sustained weight loss (often 7–10%) + regular exercise improves steatosis and can improve inflammation/fibrosis; Mediterranean-style diet 🥗 is practical and cardioprotective.
• 🫀 Treat comorbidities: optimise diabetes, BP and lipids—CVD is the leading cause of mortality.
• 💊 Medicines (specialist-led/selected patients): consider agents that improve metabolic risk and liver outcomes (e.g., pioglitazone in selected diabetics; GLP-1RA/SGLT2i primarily for diabetes/weight with potential liver benefit). Statins are generally safe and important for CVD risk reduction.
• 🧵 Transplant/HCC pathways: for decompensated cirrhosis or HCC; ensure surveillance where indicated.

📉 Prognosis

• MASLD (steatosis only): often stable, especially with improved metabolic control.
• MASH: higher risk of progressive fibrosis → cirrhosis → HCC; fibrosis stage drives prognosis.
• ⚠️ Overall mortality is commonly from cardiovascular disease rather than liver failure.

📚 Teaching Pearl

🧠 In metabolic liver disease, the key question isn’t “Is the ALT raised?” but “Is there significant fibrosis?” Use FIB-4/ELF/FibroScan to risk-stratify, and treat cardiometabolic risk aggressively.