Liver Part 2: ALD, MASLD/MASH, Cholestatic Disease, and Hepatic Encephalopathy
Corticosteroids in alcoholic hepatitis · MASH pharmacotherapy · UDCA and obeticholic acid · Lactulose and rifaximin
Alcoholic Liver Disease: Severity Scoring and Treatment
Maddrey Discriminant Function
Treatment Threshold ≥32
  • Formula: 4.6 × (PT − control PT) + bilirubin μmol/L ÷ 17.1
  • Score ≥32: severe; 28-day mortality >30% without treatment
  • Score ≥32: consider prednisolone if no contraindications
  • Score below 32: supportive care, abstinence; no corticosteroids
Prednisolone Treatment
40 mg Daily × 28 Days
  • Reduces 28-day mortality in severe alcoholic hepatitis
  • Exclude active infection and HBV before starting
  • Assess Lille score at day 7: score >0.45 = non-responder
  • Non-responder: stop prednisolone; evaluate for transplant
  • Pentoxifylline: no longer recommended (STOPAH trial: no survival benefit)
MASLD/MASH: Treatment Hierarchy
First Line
Lifestyle Modification
  • 7–10% weight loss: histological improvement in majority
  • >10% weight loss: fibrosis regression in many
  • Most effective intervention available
First Approved MASH Drug (2024)
Resmetirom
  • Thyroid hormone receptor-beta agonist (liver-targeted)
  • Stimulates hepatic fatty acid oxidation; reduces triglycerides
  • No cardiac effects (THR-beta spares heart)
  • Approved: non-cirrhotic MASH with fibrosis stage F2–F3
  • MAESTRO-MASH trial: superior MASH resolution vs. placebo
Selected Patients
Vitamin E and Pioglitazone
  • Vitamin E 800 IU daily: non-diabetic MASH; improves steatosis/inflammation; not fibrosis
  • Pioglitazone: MASH with type 2 diabetes; PPAR-gamma agonist; improves insulin sensitivity
  • GLP-1 agonists (semaglutide): improving evidence in MASH; not yet liver-specific indication
Primary Biliary Cholangitis: Sequential Treatment
Agent Mechanism Indication Key Caution
UDCA 13–15 mg/kg/day Replaces toxic bile acids; stimulates bile export; membrane stabilization First-line for all PBC patients 30–40% have inadequate response at 12 months
Obeticholic acid FXR agonist: reduces bile acid synthesis (suppresses CYP7A1) Add-on for inadequate UDCA response Pruritus (majority); contraindicated in decompensated cirrhosis
Bezafibrate PPAR-alpha agonist: modulates bile acid metabolism Alternative add-on; better tolerated pruritus profile Off-label; monitor renal function and creatine kinase
Hepatic Encephalopathy: Treatment and Secondary Prophylaxis
Lactulose (Acute + Maintenance)
Trap Ammonia as NH4+ in Colon
  • Fermented by bacteria → lowers colonic pH → NH3 → NH4+ (trapped)
  • Target: 2–3 soft stools per day
  • Over-purging: dehydration, hyponatremia → worsens encephalopathy
  • First step: always identify and correct precipitant (bleeding, infection, constipation, hypokalemia, sedatives)
Rifaximin (Secondary Prophylaxis)
Add to Lactulose After First Episode
  • 550 mg twice daily + lactulose: reduces recurrence by 58%
  • Reduces hospitalization for HE by 50%
  • Minimally absorbed (<0.4%): intraluminal action; well tolerated
  • Indicated after first HE episode for secondary prophylaxis
  • Do NOT restrict protein: maintain 1.2–1.5 g/kg/day
Key Rule — Alcoholic Hepatitis

Exclude active infection and HBV co-infection before starting prednisolone. Assess Lille score at day 7. Pentoxifylline is no longer recommended. Abstinence from alcohol is the most important long-term determinant of survival.