357.1 🎓 醫孞生版

357.1.0.1 📌 䞀頁重點

357.1.0.1.1 Autoimmune Hepatitis (AIH)

357.1.1 Epidemiology

  • F > M (3-4:1)
  • All ages; peaks 10-30 + 40-60
  • Genetic (HLA-DR3, DR4)

357.1.2 Subtypes

Type 1 (Most Common): - ANA + Anti-Smooth Muscle Antibody (ASMA, anti-actin) - Adults + children - Slowly progressive

Type 2: - Anti-LKM-1 (anti-liver-kidney microsome) - Anti-LC1 (anti-liver cytosol-1) - Pediatric (more common in children) - More aggressive

Type 3 (older classification): - Anti-SLA/LP (soluble liver antigen) - Now considered Type 1 variant

357.1.3 Clinical Presentation

  • Asymptomatic (incidental LFT abnormality)
  • Acute presentation (ALT > 1000 sometimes)
  • Chronic presentation (fatigue, jaundice)
  • Cirrhosis (~ 30% at diagnosis)
  • Acute liver failure (rare)
  • Extrahepatic: arthralgia, thyroiditis, T1DM, vitiligo, celiac

357.1.4 Diagnosis

Lab: - ALT/AST elevation - ↑ IgG (specific) - ANA (most common autoantibody) - ASMA / anti-actin - Anti-LKM-1, anti-LC1 (Type 2) - Anti-SLA/LP

Scoring (Diagnostic): - Simplified IAIHG criteria - Composite: ANA/ASMA/LKM titers + IgG + biopsy + viral exclusion

Biopsy (Essential): - Interface hepatitis (lymphocytic infiltrate at portal-parenchymal interface) - Plasma cell infiltrate (often) - Lobular activity - Fibrosis staging

357.1.5 Treatment

Induction: - Prednisone 30-40 mg/d (or 60 mg if severe) - + Azathioprine 1-2 mg/kg (after 1-2 weeks) - Steroid-sparing approach with AZA after week 2

Alternative Initial: - Budesonide + AZA (less systemic steroid side effects) - For non-cirrhotic patients

Maintenance: - AZA monotherapy 1-2 mg/kg - Long-term (years) - 50-70% achieve sustained remission

Refractory Cases: - MMF (mycophenolate mofetil) — increasing use - Tacrolimus - Rituximab - Infliximab (some) - Combination

TPMT Testing: - Before azathioprine - Risk of severe myelosuppression if deficient

357.1.6 Discontinuation

  • After ≥ 2-3 years complete remission
  • Histological remission
  • Trial taper
  • Many relapse → restart

357.1.7 Long-Term Monitoring

  • Periodic LFTs
  • Surveillance for cirrhosis + HCC
  • Vaccinations
357.1.7.0.1 Primary Biliary Cholangitis (PBC)

357.1.8 Epidemiology

  • Female 9:1 (most strongly female-predominant liver disease)
  • 40-60 yo typical onset
  • Often subclinical for years
  • Family clustering (genetic + environmental)

357.1.9 Pathophysiology

  • T-cell mediated destruction of small + medium intrahepatic bile ducts
  • Granulomatous inflammation
  • Progressive cholestasis → cirrhosis

357.1.10 Clinical Presentation

  • Often asymptomatic (incidental ALP elevation)
  • Fatigue (classic, may be severe)
  • Pruritus (cholestasis)
  • Jaundice (later)
  • Xanthomas (cholesterol)
  • Sjögren-like dryness
  • Hepatosplenomegaly
  • Osteoporosis (cholestasis)
  • Eventually cirrhosis with complications

357.1.11 Associated Conditions

  • Sjögren syndrome (most common)
  • Autoimmune thyroid disease
  • Celiac disease
  • Raynaud, scleroderma, CREST
  • Pulmonary fibrosis
  • ITP

357.1.12 Diagnosis

Lab: - ALP + GGT elevated (cholestatic) - ALT, AST less prominent - AMA (anti-mitochondrial antibody, M2 subtype) — 95% positive — highly specific - ANA (50%+) — anti-Sp100, anti-gp210 specific patterns - ↑ IgM (often)

Biopsy (Confirmatory): - Florid duct lesion + granulomas - Bile duct loss - Fibrosis staging (Ludwig 1-4)

357.1.13 Treatment

Ursodeoxycholic Acid (UDCA) — First-Line: - 13-15 mg/kg/d - Lifelong - Slows progression, improves survival - ~ 40% inadequate response

For Inadequate Response (POISE Trial Criteria): - Obeticholic acid (Ocaliva) — FXR agonist (FDA 2016) - 5-10 mg/d - For UDCA-inadequate response - Black box: hepatic decompensation in advanced cirrhosis - Side effects: pruritus (intense), fatigue - Bezafibrate — PPAR-α agonist (off-label, evidence-based) - Fenofibrate — alternative

NEW 2024 — Major Updates: - Elafibranor (Iqirvo) — PPAR α/ÎŽ dual agonist — FDA approval June 2024 for PBC - For inadequate UDCA response - ↓ ALP + improved pruritus - ELATIVE trial - Seladelpar (Livdelzi) — PPAR ÎŽ selective — FDA approval August 2024 for PBC - ↓ ALP + pruritus - RESPONSE trial

Symptom Management: - Pruritus: cholestyramine, rifampin, naltrexone (titrate), gabapentin, sertraline - Fatigue: limited; modafinil tried - Osteoporosis: bisphosphonates - Fat-soluble vitamins (ADEK)

Liver Transplant: - For end-stage - Excellent outcomes - Recurrence in transplanted liver possible (20-30%)

357.1.13.0.1 Primary Sclerosing Cholangitis (PSC)

357.1.14 Epidemiology

  • Male > female (2:1)
  • 30-50 yo typical
  • Strong UC association (75-90% of PSC have IBD)
  • 5% of UC have PSC (more in males)
  • Crohn’s colitis less commonly

357.1.15 Pathophysiology

  • Idiopathic
  • Chronic fibrosing inflammation of intrahepatic + extrahepatic bile ducts
  • “Onion-skin” periductal fibrosis
  • Progressive cirrhosis
  • Increased cholangiocarcinoma (10-15% lifetime risk)
  • Increased gallbladder cancer
  • Increased CRC if concurrent IBD

357.1.16 Clinical Presentation

  • Often asymptomatic (LFT abnormality on screening UC)
  • Fatigue + pruritus
  • Jaundice + cholangitis episodes
  • RUQ pain
  • Hepatomegaly
  • Eventually cirrhosis + portal hypertension

357.1.17 Diagnosis

Lab: - ALP elevated (often markedly) - Bilirubin variable (often elevated late) - ALT/AST elevation - pANCA (60-80%) - No specific autoantibody like PBC

Imaging: - MRCP (gold standard non-invasive): multifocal strictures + dilations = “beading” of bile ducts - ERCP: similar findings; therapeutic for dominant strictures - Liver biopsy: less critical with MRCP advances

357.1.18 Treatment

No Effective Disease-Modifying Therapy: - UDCA standard dose may help (limited evidence) - High-dose UDCA (28-30 mg/kg) — harmful (per UDCA-PSC trial) - Steroids not effective (unlike AIH overlap) - Antibiotics for cholangitis - Vancomycin oral (some pediatric evidence)

Symptomatic + Procedural: - ERCP with stenting / dilation for dominant strictures - Pruritus management - Surveillance for cholangiocarcinoma

Cholangiocarcinoma Surveillance: - Lifelong - Annual MRCP + CA 19-9 - Difficult to diagnose; high mortality

Colon Cancer Surveillance: - For PSC + IBD - Annual colonoscopy - High risk

Liver Transplant: - For end-stage or cholangiocarcinoma (in select centers, transplant with neoadjuvant therapy — Mayo protocol) - Recurrence in transplanted liver possible (30%+)

357.1.18.0.1 Overlap Syndromes

357.1.19 AIH-PBC Overlap

  • Features of both
  • Treat with steroids + UDCA

357.1.20 AIH-PSC Overlap

  • Less common
  • Steroids + UDCA

357.1.21 Sjögren + PBC

  • Common combination
  • Multidisciplinary
357.1.21.0.2 Differential
  • Viral hepatitis (B, C)
  • ALD / MASLD
  • Drug-induced
  • Wilson disease
  • Hemochromatosis
  • Alpha-1 antitrypsin
  • Hereditary cholestasis

357.1.21.1 🩺 床邊速查

  • AIH: F > M; ANA + ASMA + ↑ IgG; interface hepatitis + plasma cells; prednisone + azathioprine
  • PBC: F 9:1; AMA 95% + ALP/GGT elevated; UDCA 13-15 mg/kg lifelong; obeticholic acid, elafibranor + seladelpar FDA 2024 for inadequate
  • PSC: M > F; UC association 75-90%; MRCP “beading”; pANCA; no effective medical therapy except UDCA modest; cholangiocarcinoma risk 10-15%
  • Overlap syndromes: AIH-PBC, AIH-PSC
  • IgG4-related cholangitis: mimics PSC, steroid-responsive
  • Liver transplant for end-stage all three