357.3 🏥 內科專科考前版

357.3.1 Mechanistic Deep Dive

357.3.1.1 AIH Pathogenesis

  • Loss of self-tolerance
  • T-cell mediated hepatocyte injury
  • HLA-DR3, DR4 association
  • Triggers: drugs (nitrofurantoin, minocycline, ICI), viruses (Hep A, EBV)

357.3.1.2 PBC Pathogenesis

  • T-cell mediated bile duct destruction
  • Mitochondrial pyruvate dehydrogenase E2 (PDC-E2) — autoantigen
  • Granulomatous inflammation
  • Eventually fibrosis

357.3.1.3 PSC Pathogenesis

  • Idiopathic
  • Possible role of gut microbiome (IBD link)
  • Genetic susceptibility
  • Chronic inflammation → fibrosis

357.3.2 Recent Trials & Updates

357.3.2.1 ELATIVE (2024) — Elafibranor PBC

  • PPAR α/ÎŽ dual agonist
  • ↓ ALP + improved pruritus
  • FDA approval June 2024

357.3.2.2 RESPONSE (2024) — Seladelpar PBC

  • PPAR ÎŽ selective
  • ↓ ALP + improved pruritus
  • FDA approval August 2024

357.3.2.3 POISE — Obeticholic Acid

  • FXR agonist
  • For UDCA-inadequate PBC
  • FDA 2016
  • Black box: decompensation in advanced cirrhosis

357.3.2.4 Bezafibrate / Fenofibrate

  • Off-label
  • Evidence in BEZURSO trial
  • Combine with UDCA

357.3.2.5 Anti-Drug Antibody Cholangitis

  • ICI-related PSC-like
  • Increasing recognition

357.3.3 High-Yield Specialist Points

357.3.3.1 AIH Acute Severe / Fulminant

  • Steroid response variable
  • Liver transplant
  • Some require urgent

357.3.3.2 AIH Histological Remission

  • Important goal
  • Not just biochemical
  • Influences treatment duration

357.3.3.3 PBC + Sjögren

  • Very common overlap
  • Multidisciplinary
  • Symptom management

357.3.3.4 PSC + UC + CRC

  • High risk
  • Annual colonoscopy
  • Surveillance from PSC diagnosis

357.3.3.5 PSC + Cholangiocarcinoma

  • 10-15% lifetime risk
  • Difficult diagnosis (background biliary changes)
  • CA 19-9 (false positive with cholangitis common)
  • Cytology + brushings
  • FISH (UroVysion)
  • Liver transplant in select with Mayo protocol (neoadjuvant chemoradiation)

357.3.3.6 Liver Transplant Outcomes

  • PBC: excellent (recurrence 20-30%, generally mild)
  • PSC: recurrence 30%+ (severe)
  • AIH: recurrence common; steroid management

357.3.3.7 Cholangiocarcinoma Treatment

  • Resectable: surgery + adjuvant chemo
  • Locally advanced: chemoradiation
  • Metastatic: chemotherapy (cisplatin + gemcitabine + durvalumab — TOPAZ-1 2022)
  • FGFR2 inhibitors (pemigatinib, futibatinib) for FGFR2 fusion+
  • IDH1 inhibitors (ivosidenib) for IDH1-mutant
  • HER2-targeted for HER2+

357.3.3.9 Pregnancy + Autoimmune Liver

  • Generally improves in pregnancy
  • Flares post-partum
  • Adjust IS (azathioprine OK, MMF teratogenic, MTX teratogenic)
  • Multidisciplinary

357.3.3.10 Pediatric AIH

  • Type 2 more common
  • More aggressive course
  • Same treatment principles
  • Liver transplant outcomes good

357.3.3.11 Acute Cholangitis in PSC

  • Antibiotic coverage
  • ERCP for obstruction
  • Multidisciplinary
  • High mortality if severe

357.3.4 Pearls

  • AIH: ANA + ASMA + ↑ IgG + interface hepatitis + plasma cells; prednisone + azathioprine
  • PBC: AMA 95% + ALP/GGT cholestatic; UDCA + obeticholic / elafibranor / seladelpar
  • PSC: UC association 75-90% + MRCP “beading” + pANCA; cholangiocarcinoma 10-15%; no medical therapy
  • Liver transplant for end-stage all three
  • Cholangiocarcinoma surveillance in PSC (MRCP + CA 19-9)
  • Mayo protocol transplant for hilar cholangiocarcinoma
  • Elafibranor + seladelpar FDA 2024 PBC paradigm shift