357.4 ð ç« æ«éèš Summary
357.4.1 ð äžå¥è©±çžœçµ
Autoimmune liver diseases äžå€§ïŒ(1) AIH (autoimmune hepatitis) â chronic hepatocellular inflammation, female predominance F 3-4:1, all ages; subtypes Type 1 (ANA + ASMA, most common all ages), Type 2 (anti-LKM-1, anti-LC1, pediatric), Type 3 (anti-SLA/LP, variant); diagnosis â IgG + autoantibodies + biopsy showing interface hepatitis + plasma cell infiltrate; treatment prednisone 30-40 mg/d + azathioprine 1-2 mg/kg standard (TPMT testing pre-AZA); budesonide + AZA non-cirrhotic alternative; MMF/tacrolimus/rituximab refractory; (2) PBC (primary biliary cholangitis, formerly cirrhosis) â female 9:1 (most female-predominant), 40-60 yo onset, AMA 95% (anti-mitochondrial M2 subtype highly specific), chronic destructive cholangitis of small/medium intrahepatic bile ducts; clinical fatigue + pruritus + xanthomas + osteoporosis + Sjögren association; treatment ursodeoxycholic acid (UDCA) 13-15 mg/kg lifelong first-line + for inadequate response: obeticholic acid (Ocaliva, FXR agonist, FDA 2016) + bezafibrate/fenofibrate (off-label) + NEW 2024 elafibranor (Iqirvo, PPAR α/ÎŽ dual agonist, FDA June 2024) + seladelpar (Livdelzi, PPAR ÎŽ selective, FDA August 2024); (3) PSC (primary sclerosing cholangitis) â chronic fibrosing inflammation of intrahepatic + extrahepatic bile ducts, male predominance 2:1, UC association 75-90% (5% of UC have PSC), MRCP gold standard with âbeadingâ multifocal strictures + dilations, pANCA (60-80%), âonion-skinâ periductal fibrosis on biopsy; cholangiocarcinoma risk 10-15% lifetime + gallbladder cancer + CRC if concurrent IBD; no effective medical therapy (UDCA modest at standard dose; high-dose harmful per UDCA-PSC trial; steroids not effective); ERCP for dominant strictures + cholangiocarcinoma surveillance (annual MRCP + CA 19-9) + CRC surveillance (annual colonoscopy if IBD) + liver transplant for end-stage; Mayo protocol transplant for hilar cholangiocarcinoma (select centers, neoadjuvant chemoradiation); overlap syndromes AIH-PBC + AIH-PSC; IgG4-related sclerosing cholangitis mimics PSC, steroid-responsiveã
357.4.2 ð æ²»ç粟èŠ
- AIH inductionïŒprednisone 30-40 mg/d (60 mg severe) + azathioprine 1-2 mg/kg (after 1-2 weeks; TPMT testing pre-treatment); budesonide + AZA non-cirrhotic alternative
- AIH maintenanceïŒAZA monotherapy 1-2 mg/kg long-term; consider discontinuation after ⥠2-3 years complete remission
- AIH refractoryïŒMMF (mycophenolate mofetil), tacrolimus, rituximab, infliximab, combinations
- PBC first-lineïŒUDCA 13-15 mg/kg/d lifelong + monitor ALP response
- PBC UDCA-inadequate (POISE criteria)ïŒobeticholic acid 5-10 mg/d (FXR agonist FDA 2016) OR elafibranor (Iqirvo, PPAR α/ÎŽ FDA June 2024) OR seladelpar (Livdelzi, PPAR ÎŽ FDA August 2024) OR bezafibrate/fenofibrate (off-label)
- PBC pruritusïŒcholestyramine first â rifampin â naltrexone â gabapentin â sertraline â refractory (UVB, plasmapheresis, transplant)
- PSC no effective medical therapyïŒstandard-dose UDCA modest (donât use high-dose harmful); ERCP for dominant strictures; cholangiocarcinoma surveillance (annual MRCP + CA 19-9); CRC surveillance if IBD; transplant for end-stage
- PSC + hilar cholangiocarcinomaïŒMayo protocol (neoadjuvant chemoradiation + transplant) in select centers
- liver transplant for end-stage all three; recurrence common in PSC (30%+) > PBC (20-30%) > AIH
357.4.3 ð¯ ç§é«åž«çèåæé
- AIH classical diagnosisïŒâ IgG + ANA + ASMA + biopsy interface hepatitis + plasma cell infiltrate; Type 1 (most common, all ages, ANA + ASMA), Type 2 (pediatric, anti-LKM-1 + anti-LC1)
- AIH treatment: prednisone 30-40 mg/d + azathioprine 1-2 mg/kg standard; budesonide + AZA non-cirrhotic alternative; TPMT testing before AZA (myelosuppression risk if deficient)
- PBC female predominance 9:1 (most female-predominant liver disease); AMA 95% positive (anti-mitochondrial M2 subtype highly specific); cholestatic LFT pattern; classic symptoms fatigue + pruritus + xanthomas + osteoporosis
- PBC treatment paradigm 2024 update: UDCA 13-15 mg/kg/d lifelong first-line + for inadequate response obeticholic acid (Ocaliva FXR agonist FDA 2016) + elafibranor (Iqirvo PPAR α/Ύ FDA June 2024) + seladelpar (Livdelzi PPAR Ύ FDA August 2024) + bezafibrate/fenofibrate (off-label)
- PSC male > female (2:1) + strong UC association 75-90% + male UC patients more likely PSC; 5% of UC have PSC
- PSC diagnosis gold standard MRCP: multifocal strictures + dilations = âbeadingâ of bile ducts; pANCA positive 60-80%; no specific autoantibody like PBC
- PSC cholangiocarcinoma risk 10-15% lifetime: difficult to diagnose due to background biliary changes; annual surveillance with MRCP + CA 19-9 (false positive with cholangitis common)
- PSC + IBD CRC surveillance: annual colonoscopy starting at PSC diagnosis (vs 8-10 years for UC alone); higher risk than UC alone
- PSC no effective medical therapy: standard-dose UDCA modest; high-dose UDCA (28-30 mg/kg) is harmful per UDCA-PSC trial; steroids ineffective (unlike AIH overlap); ERCP for dominant strictures
- PSC + hilar cholangiocarcinoma: Mayo protocol = neoadjuvant chemoradiation followed by liver transplant in highly selected centers; outcomes acceptable in early disease