Autoimmune Hepatitis

1. Autoimmune Hepatitis

2. Case Presentation • 54 yo woman with abnormal liver function test • 9 years ago patient with ele lfts • No complaints • PMH: migraine headaches, arthritis, bilateral tubal ligation, repair of ganglion cyst • Meds: Prempro, Imitrex • SH: rare alcohol, no tobacco • FH: no history of liver disease • PE: weight 104 lbs, no stigmata of Chronic liver disease

3. Laboratory Data

4. Other Data • Sono: 3 mm CBD, normal gallbladder, increase echogeneity c/w fatty liver • Liver Biopsy: moderate piecemeal necrosis with early fibrosis, expanded portal tracts with plasma cells • DX: Autoimmune Hepatitis • RX: Steroids and Imuran

5. Definition • Self perpetuating hepatocellular inflammation of unknown cause • Characterized by the presence of: • periportal hepatitis • Hypergammaglobulinemia • Serum liver-associated autoantibodies • Exclusion of other chronic liver diseases

6. Epidemiology • 1.9 cases per 100,000 incidence of Autoimmune Hepatitis in western Europe • Frequency of AIH among patients with chronic liver disease is 11% • Accounts for 5.9% of transplantations in the US Boberg K. 1998: Scad J Gastro;33:99-103

7. Background • 40% of patients with untreated severe disease die within 6 mos of dx • 40% develop cirrhosis • 54% develop esophageal varices • 20% die of hemorrhage • An acute onset of illness is seen in 40% patients • Prednisone and azathioprine are mainstay of treatment

8. Clinical Manifestations • Symptoms • Fatigue 85% • Jaundice 77% • Abdominal pain 48% • Pruritus 36% • Anorexia 30% • Polymyalgias 30% • Diarrhea 28% • Fevers 18%

9. Clinical Manifestations • Physical Findings • Hepatomegaly 78% • Jaundice 69% • Splenomegaly 32% • Spider nevi 58% • Ascites 20% • Encephalopathy 14% • Concurrent immune disease 48%

10. Clinical Manifestations • Laboratory features • Elevated AST 100% • Hypergammaglobulinemia 92% • Inc immunoglobulin G level 91% • Hyperbilirubinemia 83% • Alk Phos >2x 33%

11. Differential Diagnosis • Wilson’s disease • A1AT deficiency • Hemochromatosis • Viral hepatitis • Drug induced hepatitis

12. Liver Histology

13. Autoimmune Histology

14. Diagnosis

15. Diagnostic Criteria • Clinical criteria • Presence of characteristic clinical features • Liver histology • Exclusion of other diseases • Scoring criteria • Assess the strength of the diagnosis • Pretreatment and post-treatment • Helpful with variant or atypical forms of AIH

16. Diagnostic Scoring System for Atypical Autoimmune Hepatitis

17. Subclassification of AIH • Type I • Type II • Type III

18. Type 1 AIH • Diagnostic autoantibodies: ANA, ASMA • Age: Bidmodal (10-20 and 45-70) • % Women: 78 • % Concurrent immune diseases: 41 • Elevated gamma globulin: +++ • Steroid responsiveness: +++ • Progression to cirrhosis (%): 45

19. Type II AIH • Diagnostic autoantibodies: LKM1 • Age: Pediatric (2-14), rare adults (4%) • % Women: 89 • % Concurrent autoimmune disease: 34 • Elevated gamma-globulins: + • Steroids responsive: ++ • % progression to cirrhosis: 82

20. Type III AIH • Diagnostic autoantibodies: SLA and LP • Age: adults (30-50) • % Women: 90 • % Concurrent autoimmune disease: 58 • Elevated gamma-globulin: ++ • Steroid responsive: +++ • % progression to cirrhosis: 75

21. Prognostic Indices • Laboratory findings at presentation • AST>10x nl: 50%, 3-year mortality • AST>5x nl + GGT>2x; 90%, 10-yr mortality • AST<10x nl + GGT<2x; 49%, cirrhosis at 15 yr; 10% 10-yr mortality • Histologic findings at presentation • Periportal hepatitis: 17%,cirrhosis at 5 yr; Nl 5 yr survival • Bridging necrosis: 82%, cirrhosis of 5 yr; 45%, 5-yr mortality • Cirrhosis: 58%, 5 yr-mortality

22. Recommendations • Diagnosis of AIH requires aminotransferase and globulin levels; detection of ANA +/or SMA, anti-LKM1; and histology • Diagnostic criteria for AIH should be applied to all patients • If the diagnosis is not clear, a scoring method should be used

23. Treatment

24. Indications for Treatment

25. Treatment Regimens

26. Prednisone Cytopenia TPMT deficiency Pregnancy Malignancy Short course <6 mos Combination Postmenopausal state Osteoporosis Brittle diabetes Obesity Acne Emotional Lability Hypertension Reasons for Preference

27. Treatment Endpoints • Remission • 10-40% of patients • Treatment Failure • Incomplete Response • Drug Toxicity

28. Criteria Disappearance of symptoms Normal bilirubin + globulin levels Transaminases normal or less than 2x Normal histology or minimal inflammation Action Gradual withdrawal of prednisone Discontinuation of azathioprine Regular monitoring for relapse Remission

29. Criteria Worsening clinical, labs and histology despite compliance Inc transaminasis by 67% Development of jaundice, ascites or hepatic encephalopathy Action Pred 60 mg/d or pred 30 mg/d with aza 150 mg/d x 1 mo Reduction of the dose each month of improvement until maintenance levels Treatment Failure

30. Criteria Some or no improvement in clinical,labs and histology during therapy Failure to achieve remission after 3 years No worsening of condition Action Reduction of dose to lowest levels possible to prevent worsening Indefinite treatment Incomplete Response

31. Management of Relapse after Drug Withdrawal • Relapse at least twice • Indefinite low dose prednisone • Indefinite low dose azathioprine

32. Management of Suboptimal Response to Initial Therapy • Alternative medications • Cyclosporine, 6MP, ursodeoxycholic acid, budesonide, methotrexate, cyclophosphamide and mycophenolate mofetil • Liver Transplantation • 5 year graft survival 83-92% • Disease recurrence is mild and easily managed

33. Hepatocellular Carcinoma • Uncommon in the absence of cirrhosis or coexisting hepatitis B or C • If cirrhosis • RUQ ultrasound • Alfa fetoprotein every 6-12 months

34. Recommendations • High dose prednisone alone or prednisone and aza should be used in treatment failures • Corticosteroid therapy should be considered in the decompensated patient • Liver transplantation should be considered in the decompensated patient unable to undergo salvage therapy

35. Case Presentation What would do next?