Autoimmune Hepatitis

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Autoimmune Hepatitis
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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

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Laboratory Data
AST 214
ALT 272
Alk Phos 74
Total Bili 0.6
Total Protein 8.0
Alb 3.0
ANA 11280
ASMA 180
AMA -
Viral Serologies -
Ferritin 75
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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

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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

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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 Gastro3399-103
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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

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Clinical Manifestations

• Symptoms
• Fatigue 85
• Jaundice 77
• Abdominal pain 48
• Pruritus 36
• Anorexia 30
• Polymyalgias 30
• Diarrhea 28
• Fevers 18

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Clinical Manifestations

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

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Clinical Manifestations

• Laboratory features
• Elevated AST 100
• Hypergammaglobulinemia 92
• Inc immunoglobulin G level 91
• Hyperbilirubinemia 83
• Alk Phos gt2x 33

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Differential Diagnosis

• Wilsons disease
• A1AT deficiency
• Hemochromatosis
• Viral hepatitis
• Drug induced hepatitis

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Liver Histology
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Autoimmune Histology
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Diagnosis
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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

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Diagnostic Scoring System for Atypical Autoimmune
Hepatitis
Category Factor Score Category Factor Score
Gender female 2 Other immune Non-hepatic of immune nature 2
APAST gt3 lt1.5 -2 2 autoabs Anti-SLA/LP,actin,LC1 2
glob gt2.0 1.5-2.0 1.0-1.5 lt1.0 3 2 1 0 histology Interface hepatitis Plasma cells Rosettes None of above 3 1 1 -5
ANA,SMA, LKM1 gt180 180 140 lt140 3 2 1 0 HLA DR3 or DR4 1
AMA positive -4 Rx response Remission alone Remission w/relapse 2 3
Viral markers Positive negative -3 3 Pretreatment definite dx probable dx gt15 10-15
drugs Yes no -4 1 Post-treatment definite dx probable dx gt17 12-17
alcohol lt25 gm/d gt60 gm/s 2 -2
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Subclassification of AIH

• Type I
• Type II
• Type III

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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

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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

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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

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Prognostic Indices

• Laboratory findings at presentation
• ASTgt10x nl 50, 3-year mortality
• ASTgt5x nl GGTgt2x 90, 10-yr mortality
• ASTlt10x nl GGTlt2x 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

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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

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Treatment
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Indications for Treatment
Absolute Relative
Serum ASTgt10x uln Symptoms (fatigue, arthralgia, jaundice)
Serum ASTgt5x uln and globulin gt2x nl Serum AST and globulin less than absolute criteria
Bridging necrosis or multiacinar necrosis Interface hepatitis
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Treatment Regimens
Prednisone only Combination (Pred AZA)
Week 1 60 mg 30 mg50 mg
Week 2 40 mg 20 mg50 mg
Week 3 30 mg 15 mg50 mg
Week 4 30 mg 15 mg50 mg
Maintenance until endpoint 20 mg 10mg50 mg

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Reasons for Preference

• Prednisone
• Cytopenia
• TPMT deficiency
• Pregnancy
• Malignancy
• Short course lt6 mos

• Combination
• Postmenopausal state
• Osteoporosis
• Brittle diabetes
• Obesity
• Acne
• Emotional Lability
• Hypertension

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Treatment Endpoints

• Remission
• 10-40 of patients
• Treatment Failure
• Incomplete Response
• Drug Toxicity

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Remission

• 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

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Treatment Failure

• 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

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Incomplete Response

• 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

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Management of Relapse after Drug Withdrawal

• Relapse at least twice
• Indefinite low dose prednisone
• Indefinite low dose azathioprine

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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

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Hepatocellular Carcinoma

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

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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

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Case Presentation
AST 19
ALT 12
AP 54
Total protein/albumin 7.3/4.6
Total bilirubin 0.6
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