Download Autoimmune Hepatitis

Autoimmune Hepatitis
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
Laboratory Data
AST
214
ALT
Alk Phos
Total Bili
Total Protein
272
74
0.6
8.0
Alb
ANA
ASMA
3.0
1:1280
1:80
AMA
Viral Serologies
Ferritin
75
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
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
Epidemiology
► 1.9
cases per 100,000 incidence of
Autoimmune Hepatitis in western Europe
Boberg K. 1998: Scad J Gastro;33:99-103
► Frequency
of AIH among patients with
chronic liver disease is 11%
► Accounts
US
for 5.9% of transplantations in the
Background
► 40%
of patients with untreated severe
disease die within 6 mos of dx
► 40% develop cirrhosis
 54% develop esophageal varices
►20%
► An
die of hemorrhage
acute onset of illness is seen in 40%
patients
► Prednisone and azathioprine are mainstay of
treatment
Clinical Manifestations
► Symptoms








Fatigue 85%
Jaundice 77%
Abdominal pain 48%
Pruritus 36%
Anorexia 30%
Polymyalgias 30%
Diarrhea 28%
Fevers 18%
Clinical Manifestations
► Physical







Findings
Hepatomegaly 78%
Jaundice 69%
Splenomegaly 32%
Spider nevi 58%
Ascites 20%
Encephalopathy 14%
Concurrent immune disease 48%
Clinical Manifestations
► Laboratory





features
Elevated AST 100%
Hypergammaglobulinemia 92%
Inc immunoglobulin G level 91%
Hyperbilirubinemia 83%
Alk Phos >2x 33%
Differential Diagnosis
► Wilson’s
disease
► A1AT deficiency
► Hemochromatosis
► Viral hepatitis
► Drug induced hepatitis
Liver Histology
Autoimmune Histology
Diagnosis
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
Diagnostic Scoring System for
Atypical Autoimmune Hepatitis
Category
Factor
Score
Category
Factor
Score
Gender
female
+2
Other immune
Non-hepatic of
immune nature
+2
AP:AST
>3
<1.5
-2
+2
autoabs
AntiSLA/LP,actin,LC1
+2
glob
>2.0
1.5-2.0
1.0-1.5
<1.0
+3
+2
+1
0
histology
Interface hepatitis
Plasma cells
Rosettes
None of above
+3
+1
+1
-5
ANA,SMA, LKM1
>1:80
1:80
1:40
<1:40
+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
>15
10-15
Yes
no
-4
+1
Post-treatment
definite dx
probable dx
>17
12-17
<25 gm/d
>60 gm/s
+2
-2
drugs
alcohol
Subclassification of AIH
► Type
I
► Type
II
► Type
III
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
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
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
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
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
Treatment
Indications for Treatment
Absolute
Relative
Serum AST>10x uln
Symptoms (fatigue,
arthralgia, jaundice)
Serum AST>5x uln and
globulin >2x nl
Serum AST and globulin
less than absolute
criteria
Interface hepatitis
Bridging necrosis or
multiacinar necrosis
Treatment Regimens
Week 1
Prednisone only Combination
(Pred + AZA)
60 mg
30 mg+50 mg
Week 2
40 mg
20 mg+50 mg
Week 3
30 mg
15 mg+50 mg
Week 4
30 mg
15 mg+50 mg
Maintenance
until endpoint
20 mg
10mg+50 mg
Reasons for Preference
► Prednisone





Cytopenia
TPMT deficiency
Pregnancy
Malignancy
Short course <6 mos
► Combination







Postmenopausal state
Osteoporosis
Brittle diabetes
Obesity
Acne
Emotional Lability
Hypertension
Treatment Endpoints
► Remission
 10-40% of patients
► Treatment
Failure
► Incomplete Response
► Drug Toxicity
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
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
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
Management of Relapse after Drug
Withdrawal
► Relapse
at least twice
 Indefinite low dose prednisone
 Indefinite low dose azathioprine
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
Hepatocellular Carcinoma
► Uncommon
in the absence of cirrhosis or
coexisting hepatitis B or C
► If cirrhosis
 RUQ ultrasound
 Alfa fetoprotein every 6-12 months
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
Case Presentation
AST
19
ALT
12
AP
54
Total protein/albumin
7.3/4.6
Total bilirubin
0.6
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