classification, pathogenesis, signs, symptoms, diagnosis with lab findings, scoring system, differential diagnosis and treatment of autoimmune hepatitis

1. PRESENTED BY: DR. RAHUL GUPTA
GUIDE: DR. AMIT SINGH

2.  AIH is a disorder of unknown cause characterized by
unresolving inflammation of the liver.
 It includes:
 Presence of autoimmune antibody
 Evidence of hepatitis(interface being characteristic)
 Elevation of serum globulins

3. Other names
 active chronic hepatitis or chronic active hepatitis
 Chronic aggressive hepatitis
 Lupoid hepatitis
 Plasma cell hepatitis
 Autoimmune chronic active hepatitis

4.  Antibodies are : ANA, ASMA, Anti LKM1
 Atypical pANCA is positive in AIH, PSC, UC
 Anti Neutrophilic Nuclear Antibody (ANNA)
 Other antibodies are:
 Anti SLA
 Anti Actin
 Anti chromatin
 Anti asialoglycoprotein(ASGPR)
 Anti livercytosol Type1
 Presence of these antibodies denote poor prognosis and
relapse after drug withdrawl

5. Classification
1. Type 1
2. Type 2
3. Type 3
Seki T, Kiyosawa K, Inoko H, et al. Association
of autoimmune hepatitis with HLA-Bw54 and
DR4 in Japanese patients. Hepatology. 1990
Dec. 12(6):1300-4.

6. TYPE 1
 Classically in young females
 ANA or Anti Smooth Muscle antibody positive
 Titer usually>1:100
 10% will have an antibody to Soluble Liver
Antigens(SLA)
 Other antibodies: atypical pANCA(90%) Anti
Actin(AAA),Antiasialoglycoprotein,Anti
chromatin,Anti soluble liver antigen.
 Anti Actin antibodies have greater specificity

7. TYPE 1
 Bimodal Age distribution(ages 10-20 and 45-70)
 Female:male 3.6:1
 HLA DR3 or DR4 association
 Associated with extrahepatic manifestations(38%):
 Autoimmune thyroiditis, Graves disease, Chronic UC
 Less coomonly with RA, pericious anemia, systematic
sclerosis, ITP, SLE, coombs positive hemolytic anemia,
leucocytoclastic vasculitis, erythema nodosum
 40% present with acute onset of symptoms similar to
toxic hepatitis or acute viral hepatitis

8. TYPE 2
 Seen in children (2-14yrs)in Meditteranean population
 HLA DR1 or DQB1 association
 Presence of anti liver/kidney microsome
antibodies(anti LKM1)
 Target antigen is cytochromr p4502D6 monooxygenase
 Anti liver cytosol antibody
 Acute or fulminant presentation possible

9. TYPE 3
 antibodies to soluble liver antigen
 lack ANA and anti LKM1 antibodies
 more in women, part of spectrum of type 1 AIH
 elevated gamma globulin: ++
 steroid responsive: ++
 % progression to cirrohis:75

11. PATHOGENESIS
 Pathogenesis is unknown but popular hypothesis
include triggering agent, genetic predisposition and
various determinants of autoantigen display,
immunocyte activation and effector cell expansion
 Triggering agent – drug
infection
toxin

13. Autoimmune hepatitis and chronic
hepatitis C
 8% of white North American adults have Concurrent
infection with HCV
 52% of chronic hepatitis C patients have
autoantibodies
 Interferon therapy can enhance immune
manifestations of AIH and concurrent HCV infection
 Immunosuppressive treatment can increase serum
viral levels in patients with chronic hepatitis C
 Treatment should be appropriate for predominant
disease, based on nature of concurrent immune
disease
Czaja AJ. Autoimmune hepatitis. Sleisenger and Fordtran's
Gastrointestinal and Liver Disease. 6th ed. Philadelphia,

15. CLINICAL PRESENTATION
 similar as chronic hepatitis
 May be confused with acute hepatitis
 Can have acute severe or fulminant presentation,
history of recurrent bouts
 Asymptomatic in 34%-45% cases

16. SYMPTOMS
 Fatigue, Malaise 86%
 Jaundice 77%
 Abdominal Pain 48%
 Pruritis 36%
 Anorexia 30%
 Myalgias 30%
 Diarrhoea 28%
 Fever 18%

17. SIGNS
 Hepatomegaly 78%
 Jaundice 69%
 Splenomegaly 32%
 Concurrent immune disease 38%
 Ascites 20%
 Encephalopathy 14%

18. LAB FINDINGS
 Elevated AST 100%
 Hypergammaglobulinemia 92%
 Increase immunoglobulin G level 91%
 Hyperbilirubinemia 83%
 Alkaline phosphatase >2 times 33%

19.  Immunoserological markers:
 SMA, ANA, anti LKM1-100%
 pANCA -92%(type 1 only)
 Anti asialoglycoprotein 82%
 Anti actin 74%
 Anti chromatin 42%
 Anti liver cytosol 32%(type 2only)
 Anti soluble liver antigen 11-17%

20. DIAGNOSIS

21. Czaja AJ. Diagnosis and management of
autoimmune hepatitis. Clin Liver Dis. 2015 Feb. 19
(1):57-79.
Clinical criteria
Definitive diagnosis
1.Exclude other similar
disease
2.Laboratory findings
3.Histological features
Probable diagnosis
Findings compatible
with AIH but
insufficient for definite
diagnosis

22. Ref: Sleisenger
and fordtrans

25. SCORING SYSTEMS
 Revised original scoring system
 Simplified scoring system

26. Sleiseng
er
fordtran
s page
1146

28. SIMPLIFIED SCORING SYSTEM
 Greater specificity vs original scoring system(90% vs
73%)
 Greater predictability(92% vs 82%)
 Usefel for excluding AIH in patients with other
conditions and concurrent immune features
 Less sensitivity(95% vs 100%)

29. DIFFERENTIAL DIAGNOSIS
 Primary biliary cirrhosis
 Post necrotic cryptogenic cirrhosis
 Primary sclerosing cholangitis
 Acute viral hepatitis

30.  Mild chronic viral hepatitis
 Wilsons disease
 Haemochromatosis
 Alcoholic hepatitis

31. TREATMENT
 Should be based on
 Severity of symptoms
 Degree of elevation in transaminases and IgG
 Histologic findings
 Potential side effects of treatment

32. AASLD RECOMMENDATIONS
 Treat if serum aminotransferases are greater than
10times normal
 Treat if serum aminotransferases are greater than 5
times normal and IgG is elevated to greater than
2times normal, bridging fibrosis or multilobular
necrosis, presence of symptoms
REF:Lichtenstein GR. Use of laboratory testing to guide 6-
mercaptopurine/azathioprine therapy. Gastroenterology. 2004 Nov. 127(5):1558-64

33.  Prednisone
 Azathioprine

34. PREDNISONE
 Glucocorticoid limit T cell activation by inhibiting
cytokine production
 Steroid are lipophilic, diffuse into cell and nucleus
where it inhibits cytokine gene expression and reduce
the activity of nuclear factor ĸB. Type 1 and type 2
cytokine pathway affected and both cellular and
humoral immune response blunted

35. AZATHIOPRINE
6 Thioguanine
6 Mercaptopurine
(Hypoxanthin gaunine Phosphoribosyl
transferase)
Azathioprine
(Non enzymatic)

40. TREATMENT REMISSION
 Disapperance of symptoms
 Normal serum bilirubin and IgG
 Serum aminotransferases normal or less than twice
normal
 Normal hepatic tissue or minimal inflammation and
no interface hepatitis
Strassburg CP, Manns MP. Treatment of
autoimmune hepatitis. Semin Liver Dis. 2009
Aug. 29(3):273-85.

41. TREATMENT REMISSION
Action
 Gradual withdrawl of prednisone
 Discontinuation of azathioprine
 Regular monitoring for relapse
 Histological improvement lacks behind laboratory
resolution by 3 to 8 months, so treatment should be
continued for 3 to 8 months after lab parameters come
normal
Strassburg CP, Manns MP. Treatment of
autoimmune hepatitis. Semin Liver Dis.
2009 Aug. 29(3):273-85.

42. TREATMENT FAILURE
 Worsening clinical laboratory and histologic findings
despite compliance with therapy
 Onset of ascites or encephalopathy
 Increase in aminotransferases or bilirubin by >67%
Action:
 Prednisone 60mg/d or prednisone 30mg/d with
azathioprine 150mg/d * 1 month
 Each schedule induces clinical and biochemical
improvement in 70% but histological improvement
occurs only in 20%

43. TREATMENT FAILURE
 Treatment failure are frequent in patients with
established cirrhosis, HLA – DR 3 or in patients
who present with disease at a younger age and with
a longer duration of symptoms

44. INCOMPLETE RESPONE
 Some or no improvement in clinical , laboratory or
histologic featurse that does not satisfy remission
criteria
 Failure to achieve remission after 3 years
Action:
 Low dose prednisone or azathioprine(2mg/kg daily)
 Indefinite treatment

45. RELAPSE
 An exacerbation after drug withdrawl in patients who enter remission
 Reappearance of histological disease
 AST >3 folds ULN
 Cirrhosis develops commonly
Action:
 Prednisone and azathioprine should be restarted and continued until
clinical and laboratory resolution achieved
 Azathioprine dose increased to 2mg/kg daily and dose of prednisone
decreased
 Azathioprine continued indefinitely
 Alternatively low dose prednisone 10mg/day continued indefinitely
 Liver transplantation

46. LIVER TRANSPLANT: INDICATIONS
 Patients with ascites and hepatic encephalopathy
 Failed glucocorticoid therapy
 HCC
 MELD score>15
 Multilobar necrosis and have atleast one laboratory
parameter which does not normalize within 2weeks of
treatment
 Worsen while on glucocorticoid therapy

48. REFERENCES
 Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirth S. Clinical
features and biochemical data of Caucasian children at diagnosis of
autoimmune hepatitis. J Autoimmun. 2005 Feb. 24(1):79-84.
 Strassburg CP, Manns MP. Treatment of autoimmune hepatitis. Semin Liver
Dis. 2009 Aug. 29(3):273-85.
 Czaja AJ, Carpenter HA, Santrach PJ, et al. Genetic predispositions for the
immunological features of chronic active hepatitis. Hepatology. 1993 Oct.
18(4):816-22.
 Czaja AJ. Diagnosis and management of autoimmune hepatitis. Clin Liver Dis.
2015 Feb. 19 (1):57-79.
 Czaja AJ. Autoimmune hepatitis. Sleisenger and Fordtran's Gastrointestinal and
Liver Disease. 6th ed. Philadelphia, Pa: WB Saunders Company; 1998. 1265-1274.
 Seki T, Kiyosawa K, Inoko H, et al. Association of autoimmune hepatitis with
HLA-Bw54 and DR4 in Japanese patients. Hepatology. 1990 Dec. 12(6):1300-4.
 Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis
Group Report: review of criteria for diagnosis of autoimmune hepatitis. J
Hepatol. 1999 Nov. 31(5):929-38.
 Lichtenstein GR. Use of laboratory testing to guide 6-
mercaptopurine/azathioprine therapy. Gastroenterology. 2004 Nov. 127(5):1558-
64