Autoimmune Hepatitis

Question 1

Autoimmune hepatitis is a chronic inflammatory disease of unknown etiology, characterised by T-cell mediated attack against hepatocytes leading to progressive liver damage, cirrhosis and failure.

Occurs more in females (4:1)
Bimodal age distribution - childhood/adolescent and 40-60 years

Question 2

Pathogenesis of AIH

Answer 2

1. Genetic predisposition: HLA-DRB1
2. T-cell immune mediated hepatocyte injury
   - CD4+ T helper cells (Th1 and Th7) -> CD8+ T cytotoxic cells attack hepatocytes
3. Autoantibodies contribute to antigen presentation and T-cell activation (hypergammaglobulinaemia IgG)
4. Pro-inflammatory cytokines (TNF-a, INF-y, IL-17) contribute to liver damage

Question 3

Clinical presentation of patients with AIH

Answer 3

1. Middle age women, premenopause
   (females > males 3:1)
2. Incidental findings of chronic liver disease through LFT or associated autoimmune disease
3. Insidious, non-specific chronic hepatitis
   - fatigue, malaise, lethargy, anorexia, abdominal discomfort, arthralgia
   - Jaundice and pruritus
4. Acute hepatitis with autoimmune symptoms
   - Marked jaundice, high transaminase
   - Coagulopathy
   - Encephalopathy

Question 4

What are the autoimmune conditions associated with autoimmune hepatitis?

Answer 4

1. RA
2. Thyroiditis - Hashimoto, Graves
3. Sjogren syndrome
4. SLE
5. IBD (UC > CD)
6. Pernicious anaemia
7. Coeliac disease
8. IDDM (type 1 DM)
9. Vitiligo
10. AIHA and ITP
11. Concurrent PSC > PBC

Question 5

What are the investigations for autoimmune hepatitis?

Answer 5

Diagnostic tests
1. Autoantibodies
- Type 1: ANA, anti-SMA, HLA B8, HLA DRw3
- Type 2: anti-LKM1
2. LFT - raised ALT > AST (> 5x ULN)
(normal to mild ALP and GGT, if significantly elevated - overlapping PBC/PSC)
3. IgG raised (in PBC IgM is raised)
4. Liver biopsy
- Mononuclear infiltrates of portal and periportal areas, piecemeal necrosis -> fibrosis -> cirrhosis

Other important tests
1. FBC - mono to pancytopenia
2. Coagulation panel
3. Exclude viral hepatitis (Hep A, Hep B, Hep C)
4. Exclude Wilsons - caeruloplasmin
5. Exclude haemochromatosis - iron panel
6. Exclude PBC and PSC

Question 6

Diagnostic Criteria for AIH

Answer 6

1. Autoantibodies titre
   - ≥1:40 or ≥1:80
2. IgG levels
   - > ULN or > 1.1x ULN
3. Liver histology
   - Compatible or typical for AIH
4. Absent of viral hepatitis

Interpretation:
Probable AIH: 6 points
Definite AIH: ≥7 points

Question 7

Classification of AIH

Answer 7

Type 1 AIH: ANA and/or ASMA
Type 2 AIH: anti-LKM1 or LC-1
AIH-PHC overlap: with AMA positive or histological evidence
AIH-PSC overlap: with cholangiographic evidence

Question 8

Complications of AIH

Answer 8

1. Liver cirrhosis
2. HCC transformation

Question 9

What are the treatment for AIH?

Answer 9

1. Induction of remission
   - High dose prednisolone, or
   - Lower dose prednisolone + azathioprine
   - Possible budesonide
2. Maintenance of remission
   - Low dose prednisolone (5-10mg), or
   - Azathioprine monotherapy (1-2mg/kg/day)
3. Refractory cases
   - MMF, calcineurin inhibitors
4. Liver transplant

Question 10

What is the prognosis of untreated severe AIH?

Answer 10

40% survivors develop cirrhosis
40% mortality in 6 months

Relapse rates after treatment withdrawal very high
(50-90% within 1-3 years).

Question 11

Comparison between PBC, PSC and AIH

Answer 11