Autoimmune Hepatitis Flashcards
Define autoimmune hepatitis.
Chronic hepatitis of unknown aetiology, characterised by autoimmune features, hyperglobulinaemia + autoantibodies.
What are the types of autoimmune hepatitis?
Type I (classic)
- ANA
- anti-smooth muscle antibodies - anti-SMA
- perinuclear anti-neutrophil cytoplasmic auto-antibody
- anti-soluble liver antigen/liver-pancreas positive
Type II
- anti- liver/kidney microsomes- ALKM-1
- +/- anti-liver cytosol specific -positive
How common is AI hepatitis?
- 4:1 females
- Most common in Northern European
- AIH type 1 most common
- Bimodal at 10-30yrs and 40-60yr
- Type 2 mostly affects children
What is the pathophysiology of autoimmune hepatitis?
In a genetically pre-disposed person, an environmental agent can trigger a pathogenic process leading to liver necrosis and fibrosis.
Type I associated with HLA-DR3 and HLA-DR4
Environmental triggers include viruses (e.g.measles, CMV, HAV, HCV), drugs (e.g. methyldopa, diclofenac, statin) and herbal agents (e.g. black cohosh and dai-saiko-to)
How common is autoimmune hepatitis?
Type I occurs in all age groups (although mainly in young women)
Type 2 is generally a disease of girls and young women
What are the risk factors for autoimmune hepatitis?
- Female
- Genetic predisposition - type 1 AIH: HLA-DR3 and HLA-DR4; type 2 AIH:HLA-DQB1 and HLA-DRB1.
- Immune dysregulation - e.g. thyroiditis, type 1 diabetes, ulcerative colitis, coeliac disease, and rheumatoid arthritis.
Other: measles virus, cytomegalovirus, EBV, hepatitis A, C,D and certain drugs.
What is the typical presentation of autoimmune hepatitis?
- Asymptomatic
- Insidious onset -of:
- malaise fatigue, anorexia and weight loss, nausea, jaundice, amenorrhoea, epistaxis
1. Acute hepatitis (25%) - fever, anorexia, jaundice, nausea, vomiting, diarrhoea, RUQ pain. Some may present with serum sickness (e.g arthralgia, polyarthritis, maculopapular rash) - Keratoconjunctivitis sicca - may be associated
- Personal/FH of AI disease - type 1 diabetes, vitiligo.
- Must take a full history to rule out other causes of hepatitis e.g. alcohol, drugs.
How do you diagnose AIH?
Diagnosis by:
- Other AI diseases present
- LFTs - ALT and AST most raised, but others also abnormal
- Auto-antibodies and hypergammaglobulinaemia - raised IgG , ANA, SMAs/anti-actin Abs. Anti-LKM-1 characteristic of type 2 AIH.
- Liver biopsy - showing periportal lesions or interface hepatitis. Many plasma cells. Causes fibrosis and bile duct changes (25%).
Rule out other causes…
- Viral serology - hep B and C
- Caeruloplasmin
- Urinary copper (for Wilson’s)
- Iron studies - ferritin and transferrin saturation (haemochromatosis)
- Alpha-1 antitrypsin - for deficiency
- Antimitochondrial antibodies - in PBC
What is the management of autoimmune hepatitis?
Treatment given when there is active disease when symptoms or disease activity are severe e.g. very high ALT/AST, necrosis on histology. Don’t need to treat those with cirrhosis with inactive disease.
Active severe disease…
- High dose corticosteroids - monotherapy for 7-14days.
- OR Immunosuppressant - azathioprine for >6months (check TPMT)
If no change and very severe…
- Emergency liver transplant
Minimally active disease…
- Observation and monitoring every 3-6 months
What are the indications for treating autoimmune hepatitis?
- Aminotransferases >10x upper limit of normal
- Symptomatic
- Histology - significant interface hepatitis, bridging necrosis or multiacinar necrosis
What are the complications of AI hepatitis?
- HCC - but rare without HBV/HCV; screen every 6 months
- ESLD
Corticosteroid related:
- Osteoporosis
- DM
- Hypertension
- Truncal obesity
- Acne, facial rounding, dorsal hump formation
- Growth impairment (children)
- Cataracts
- Depression/psychosis
Azathioprine related:
- Malignancy
- Infection
- BM suppression
- Cholestasis
- Pancreatitis
- Veno-occlusive disease
- Skin rash
What is the prognosis with AIH?
Poor prognosis with 5yr survival 50% without treatment
Most respond to treatment within 2 weeks
