Autoimmune Hepatitis

Question 1

Define

Answer 1

An inflammatory liver disease of unknown cause characterised by suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens

1. Autoimmune features
2. Hyperglobulinaemia
3. Circulating autoantibodies

Classification based on different autoantibodies
Type 1 (classic) → ANA, ant-smooth muscle antibodies (ASMA), anti-actin antibodies (AAA), antisoluble liver antigen (anti-SLA) Type 2 → antibodies to liver/kidney microsomes (ALKM-1), ALC-1

Question 2

Causes

Answer 2

In a genetically predisposed individual, and environmental agent (e.g. viruses or drugs) may lead to hepatocyte expression of HLA antigens, which then become the focus of a principally T-cell-mediated autoimmune attack

The raised titre of anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver/kidney microsomes (anti-LKM) are NOT thought to directly injure the liver

The chronic inflammatory changes are similar to those seen in chronic viral hepatitis with lymphoid infiltration of the portal tracts and hepatocyte necrosis, leading to fibrosis and, eventually, cirrhosis

TWO major forms of autoimmune hepatitis:

Type 1 (Classic)

• ANA
• ASMA
• Anti-actin antibodies (AAA)
• Anti-soluble liver antigen (anti-SLA)

Type 2

• Antibodies to liver/kidney microsomes (ALKM-1)
• Antibodies to liver cytosol antigen (ALC-1)

Question 3

Risk factors

Answer 3

Personal or FHx of autoimmune disease (e.g. T1 diabetes or vitiligo)

Question 4

Epidemiology

Answer 4

• Type 1: occurs in ALL age groups (but mainly young women)
• Type 2: generally occurs in girls and young women

Question 5

Symptoms

Answer 5

May be asymptomatic and discovered incidentally through abnormal LFT

Insidiously present with:

• Malaise
• Fatigue
• Anorexia
• Weight loss
• Nausea
• Jaundice
• Amenorrhoea
• Epistaxis

Acute hepatitis (25%) presents with:

• Fever
• Anorexia
• Jaundice
• Nausea/Vomiting/Diarrhoea
• RUQ pain
• Some may present with serum sickness (e.g. arthralgia, polyarthritis, maculopapular rash)

NOTE: check for personal or family history of other autoimmune diseases

A full history is important to rule out other causes of hepatitis (e.g. viral, alcoholic)

Question 6

Signs

Answer 6

Stigmata of chronic liver disease (e.g. spider naevi)

Ascites, oedema and hepatic encephalopathy are late features

Cushingoid features may be present even before the administration of steroids

Question 7

Investigations

Answer 7

Bloods:

LFTs:

• High: AST, ALT, GGT, ALP and Bilirubin
• Low: albumin (in severe disease)

Clotting:

• High PT (in severe disease)

FBC:

• Low Hb, platelets and WCC (if hypersplenism from portal hypertension)

Hypergammaglobulinaemia

• Presence of ANA, ASMA and Anti-LKM antibodies

Liver Biopsy:

• Needed to establish diagnosis and check whether hepatitis or cirrhosis

To rule out other causes of liver disease:

• Viral serology
• Urinary copper/caeruloplasmin
• Ferritin and transferrin saturation
• a1 antitrypsin
• Anti-mitochondrial antibodies (PBC)

US, CT or MRI of liver and abdomen

• Visualise structural lesions

ERCP

• To rule out PSC