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Autoimmune Hepatitis

BSG guidelines for diagnosis and management of autoimmune hepatitis. Published: Apr 2025.

Background Information

Risk Factors

More common in females (3:1)

 

Patients may have associated autoimmune diseases:

  • Autoimmune thyroid disease
  • T1DM
  • Coeliac disease
  • Vitiligo
  • Rheumatoid arthritis

Clinical Features

Up to 40% patients are asymptomatic, often detected via incidental abnormal LFTs.

 

There are 2 main clinical patterns:

Non-specific presentation
  • Amenorrhoea
  • Arthralgia
  • Fatigue, malaise
  • Nausea, vomiting, anorexia
  • Weight loss
Acute hepatitis-like presentation
  • Jaundice
  • Flu-like symptoms
  • RUQ pain

Complications

Key complications:

  • Decompensated liver disease
  • Cirrhosis and hepatocellular carcinoma

Diagnosis

Diagnostic approach (all 3 steps are necessary for diagnosis):

  • Step 1: exclude alternative causes of liver diseases
  • Step 2: LFTs and serology (blood tests)
  • Step 3: liver biopsy

Excluding Alternative Causes of Liver Diseases

Exclude biliary obstruction
  • Liver ultrasound – all patients
  • MRCP – if there is jaundice / ↑ ALP
Viral hepatitis and infection screen All patients:

  • Hep B (HBsAg)
  • Hep C (Anti-HCV)
  • HIV

In acute / icteric presentations, also:

  • Hep A and E
  • CMV
  • EBV

Also consider HSV and varicella zoster in immunocompromised patients

Exclude metabolic / genetic liver disease
  • Ferritin + transferrin saturation (for haemochromatosis)
  • Ceruloplasmin (for Wilson’s disease)
  • A1AT level (for alpha-1 antitrypsin deficiency)
  • Check for drug-induced liver injury, ischaemic liver injury and congestive hepatopathy

Blood Tests

LFTs

Autoimmune hepatitis typically gives a hepatocellular LFT pattern

  • ↑↑ AST and ALT (often <1,000 IU/L)
  • Normal ALP and GGT

 

In acute disease:

  • ↑ Bilirubin (but ALP is still normal / mildly elevated)
  • ↑ INR

Serology

1st line antibodies
  • Anti-SMA (anti-smooth muscle antibodies)
  • ANA (antinuclear antibodies)
  • Anti-LKM-1 (anti-liver-kidney microsomal antibody type 1)
  • ↑ IgG
Additional antibody tests
  • Anti-SLA/LP (anti-soluble liver antigen / liver pancreas antibody) – highly specific
  • Anti-LC1 (anti-liver cytosol antibody type 1)
  • ↑ pANCA (non-specific)

There are 2 main types of serology patterns in autoimmune hepatitis (but it is of limited clinical significance):

  • Type 1 (most common): +ve anti-SMA and ANA
  • Type 2: +ve anti-LKM-1 and anti-LC1
  • Anti-SLA/LP can be present in either type and is highly specific

Liver Biopsy

If autoimmune hepatitis is likely (i.e. other causes of liver disease excluded, and serology is suggestive), liver biopsy should be performed routinely (unless the risks of biopsy clearly outweigh the benefits)

 

Typical histological findings:

  • Interface hepatitis
  • Portal lymphoplasmacytic infiltrate
  • Lobular hepatitis

Liver biopsy is crucial in autoimmune hepatitis to confirm the diagnosis, exclude disease mimics, detect overlap syndromes (e.g. with PBC and PSC), and assess the degree of fibrosis.

Unlike many other autoimmune or metabolic liver diseases (PSC, PBC, haemochromatosis and Wilson’s disease), which do NOT routinely require liver biopsy to confirm diagnosis, autoimmune hepatitis is an exception that typically requires a routine liver biopsy for diagnostic confirmation.

Management

Definitive Management

Most patients would need immunosuppressive treatment (regardless of symptoms) with an induction-maintenance strategy.

1st line
  • Prednisolone for induction, and
  • Azathioprine for maintenance
2nd line
  • Mycophenolate mofetil (for azathioprine intolerance / contraindicated), or
  • Tacrolimus (for inadequate response)

The treatment goal is to normalise AST, ALT and IgG. Once biochemical remission is achieved, prednisolone can be gradually tapered and stopped, while azathioprine is continued as maintenance therapy.

Ensure to check TPMT activity before starting azathioprine. Patients with absent or very low TPMT activity should NOT receive azathioprine, as they are at risk of severe myelosuppression.

TPMT is responsible for metabolising azathioprine metabolites. Therefore, absent or markedly reduced TPMT activity leads to accumulation of active azathioprine metabolites, resulting in bone marrow toxicity and myelosuppression.

References

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