Key Facts

Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease that, if untreated, leads to cirrhosis and liver failure. It responds well to immunosuppressive therapy in most cases.

Epidemiology

Incidence ~1-2 per 100,000 per year. Prevalence ~10-17 per 100,000. Female predominance (4:1). Bimodal onset: adolescence/young adulthood and middle age (40-60 years). Can present at any age including elderly. All ethnic groups affected.

Aetiology

Autoimmune — likely a combination of genetic predisposition (HLA-DR3 and HLA-DR4) and environmental triggers (viral infections, drugs — minocycline, nitrofurantoin, statins). Associated autoimmune conditions: autoimmune thyroid disease, coeliac disease, T1DM, RA, Sjögren syndrome, vitiligo.

Pathophysiology

Loss of immune tolerance to hepatocyte antigens. Molecular mimicry between viral/drug antigens and hepatocyte surface proteins may trigger the response. CD4+ T helper cells recognise hepatocyte autoantigens presented by HLA class II → cytokine release → CD8+ cytotoxic T cell-mediated hepatocyte destruction. Plasma cell infiltration is prominent. Interface hepatitis (destruction of hepatocytes at the portal-parenchymal boundary) is the histological hallmark. Untreated, progressive fibrosis leads to cirrhosis.

Typical Presentation

• Insidious onset: fatigue, malaise, anorexia
• Jaundice (may be fluctuating)
• RUQ discomfort, hepatomegaly
• Amenorrhoea (in premenopausal women)
• Arthralgia (common)

Acute Presentation (~25%)

• Acute hepatitis mimicking viral hepatitis
• Marked jaundice, very high ALT (>1000)
• Rarely fulminant hepatic failure

Cirrhotic Presentation (~25%)

• Presents with established cirrhosis and complications
• May be incidental finding

Associated Conditions

• Autoimmune thyroiditis
• Coeliac disease
• Type 1 diabetes
• Ulcerative colitis (overlap with PSC)

Red Flags

• Acute liver failure (encephalopathy, coagulopathy)
• Rapidly deteriorating liver function
• Features of decompensated cirrhosis at presentation

Bloods

• LFTs: raised ALT/AST (often markedly); ALP may be mildly raised
• Immunoglobulins: raised IgG (polyclonal) — characteristic
• Autoantibodies: ANA, SMA (anti-smooth muscle — anti-actin), anti-LKM1 (liver-kidney microsomal type 1), anti-LC1 (liver cytosol type 1), anti-SLA (soluble liver antigen — most specific)
• FBC: may show cytopaenias (hypersplenism if cirrhotic)
• INR: synthetic function
• Exclude viral hepatitis: HBsAg, anti-HCV, anti-HAV IgM, anti-HEV IgM
• Caeruloplasmin: exclude Wilson disease (especially if young)
• TPMT/NUDT15: before starting azathioprine

Imaging

• USS abdomen: liver assessment, cirrhosis features
• FibroScan: fibrosis staging

Special Tests

• Liver biopsy: essential for diagnosis — shows:
  • Interface hepatitis (piecemeal necrosis)
  • Plasma cell-rich infiltrate in portal and periportal areas
  • Hepatocyte rosetting
  • Emperipolesis (lymphocyte penetration into hepatocytes)
  • Fibrosis staging (Ishak/METAVIR)
• Simplified AIH diagnostic score (IAIHG): autoantibodies + IgG level + histology + absence of viral hepatitis; ≥7 = definite, ≥6 = probable

Non-pharmacological

• Avoid hepatotoxic drugs and excessive alcohol
• Bone protection: calcium/vitamin D with long-term steroids; DEXA scan
• Vaccination: influenza, pneumococcal, COVID-19 (before immunosuppression if possible)

Pharmacological

• Induction: prednisolone 30-40 mg/day (or budesonide 9 mg/day if non-cirrhotic — less systemic side effects) for 2-4 weeks, then taper by 5 mg/week
• Maintenance: azathioprine 1-2 mg/kg/day (check TPMT/NUDT15 first) as steroid-sparing agent; introduced once ALT improving (usually week 2-4)
  • Target: complete biochemical remission (normal ALT, IgG)
  • Most require azathioprine for ≥2 years; many indefinitely
• Steroid taper: aim to maintain on azathioprine monotherapy at lowest effective dose
• Second-line (azathioprine intolerance/failure): mycophenolate mofetil 1-1.5 g BD; tacrolimus; ciclosporin
• Acute severe/fulminant AIH: high-dose methylprednisolone 1 g IV for 3 days; early transplant assessment if not responding
• Relapse: common on steroid withdrawal (~50-80%); re-induce with steroids + optimise azathioprine

Surgical/Interventional

• Liver transplantation: for decompensated cirrhosis, acute liver failure not responding to immunosuppression; 5-year post-transplant survival >80%; AIH recurrence in graft ~20-40%

Referral Criteria

• All suspected AIH to hepatology for biopsy and specialist management
• Transplant assessment if acute liver failure or decompensated cirrhosis
• Annual monitoring: LFTs, IgG, FBC (azathioprine toxicity), bone density

With treatment, 80% achieve biochemical remission. 10-year survival with treatment is >90% (comparable to age-matched general population). Without treatment, ~40% with severe disease die within 6 months. Relapse on steroid withdrawal occurs in 50-80%. Cirrhosis develops in ~30% despite treatment (often those presenting late). Post-transplant 5-year survival >80%, but AIH recurrence in ~20-40% of grafts. HCC risk is lower than in viral/alcoholic cirrhosis but surveillance is still recommended.

AIH Classification

Simplified AIH Diagnostic Score (IAIHG)