Autoimmune Hepatitis
Summary
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterised by interface hepatitis, hypergammaglobulinaemia (particularly IgG), and circulating autoantibodies. It predominantly affects females and can present at any age. AIH is classified into two main types based on autoantibody profile: Type 1 (ANA/SMA positive) and Type 2 (LKM-1/LC-1 positive). Untreated AIH leads to progressive fibrosis and cirrhosis. However, the condition is highly responsive to immunosuppressive therapy, with corticosteroids and azathioprine achieving remission in 80-90% of patients. Early diagnosis and treatment are essential to prevent progression to cirrhosis and liver failure.
Key Facts
- Prevalence: 10-17 per 100,000 in Europe
- Sex ratio: Female:Male = 4:1
- Age of onset: Bimodal (10-30 years; 40-60 years)
- Types: Type 1 (ANA, SMA) — most common; Type 2 (LKM-1) — younger, more severe
- Key finding: Elevated IgG, positive autoantibodies, interface hepatitis
- Treatment: Prednisolone + Azathioprine → Azathioprine maintenance
Clinical Pearls
Think AIH in Any Unexplained Hepatitis: AIH can mimic viral hepatitis, drug-induced liver injury, and other liver diseases. Check autoantibodies and IgG in any patient with raised transaminases.
The 80-90% Response Rule: AIH responds well to immunosuppression. Failure to respond should prompt review of diagnosis, adherence, or consideration of overlap syndrome.
Type 2 AIH in Children: Type 2 AIH is more common in children, more severe, and more likely to relapse. These patients often need lifelong treatment.
Why This Matters Clinically
AIH is one of the few liver diseases that responds dramatically to treatment. Early recognition prevents cirrhosis and liver transplant. Untreated, it has a 5-year mortality of 50% in severe cases. With treatment, 10-year survival exceeds 90%.
Incidence & Prevalence
- Incidence: 0.9-2.0 per 100,000 per year
- Prevalence: 10-17 per 100,000 (Europe)
- Geographic variation: More common in Northern Europe, Scandinavia
Demographics
| Factor | Details |
|---|---|
| Sex | Female predominance (70-80%) |
| Age | Bimodal: peak at 10-30 and 40-60 years |
| Ethnicity | All ethnic groups; may be more severe in Black patients |
Risk Factors
| Factor | Details |
|---|---|
| Genetic | HLA-DR3, HLA-DR4 |
| Autoimmune diseases | Associated with thyroid disease, RA, T1DM, UC, coeliac |
| Medications | Minocycline, nitrofurantoin can trigger AIH-like syndrome |
Mechanism
Step 1: Immune Dysregulation
- Loss of tolerance to hepatocyte antigens
- Genetic susceptibility (HLA associations)
- Environmental triggers (viruses, drugs, toxins)
Step 2: Autoantibody Production
- ANA, SMA (Type 1)
- LKM-1, LC-1 (Type 2)
- Autoantibodies are markers, not directly pathogenic
Step 3: T-Cell Mediated Hepatocyte Injury
- CD4+ T cells recognise hepatocyte antigens
- Cytotoxic T-cell and NK cell-mediated destruction
- Interface hepatitis (portal-periportal inflammation)
Step 4: Fibrosis and Cirrhosis
- Chronic inflammation leads to fibrosis
- Without treatment → cirrhosis (30-50% at presentation)
Classification
| Type | Autoantibodies | Age | Features |
|---|---|---|---|
| Type 1 | ANA, SMA (smooth muscle) | Any age | Most common (80%); associated autoimmune diseases |
| Type 2 | LKM-1, LC-1 | Usually children/young adults | More severe; higher relapse rate |
Overlap Syndromes
| Syndrome | Features |
|---|---|
| AIH-PBC overlap | AIH features + AMA positive, cholestatic biochemistry |
| AIH-PSC overlap | AIH features + PSC on cholangiography (especially IBD patients) |
Symptoms
Signs
Presentations
| Presentation | Features |
|---|---|
| Chronic/Insidious | Fatigue, mild transaminitis; most common |
| Acute/Fulminant | Jaundice, coagulopathy, encephalopathy; rare (~25%) |
| Cirrhosis | 30-50% present with established cirrhosis |
| Asymptomatic | Incidental finding on LFTs or autoimmune screen |
Red Flags
[!CAUTION] Red Flags — Urgent assessment if:
- Jaundice with coagulopathy (INR greater than 1.5)
- Hepatic encephalopathy
- Rapid deterioration despite treatment
- Suspected drug-induced AIH
Structured Approach
General:
- Jaundice
- Cushingoid features (if on steroids)
- Signs of other autoimmune conditions (thyroid, vitiligo)
Abdomen:
- Hepatomegaly
- Splenomegaly
- Ascites (if decompensated)
Chronic Liver Disease Stigmata:
- Spider naevi
- Palmar erythema
- Gynaecomastia
- Testicular atrophy
- Encephalopathy
Diagnostic Criteria (Simplified IAIHG Criteria)
| Parameter | Points |
|---|---|
| ANA or SMA ≥1:40 | +1 |
| ANA or SMA ≥1:80 OR LKM-1 ≥1:40 OR SLA positive | +2 |
| IgG above ULN | +1 |
| IgG greater than 1.1x ULN | +2 |
| Liver histology compatible | +1 |
| Liver histology typical | +2 |
| Absence of viral hepatitis | +2 |
Score ≥6 = Probable AIH; ≥7 = Definite AIH
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| LFTs | Raised AST/ALT (often 5-20x ULN); ALP usually normal | Hepatocellular pattern |
| IgG | Elevated | Characteristic |
| ANA | Positive (Type 1) | Autoantibody screen |
| SMA | Positive (Type 1) | Autoantibody screen |
| LKM-1 | Positive (Type 2) | Autoantibody screen |
| SLA/LP | Positive (subset) | Highly specific |
| Viral serology | Negative | Exclude viral hepatitis |
| Ferritin, Caeruloplasmin | Normal | Exclude haemochromatosis, Wilson's |
Imaging
| Modality | Findings |
|---|---|
| Ultrasound | Hepatomegaly; may be normal; exclude obstruction |
| Fibroscan | Liver stiffness (fibrosis assessment) |
| MRCP | If PSC overlap suspected |
Liver Biopsy
Typical features:
- Interface hepatitis (lymphoplasmacytic infiltrate)
- Hepatocyte rosetting
- Plasma cell infiltration
- Bridging necrosis (in severe cases)
- Fibrosis/cirrhosis
Management Algorithm
SUSPECTED AIH
↓
┌─────────────────────────────────────────┐
│ 1. Confirm Diagnosis │
│ - Autoantibodies, IgG │
│ - Liver biopsy (if safe) │
│ - Exclude viral, drug, other causes │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ 2. Induction Therapy │
├─────────────────────────────────────────┤
│ Prednisolone 30-40mg OD │
│ PLUS Azathioprine 50mg OD │
│ (Increase azathioprine as steroids │
│ are tapered) │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ 3. Maintenance Therapy │
├─────────────────────────────────────────┤
│ Azathioprine 1-2 mg/kg (steroid-free │
│ if possible) │
│ Aim: Normal ALT/AST, normal IgG │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ 4. Consider Stopping (If) │
├─────────────────────────────────────────┤
│ - Sustained remission ≥2 years │
│ - Biopsy shows minimal/no inflammation │
│ - 50-80% relapse risk after stopping │
└─────────────────────────────────────────┘
Induction Therapy
| Drug | Dose | Notes |
|---|---|---|
| Prednisolone | 30-40 mg OD (or 1 mg/kg up to 60 mg in severe) | Taper over 6-12 weeks |
| Azathioprine | 50 mg OD initially; ↑ to 1-2 mg/kg | Check TPMT before starting |
Alternative if azathioprine intolerance:
- Mycophenolate mofetil (MMF)
- 6-mercaptopurine
Maintenance Therapy
| Strategy | Details |
|---|---|
| Azathioprine monotherapy | Goal if remission; 1-2 mg/kg |
| Low-dose pred + azathioprine | If unable to achieve steroid-free remission |
| Mycophenolate | Second-line |
Treatment Targets
| Target | Definition |
|---|---|
| Biochemical remission | Normal ALT/AST, normal IgG |
| Histological remission | Minimal inflammation on biopsy |
| Complete remission | Biochemical + histological remission |
Refractory/Relapsed Disease
| Option | Details |
|---|---|
| Increase steroids | For relapse |
| Mycophenolate | Azathioprine-intolerant or non-responders |
| Tacrolimus, Ciclosporin | Third-line |
| Biologics | Rituximab, infliximab (limited evidence) |
| Liver transplant | Decompensated cirrhosis, fulminant AIH |
Special Considerations
Pregnancy:
- Azathioprine safe to continue
- Avoid MMF (teratogenic)
- Prednisolone safe at low doses
Acute Severe/Fulminant AIH:
- High-dose steroids (IV methylprednisolone may be used)
- Early transplant assessment if no response in 7-14 days
Immediate
| Complication | Details |
|---|---|
| Fulminant liver failure | Rare; requires transplant assessment |
| Steroid side effects | Weight gain, diabetes, osteoporosis |
Late
| Complication | Details |
|---|---|
| Cirrhosis | 30-50% at presentation |
| Hepatocellular carcinoma | Increased risk in cirrhosis |
| Relapse after stopping treatment | 50-80% |
| Azathioprine toxicity | Bone marrow suppression (monitor TPMT) |
| Associated autoimmune disease | Thyroid, RA, T1DM |
Natural History
| Untreated | Treated |
|---|---|
| 5-year mortality 50% (severe) | 10-year survival greater than 90% |
| Progression to cirrhosis | 80-90% achieve remission |
Prognostic Factors
| Good Prognosis | Poor Prognosis |
|---|---|
| Early treatment | Cirrhosis at presentation |
| Complete remission | Incomplete response |
| No cirrhosis | Type 2 AIH |
| Adherence | Acute severe presentation |
Relapse
- 50-80% relapse after stopping treatment
- Most patients require lifelong maintenance
Key Guidelines
- EASL Clinical Practice Guidelines on Autoimmune Hepatitis (2015) — European Association for the Study of the Liver. J Hepatol 2015
- BSG Guidelines on Autoimmune Hepatitis — British Society of Gastroenterology.
- AASLD Practice Guidance on AIH — American Association for the Study of Liver Diseases.
Key Studies
Manns et al. (2010) — Diagnosis and management of AIH
- Comprehensive EASL position statement
- PMID: 20633946
Lohse & Mieli-Vergani (2011) — Autoimmune hepatitis
- Seminal review of pathogenesis and management
- PMID: 21296810
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Prednisolone + Azathioprine | 1b | RCTs from 1970s-80s |
| Azathioprine maintenance | 2b | Cohort studies |
| Mycophenolate for intolerance | 2b | Case series |
What is Autoimmune Hepatitis?
Autoimmune hepatitis (AIH) is a condition where your immune system mistakenly attacks your own liver, causing inflammation. Without treatment, this can lead to scarring (cirrhosis) and liver failure.
Why does it happen?
The exact cause is not known, but it involves your immune system becoming overactive against your liver cells. It tends to run in families and is associated with other autoimmune conditions.
How is it treated?
- Steroids (prednisolone): Reduce inflammation quickly.
- Azathioprine: A long-term medication that suppresses the immune system and allows steroids to be reduced.
- Monitoring: Regular blood tests to check liver function and medication side effects.
- Liver transplant: Only needed if the liver is severely damaged and doesn't respond to treatment.
What to expect
- Most people respond very well to treatment
- You will likely need medication for many years, possibly lifelong
- Regular blood tests are essential
- With treatment, you can live a normal, healthy life
When to seek help
See a doctor urgently if you have:
- Yellowing of eyes or skin (jaundice)
- Severe tiredness or confusion
- Dark urine or pale stools
- Easy bruising or bleeding
Primary Guidelines
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Autoimmune hepatitis. J Hepatol. 2015;63(4):971-1004. PMID: 26341719
Key Studies
- Manns MP, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193-213. PMID: 20513004
- Lohse AW, Mieli-Vergani G. Autoimmune hepatitis. J Hepatol. 2011;55(1):171-82. PMID: 21296810
Further Resources
- British Liver Trust: britishlivertrust.org.uk
- American Liver Foundation: liverfoundation.org
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.