📋 Key Information Summary
- Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterised by interface hepatitis, hypergammaglobulinaemia, and circulating autoantibodies; without treatment it progresses to cirrhosis and liver failure.
- Two major types: Type 1 (ANA and/or ASMA positive, anti-SLA/LP — ~85% of cases) and Type 2 (anti-LKM-1 positive — rarer, typically paediatric-onset).
- Diagnosis relies on the simplified IAIHG scoring criteria incorporating autoantibodies, IgG level, histology (interface hepatitis, plasma cell infiltrate, hepatocyte rosetting), and exclusion of viral hepatitis, drug-induced liver injury, Wilson disease, and NASH.
- Elevated serum IgG (≥1.1× ULN) is present in >80% of patients and is a hallmark biochemical feature.
- Liver biopsy remains essential for diagnosis and staging; interface hepatitis with lymphoplasmacytic infiltrate is the histological hallmark.
- Induction therapy: prednisolone 1 mg/kg/day (max 60 mg) ± azathioprine 1–2 mg/kg/day; azathioprine should be started at diagnosis unless contraindicated.
- Budesonide 3 mg TDS is an alternative corticosteroid for non-cirrhotic AIH, offering reduced systemic side-effects.
- Treatment targets: biochemical remission (normal ALT and IgG) within 6–24 months; histological remission on follow-up biopsy is the gold standard.
- Long-term maintenance: azathioprine monotherapy (1–2 mg/kg/day) after steroid taper; continue for ≥3 years minimum before considering withdrawal.
- Relapse rate on treatment withdrawal is 50–87%; indefinite maintenance therapy is recommended for most patients, especially those with cirrhosis.
- Refractory disease: mycophenolate mofetil (1–2 g/day) is second-line; tacrolimus or cyclosporin reserved for third-line or refractory cases.
- AIH-PBC overlap (Paris criteria) and AIH-PSC overlap require combination therapy with immunosuppression plus ursodeoxycholic acid.
- Pregnancy: azathioprine is generally continued; mycophenolate is teratogenic and must be stopped ≥6 weeks pre-conception; postpartum flare risk is significant.
- Aboriginal and Torres Strait Islander Australians may present later with more advanced disease; access to hepatology services in remote areas requires Telehealth coordination.
Diagnosis
Antibody Profile
Autoantibody testing is central to AIH classification. Serological markers should be interpreted in conjunction with serum IgG levels and histology.
| Antibody | AIH Type | Prevalence | Notes |
|---|---|---|---|
| ANA (antinuclear antibody) | Type 1 | ~70–80% | Titre ≥1:40 (adults) or ≥1:20 (paediatric) on IIF; also seen in other autoimmune conditions |
| ASMA (anti-smooth muscle antibody) | Type 1 | ~50–70% | Anti-actin specificity increases diagnostic confidence; may occur with or without ANA |
| Anti-SLA/LP (anti-soluble liver antigen/liver-pancreas) | Type 1 | ~10–30% | Most specific antibody for AIH; associated with more severe disease and higher relapse rate |
| Anti-LKM-1 (liver-kidney microsomal type 1) | Type 2 | ~5–10% | Targets CYP2D6; typically seen in paediatric/young female patients; may be confused with anti-LKM seen in HCV |
| Anti-LC1 (liver cytosol type 1) | Type 2 | ~30% of Type 2 | May be the sole marker; useful when LKM is weakly positive |
| pANCA (perinuclear anti-neutrophil cytoplasmic) | Type 1 | ~40–50% | Non-specific but supportive when present |
IgG elevation: Serum IgG ≥1.1× ULN is present in >80% of AIH patients. A normal IgG does not exclude AIH, but significantly elevated IgG (>1.5× ULN) substantially increases diagnostic probability and is weighted in the IAIHG scoring system.
Simplified IAIHG Diagnostic Criteria (2008)
The simplified IAIHG scoring system is preferred for clinical use (score ≥6 = probable AIH; ≥7 = definite AIH).
| Variable | Score 0 | Score 1 | Score 2 |
|---|---|---|---|
| ANA or ASMA | <1:40 | ≥1:40 | — |
| ANA or ASMA, or anti-LKM-1 | — | — | ≥1:80 |
| Anti-SLA/LP | — | — | Positive |
| IgG | Normal | >1.1× ULN | >1.46× ULN |
| Liver histology | Incompatible | Compatible | Typical |
| Absence of viral hepatitis | No | Yes | — |
Liver Biopsy — Histological Features
Liver biopsy is recommended in all patients with suspected AIH to confirm the diagnosis, assess severity, and establish baseline fibrosis staging. Key histological features include:
- Interface hepatitis (piecemeal necrosis): The histological hallmark — lymphoplasmacytic infiltration across the limiting plate into the hepatic lobule.
- Lobular hepatitis: Hepatocyte apoptosis, confluent necrosis, and dense portal/periportal mononuclear cell infiltrate.
- Plasma cell infiltrate: Prominent plasma cells within portal tracts — although plasma cells are not always present, their abundance increases diagnostic confidence.
- Hepatocyte rosetting: Arrangement of hepatocytes in a rosette pattern around a central bile canaliculus — a supportive feature of AIH.
- Emperipolesis: Active penetration of one cell by another (lymphocyte within hepatocyte) — recently described as relatively specific for AIH.
- Fibrosis/cirrhosis: Present in 25–50% at initial diagnosis; staged using METAVIR or Ishak scoring.
Exclusion of Other Aetiologies
AIH is a diagnosis of exclusion. The following must be actively excluded before confirming AIH:
- Viral hepatitis: Hepatitis A IgM, HBsAg / anti-HBc IgM, hepatitis C antibody with reflex PCR, hepatitis E IgM (particularly if travel history or animal exposure); CMV and EBV serologies if acute presentation.
- Drug-induced liver injury (DILI): Detailed medication history including over-the-counter, herbal (e.g., black cohosh, kava), and recreational drugs. Drug-induced autoimmune-like hepatitis (e.g., nitrofurantoin, minocycline, statins, infliximab) can mimic AIH and typically resolves on drug withdrawal.
- Wilson disease: Especially in patients <40 years; check ceruloplasmin, 24-hour urine copper, and hepatic copper on biopsy if low ceruloplasmin. Kayser-Fleischer rings on slit-lamp examination.
- Non-alcoholic steatohepatitis (NASH): Check metabolic risk factors (obesity, type 2 diabetes, dyslipidaemia), imaging for hepatic steatosis, and the NAS score on biopsy. Some patients have concurrent AIH and NASH.
- Alcoholic liver disease: Alcohol consumption history (>40 g/day in men, >20 g/day in women).
- Alpha-1 antitrypsin deficiency: Alpha-1 antitrypsin level and phenotype if suspected.
- Haemochromatosis: Transferrin saturation, ferritin, and HFE genotyping.
Australian laboratory note: ANA and ASMA testing by indirect immunofluorescence (IIF) on HEp-2 cells is widely available through major Australian pathology providers (Sullivan Nicolaides, Douglass Hanly Moir, Melbourne Pathology). Anti-LKM-1 and anti-SLA/LP are available as send-away tests; allow 10–14 working days. Check MBS items for autoimmune liver serology panels.
Investigations
Essential
Liver function tests (ALT, AST, ALP, GGT, bilirubin, albumin)
MBS Item 66500/66516 · Transaminase elevation typically 5–50× ULN; cholestatic pattern may suggest overlap
Essential
Serum IgG (quantitative)
MBS Item 66561 · ≥1.1× ULN in >80%; monitor during treatment for relapse detection
Essential
ANA, ASMA (IIF on HEp-2)
MBS Item 66812 · Titre ≥1:40 supports AIH; perform before immunosuppression
Available
Anti-LKM-1 (IIF on rodent liver/kidney)
Send-away · Essential if ANA/ASMA negative; distinguishes Type 2 AIH
Available
Anti-SLA/LP (ELISA)
Send-away · Most specific AIH antibody; helps when ANA/ASMA equivocal
Essential
Viral hepatitis serology (HAV IgM, HBsAg, anti-HBc IgM, anti-HCV/PCR, HEV IgM)
MBS Item 69387/69481 · Mandatory to exclude viral aetiology
Essential
Liver biopsy (percutaneous, ultrasound-guided)
MBS Item 30255 · Essential for diagnosis and fibrosis staging; perform before commencing treatment if safe
Available
Ceruloplasmin, serum copper, 24-hr urine copper
MBS Item 66524 · To exclude Wilson disease in patients <40 years
Available
FibroScan® (transient elastography)
Available at major centres · Non-invasive fibrosis assessment; does not replace biopsy for initial diagnosis
Available
MRCP (magnetic resonance cholangiopancreatography)
MBS Item 63543 · If cholestatic pattern or suspected AIH-PSC overlap
Treatment
Induction Therapy
Treatment should be initiated promptly in all patients with active AIH (elevated transaminases, elevated IgG, histological activity). The goal of induction is biochemical remission.
Prednisolone
Panafcortelone® · Generic · Corticosteroid
Adult dose
0.5–1 mg/kg/day (max 60 mg/day) PO; taper by 5–10 mg every 1–2 weeks to 20 mg, then slower taper to 5 mg/day over 6–9 months
Paediatric dose
1–2 mg/kg/day (max 40–60 mg/day) PO; taper as per adult protocol adjusted for weight
Route / Frequency
Oral, once daily (morning)
Renal adjustment
No specific dose adjustment; monitor for fluid retention
PBS status
✔ PBS General Benefit
Azathioprine
Imuran® · Thiopurine immunosuppressant
Adult dose
Maintenance dose
1–2 mg/kg/day PO; start at 50 mg/day and titrate over 2–4 weeks
Paediatric dose
1–2 mg/kg/day PO
Route / Frequency
Oral, once daily
Duration
Minimum 3 years before considering withdrawal; indefinite therapy recommended for most patients
Key safety
Check TPMT/NUDT15 genotype before commencing; myelosuppression risk with low/intermediate TPMT; FBC weekly × 4, then monthly × 3, then 3-monthly; LFTs monthly initially
Renal adjustment
Reduce dose by 25–50% if eGFR <30 mL/min; monitor FBC closely
PBS status
✔ PBS General Benefit
Budesonide
Entocort® · Corticosteroid (non-cirrhotic only)
Adult dose
3 mg TDS PO (9 mg/day); once remission is achieved, taper to 3 mg BD then 3 mg OD as maintenance
Route / Frequency
Oral, three times daily
Key limitation
Contraindicated in cirrhosis — extensive first-pass metabolism is lost with portosystemic shunting, leading to systemic steroid side-effects. Only use in non-cirrhotic patients (F0–F3).
PBS status
⚠ PBS Authority Required (for Crohn's indication; for AIH may require private prescription or Authority application)
TPMT / NUDT15 testing: Before commencing azathioprine, test thiopurine methyltransferase (TPMT) and NUDT15 genotype. Patients with very low TPMT activity (homozygous deficient) are at risk of severe pancytopenia — use azathioprine at 10% of standard dose or avoid. Patients with intermediate TPMT require dose reduction of ~50%. NUDT15 mutations are particularly relevant in East Asian populations and are increasingly tested in Australia.
Biochemical and Histological Remission Targets
Treatment response should be assessed at regular intervals against defined targets:
- Biochemical remission: Normalisation of serum AST/ALT (to ≤ ULN) and serum IgG (to ≤ ULN) — ideally achieved within 6–24 months of starting therapy.
- Complete biochemical response: Normal AST/ALT and IgG maintained for ≥6 months while on a stable maintenance regimen.
- Histological remission: Resolution of interface hepatitis on follow-up liver biopsy — the gold standard endpoint. Histological improvement lags behind biochemical improvement by 3–6 months.
- Relapse: Elevation of AST/ALT to >3× ULN after achieving remission; occurs in 50–87% after drug withdrawal.
A follow-up liver biopsy is recommended after 2–3 years of biochemical remission to confirm histological remission before considering any treatment withdrawal.
Long-Term Maintenance Therapy
After achieving biochemical and histological remission with induction therapy and steroid taper, the majority of patients require indefinite maintenance immunosuppression:
- Standard maintenance: Azathioprine monotherapy at 1–2 mg/kg/day after prednisolone has been weaned to 5 mg/day and then stopped.
- Duration: Minimum 3 years of remission before any consideration of withdrawal; many experts recommend lifelong therapy, especially in patients with cirrhosis, relapsing disease, or anti-SLA/LP positivity.
- Azathioprine intolerance: If azathioprine is not tolerated (myelosuppression, pancreatitis, hepatotoxicity, nausea), switch to mycophenolate mofetil.
Refractory or Relapsing Disease
Approximately 10–20% of patients do not achieve or maintain remission with standard prednisolone + azathioprine therapy.
Mycophenolate mofetil
CellCept® · Generic · Second-line immunosuppressant
Adult dose
500 mg BD initially, titrate to 1 g BD (max 2 g/day) PO
Paediatric dose
20–40 mg/kg/day in 2 divided doses (max 2 g/day)
Route / Frequency
Oral, twice daily
Key safety
TERATOGENIC — Category D; must stop ≥6 weeks before conception. Monitor FBC, LFTs. GI side-effects common.
Renal adjustment
Max 1 g/day if eGFR <25 mL/min; avoid in severe renal impairment
PBS status
⚠ PBS Authority Required (for transplant indication; for AIH may require private script)
Tacrolimus
Prograf® · Generic · Third-line calcineurin inhibitor
Adult dose
Start 1–2 mg BD PO; target trough 3–5 ng/mL for AIH (lower than transplant doses)
Route / Frequency
Oral, twice daily; trough levels at 10–12 hours post-dose
Key safety
Nephrotoxicity, neurotoxicity (tremor, headache), new-onset diabetes, hypertension; regular drug level monitoring essential
Renal adjustment
Use with caution; monitor serum creatinine and trough levels closely; contraindicated in severe uncontrolled renal impairment
PBS status
⚠ PBS Authority Required (for transplant indication)
Relapse Risk on Treatment Withdrawal
High relapse rate: Relapse occurs in 50–87% of patients after discontinuation of all immunosuppressive therapy. Withdrawal should only be attempted after a minimum of 3 years of sustained biochemical AND histological remission. Patients with cirrhosis, anti-SLA/LP positivity, or multiple prior relapses should continue indefinite maintenance therapy. If withdrawal is attempted, monitor AST/ALT and IgG monthly for the first 6 months, then 3-monthly for 2 years.
Risk factors for relapse after withdrawal include:
- Anti-SLA/LP antibody positivity
- Cirrhosis at diagnosis or during follow-up
- Persistent histological activity despite biochemical remission
- High IgG at time of withdrawal attempt
- Young age at diagnosis
- Type 2 AIH (anti-LKM-1 positive)
Monitoring Schedule
Weeks 1–4
FBC weekly (azathioprine); LFTs weekly; monitor for steroid side-effects (glucose, blood pressure)
Months 1–3
FBC and LFTs every 2–4 weeks; IgG monthly; azathioprine dose titration
Months 3–12
FBC, LFTs, IgG every 1–3 months; assess biochemical response
Year 2–3
LFTs and IgG every 3–6 months; consider follow-up liver biopsy at 2–3 years to assess histological remission
Ongoing (maintenance)
LFTs and IgG every 3–6 months; annual FBC; bone density (DEXA) every 2 years if prior corticosteroid use
Overlap Syndromes & Pregnancy
AIH-PBC Overlap Syndrome
AIH-PBC overlap occurs in approximately 8–10% of patients with AIH and is defined by the Paris criteria (2011), which require both sets of criteria to be met simultaneously:
AIH component (≥2 of 3)
- ALT ≥5× ULN
- IgG ≥2× ULN or ASMA positive
- Interface hepatitis on biopsy (moderate to severe)
PBC component (≥2 of 3)
- ALP ≥2× ULN
- AMA positive (titre ≥1:40)
- Florid duct lesion or ductopaenia on biopsy
Management of AIH-PBC overlap: Combination therapy with ursodeoxycholic acid (UDCA) 13–15 mg/kg/day plus standard AIH immunosuppression (prednisolone ± azathioprine). UDCA alone is insufficient as it does not control the AIH component. Monitor both cholestatic and hepatitic parameters.
Ursodeoxycholic acid (UDCA)
Ursofalk® · Generic · Bile acid
Adult dose
13–15 mg/kg/day PO in 2–3 divided doses
Route / Frequency
Oral, 2–3 times daily with food
PBS status
✔ PBS General Benefit
AIH-PSC Overlap Syndrome
AIH-PSC overlap is less common but clinically important, particularly in younger patients (paediatric and young adult). Patients present with AIH features (autoantibodies, elevated IgG, interface hepatitis) but also have cholestatic biochemistry and characteristic bile duct changes on MRCP or ERCP (beading, strictures, pruning).
- Diagnosis: MRCP is the first-line imaging investigation to evaluate for PSC-type bile duct changes. ERCP with brushings may be needed to confirm and exclude cholangiocarcinoma.
- Management: Combination of AIH immunosuppression plus UDCA 13–15 mg/kg/day. The role of UDCA in PSC remains debated, but it is commonly used in overlap syndrome to manage the cholestatic component. Immunosuppression targets the AIH component; PSC itself may not respond fully to immunosuppression.
- Surveillance: Cholangiocarcinoma risk is increased — annual MRCP or surveillance imaging; colonoscopy with biopsies every 1–3 years if concurrent IBD (which is present in ~70% of PSC patients).
Pregnancy
Pregnancy management in women with AIH requires careful pre-conception planning, multidisciplinary care (hepatologist, obstetrician, maternal-fetal medicine), and awareness of flare risk and medication teratogenicity.
Pre-conception
- Achieve stable biochemical remission for ≥6 months before conception.
- Mycophenolate mofetil is teratogenic (Category D) — must be stopped ≥6 weeks before conception; switch to azathioprine.
- Methotrexate is contraindicated — must stop 3–6 months pre-conception.
- Tacrolimus can be continued (Category C) — benefits often outweigh risks in refractory disease.
- Optimise folic acid supplementation (5 mg/day).
During pregnancy
- Azathioprine is generally continued throughout pregnancy at current dose — cessation risk of flare outweighs theoretical teratogenic risk.
- Prednisolone may be needed to manage flares — use lowest effective dose. Prednisolone is largely inactivated by placental 11β-HSD2 (except at high doses).
- Monitor LFTs and IgG monthly; more frequent monitoring if flaring.
- UDCA can be continued safely in pregnancy (for overlap syndromes).
- Budesonide should be avoided — limited safety data in pregnancy.
Postpartum
- Postpartum flare occurs in 20–40% of patients — often within the first 3 months postpartum due to immune reconstitution.
- Monitor LFTs and IgG at 2, 4, 8, and 12 weeks postpartum, then monthly for 6 months.
- Restart or escalate immunosuppression promptly if biochemical flare detected.
- Breastfeeding: azathioprine and prednisolone are generally considered compatible with breastfeeding. Low levels of 6-MMP are detected in breast milk but considered clinically insignificant.
Mycophenolate and pregnancy: Mycophenolate mofetil (MMF) is absolutely contraindicated in pregnancy (Category D). It causes a characteristic pattern of congenital malformations (microtia, cleft lip/palate, congenital heart defects) and increased miscarriage rates. Women of childbearing potential must use effective contraception while on MMF, and the drug must be discontinued at least 6 weeks before planned conception and replaced with azathioprine.
Paediatric AIH
Paediatric AIH has distinct features: higher prevalence of Type 2 (anti-LKM-1 positive), more acute/severe presentation, higher rate of cirrhosis at diagnosis, and higher relapse rates. Treatment follows the same principles but dosing is weight-based. The Bristol criteria for evaluating treatment response in paediatric AIH may be used. Long-term follow-up with transition to adult hepatology services is essential.
Aboriginal and Torres Strait Islander Health Considerations
Autoimmune hepatitis affects Aboriginal and Torres Strait Islander Australians, with evidence suggesting later presentation, higher rates of cirrhosis at diagnosis, and poorer outcomes related to healthcare access barriers. The following considerations apply:
📚 References
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