Autoimmune hepatitis: the AU general practice guide to diagnosis and treatment

Autoimmune hepatitis (AIH) is a chronic liver condition where the immune system mistakenly attacks hepatocytes — the liver’s own cells. Unlike viral hepatitis, which is caused by a specific pathogen, AIH arises because immune self-tolerance breaks down. Left untreated, progressive liver inflammation causes scarring (fibrosis) that advances to cirrhosis in 40–50% of people over years. Detected early and treated properly, about 80% of people achieve sustained remission.

It predominantly affects women (female-to-male ratio approximately 3.5:1), with two age peaks: peri-pubertal (ages 10–20) and perimenopausal (ages 45–65). Australian incidence is approximately 1–2 per 100,000 per year. About 30% of people have a concurrent autoimmune condition — most commonly thyroid disease, coeliac disease, or type 1 diabetes — so AIH rarely appears in isolation.

A. Core clinical — the AU general-practice framework

Who presents to the GP

The presentation spectrum is wide. About 25% are picked up incidentally — an unexpected ALT elevation on a routine blood test, often ordered for another reason. Another 25% present with an acute hepatitis picture: jaundice, dark urine, fatigue, right-upper-quadrant discomfort, and nausea. About 30% already have cirrhosis at diagnosis, sometimes presenting for the first time with decompensation — ascites, confusion, or variceal bleeding.

Symptoms that should prompt liver function testing and consideration of AIH include: unexplained fatigue, joint pain (small joints, often migratory), amenorrhoea in younger women, recurrent jaundice, or any liver function abnormality that does not resolve and lacks an obvious cause.

Key history to take

When AIH is possible, the history should cover:

• Drug and supplement history — nitrofurantoin, minocycline, statins, infliximab, and immune-checkpoint inhibitors (pembrolizumab, nivolumab) can all trigger an AIH-like hepatitis indistinguishable from primary AIH. Herbal supplements — kava, high-dose green tea extract, kombucha, black cohosh — are also hepatotoxic and should be asked about directly.
• Alcohol use — synergistic hepatotoxicity; document carefully.
• Autoimmune history — prior thyroid disease, coeliac disease, type 1 diabetes, rheumatoid arthritis, or inflammatory bowel disease.
• Family history — autoimmune disease in first-degree relatives.
• Pregnancy plans — relevant for drug choice.

Initial blood tests to order

eTG Complete and AASLD guidance (Mack, Hepatology 2020) both support a structured first-line workup that the GP can initiate before specialist referral:

• Liver function tests — expect hepatocellular pattern: ALT and AST typically 5–20× the upper limit of normal; ALP usually less than 2× normal. A predominantly raised ALP suggests PBC or PSC overlap.
• Albumin and INR — synthetic function markers; INR ≥1.5 is a red flag requiring urgent referral.
• Serum immunoglobulins — IgG elevated in about 85% of AIH; a normal IgG alone does not exclude the diagnosis.
• Autoantibody panel — ANA, anti-smooth muscle antibody (ASMA), anti-LKM1, anti-SLA/LP, anti-mitochondrial antibody (AMA — elevated in PBC overlap).
• Viral serology — HBsAg, anti-HBc, anti-HCV, and HEV IgM (particularly if acute presentation).
• Exclude metabolic mimics — caeruloplasmin (Wilson disease, especially under 40), alpha-1-antitrypsin level and phenotype, ferritin and transferrin saturation (haemochromatosis).
• Coeliac serology — tTG-IgA with total IgA.
• TSH — autoimmune thyroid disease coexists in 10–25%.
• Liver ultrasound — exclude biliary obstruction and focal lesions.
• Pregnancy test in women of reproductive age — essential before planning any treatment.

The simplified IAIHG diagnostic score (Hennes, Hepatology 2008) assigns points across four domains (autoantibody titres, IgG level, histology, and absence of viral hepatitis): a score of 6 is probable AIH; 7 or above is definite. This score supports diagnosis but does not replace the clinical and histological assessment.

B. Diagnosis — why liver biopsy is non-negotiable

What the biopsy shows

Liver biopsy is mandatory before starting immunosuppression in virtually all cases (AASLD 2019; EASL 2015). The hallmark findings are: interface hepatitis (inflammatory cells crossing the hepatocyte-limiting plate), a plasma-cell-predominant infiltrate, hepatocyte rosetting (liver cells clustering around a bile canaliculus), and emperipolesis (a lymphocyte lodging within a hepatocyte). These findings simultaneously confirm the diagnosis, grade the severity of inflammation, and stage fibrosis — all of which shape treatment intensity.

If coagulopathy makes a percutaneous biopsy unsafe, a transjugular approach via interventional radiology is an alternative. FibroScan (transient elastography) can give a non-invasive fibrosis estimate but is less reliable during active inflammation (flares falsely elevate readings), and it does not replace the histological diagnosis.

Practical pitfall: drugs and supplements

Drug-induced AIH-like hepatitis — most commonly from nitrofurantoin, minocycline, or immune-checkpoint inhibitors — is serologically and histologically indistinguishable from primary AIH. The clue is a temporal link to drug exposure and, sometimes, resolution after withdrawal. A thorough medication and supplement history, cross-checked against the Australian Medicines Handbook, is non-negotiable before labelling a case as primary AIH.

C. Treatment — immunosuppression and what to monitor

Standard first-line regimen

Treatment follows a two-phase approach: induction then maintenance. The combination of prednisolone and azathioprine achieves biochemical remission in approximately 80% of people at 18 months and is preferred over prednisolone alone because the combination allows a lower cumulative steroid dose (Czaja, Am J Gastroenterol 2002).

Induction typically starts with prednisolone 0.5–1 mg/kg/day (usually 40–60 mg daily). After approximately 2 weeks — once the TPMT result is available — azathioprine 1–2 mg/kg/day is added. The TPMT gene test or enzyme activity check is essential: a small proportion of people have a variant causing profound bone-marrow suppression from standard azathioprine doses.

For people with non-cirrhotic, non-severe AIH, budesonide 9 mg/day combined with azathioprine achieves similar remission rates as prednisolone with significantly fewer steroid-related side effects (moon face, weight gain, bone loss, glucose dysregulation), because budesonide has extensive first-pass hepatic metabolism (Manns, Gastroenterology 2010). Budesonide must be avoided in cirrhosis — portosystemic shunting removes the first-pass advantage and raises systemic exposure.

Maintenance and treat-to-target

The treatment target is: normal ALT, normal IgG, and — ideally — histological remission on repeat biopsy. Normal biochemistry alone is an inadequate endpoint because some people with biochemically normal results still have active histological inflammation that predicts relapse (AASLD 2019).

Long-term maintenance is azathioprine 1–2 mg/kg/day after steroid taper. Monitoring during stable maintenance: full blood count and liver function tests every 3 months; IgG every 6 months. Annual review should include lipids, HbA1c (steroid-related), blood pressure, weight, and a skin check (azathioprine raises non-melanoma skin cancer risk — sun protection is important year-round).

When first-line fails

Mycophenolate mofetil (MMF) 1–1.5 g twice daily is standard second-line for azathioprine intolerance or non-response, achieving biochemical remission in about 60% of this group. MMF is teratogenic — it must be stopped at least 6 weeks before conception and is contraindicated during pregnancy and breastfeeding. Beyond MMF, tacrolimus and ciclosporin are third-line specialist options.

D. Australian operations

Referral and MBS items

All suspected AIH cases should be referred to hepatology or gastroenterology. Diagnosis (biopsy), induction planning, and first-line treatment belong with a specialist. Long-term maintenance monitoring can then be shared between the GP and specialist.

Urgency of referral:

• Routine: any new suspected AIH with ALT elevation, autoantibodies, and elevated IgG.
• Semi-urgent (within days): ALT more than 5× normal, jaundice without coagulopathy, or suspected overlap syndrome.
• Urgent/ED: INR ≥1.5, bilirubin ≥10× normal, any encephalopathy, ascites, or suspected variceal bleeding.

Standard Medicare items for GP-initiated workup include LFTs, FBC, immunoglobulins, autoantibody panel, viral hepatitis serology, ferritin, caeruloplasmin, and coeliac serology under routine pathology episode-of-care. Liver ultrasound is billed as MBS item 55054. Specialist consultation under items 132 (initial) and 133 (subsequent). Liver biopsy (percutaneous) under item 30419.

The GP Chronic Condition Management Plan (GPCCMP, items 965 and 967 from 1 July 2025) is applicable for AIH — it is a chronic, complex condition often involving hepatology, dietitian, endocrinology (steroid-induced diabetes, osteoporosis), and sometimes psychology.

PBS medications

Prednisolone (5 mg and 25 mg tablets) and azathioprine (50 mg tablets) are both PBS-listed on the general schedule. Budesonide oral (Entocort) is not PBS-listed for AIH — it is usually written as a private prescription. Mycophenolate mofetil is PBS-listed for organ transplant indications only; for AIH it requires a private prescription or specialist authority application. The PBS and AMH are the authoritative AU references for current listings.

Vaccinations and bone protection

Before starting immunosuppression (if time permits), offer hepatitis A, hepatitis B, pneumococcal, influenza, COVID-19, and — importantly — MMR and VZV (measles-mumps-rubella and varicella) vaccines. Live vaccines cannot be given once immunosuppression begins. The Australian Immunisation Handbook outlines immunocompromised schedules. Start bone protection from day one of steroids: calcium, vitamin D, weight-bearing exercise, and a baseline DEXA scan.

E. Special populations

Pregnancy. Plan carefully. Azathioprine and prednisolone are considered compatible with pregnancy and breastfeeding. MMF must stop at least 6 weeks before conception. Disease flares are more common in the third trimester and postpartum — monitor more frequently. Pre-conception hepatology review is essential.

Adolescents. Type 2 AIH (anti-LKM1 positive) is more common in children and adolescents and is often more aggressive, with a higher risk of cirrhosis at presentation and more frequent relapses on withdrawal. Paediatric hepatology shared care is the preferred model.

Older adults. Lower starting steroid doses are used to minimise side effects. Aggressive monitoring of blood glucose, blood pressure, weight, bone density, and skin is needed given that steroid side effects accumulate with age.

Cirrhotic patients. HCC surveillance with 6-monthly liver ultrasound ± AFP is required. Varices screening is performed endoscopically. Budesonide is avoided. Transplant assessment should be discussed early with decompensating cirrhosis.

People from ATSI communities. Higher rates of hepatitis B and C coexist — thorough exclusion of viral aetiology is essential before treatment. Telehealth-supported co-management with the Aboriginal Community Controlled Health Organisation may support adherence to monitoring.

When to escalate

Refer or escalate urgently when:

• INR ≥1.5, bilirubin ≥10× normal, or any hepatic encephalopathy (confusion, asterixis) — this is acute-severe AIH, high mortality, immediate transfer to a transplant-capable centre.
• Suspected acute liver failure (INR ≥1.5 with encephalopathy) — list for transplant consideration.
• New ascites or suspected variceal haemorrhage.
• Inadequate response after 3 months of appropriate first-line immunosuppression.
• Serious infection while on immunosuppression — fever, persistent cough, unusual skin lesion, or atypical symptoms.
• Any new focal liver lesion on imaging (HCC surveillance).

What this article is and is not

This is general health information drawn from current Australian gastroenterology and hepatology guidelines — Therapeutic Guidelines, Australian Medicines Handbook, GESA, AASLD 2019, and EASL 2015. It does not constitute personal medical advice and does not create a doctor–patient relationship. Specific treatment decisions — including drug choices, doses, and biopsy timing — are made between you and your own treating clinicians.

For Australian consumer information: Liver Foundation Australia, HealthDirect — autoimmune hepatitis, Better Health Channel.

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Sources cited

1. RACGP — Clinical resources for gastroenterology
2. Therapeutic Guidelines (eTG) — Autoimmune hepatitis
3. Australian Medicines Handbook
4. GESA — Gastroenterological Society of Australia
5. Australian Immunisation Handbook
6. Liver Foundation Australia
7. HealthDirect — autoimmune hepatitis
8. Better Health Channel — liver disease
9. PBS — Pharmaceutical Benefits Scheme
10. AASLD 2019 — Mack, Hepatology 2020
11. EASL 2015 — Autoimmune hepatitis guidelines
12. Hennes — Simplified criteria for AIH diagnosis (Hepatology 2008)
13. Manns — Budesonide vs prednisone in AIH (Gastroenterology 2010)
14. Czaja — Prednisone vs prednisone-azathioprine combination for AIH (Am J Gastroenterol 2002)