Autoimmune hepatitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

AIH arises from loss of immune tolerance to hepatocytes in a genetically susceptible person. It affects women more often but occurs in every sex and ethnicity, and association with autoimmune thyroid disease, coeliac disease, type 1 diabetes, inflammatory bowel disease and vitiligo is common. Presentation may be fatigue, arthralgia, amenorrhoea, pruritus, jaundice or an asymptomatic hepatitic blood pattern. Established cirrhosis can be present despite a short symptom history, so symptom duration does not stage the liver.

No single marker proves the diagnosis. Aminotransferases can be markedly raised while alkaline phosphatase is less prominent, but mixed or cholestatic patterns prompt evaluation for PBC, PSC, biliary obstruction and drug injury. Serum IgG is often high; ANA and SMA titres add evidence but occur in other liver diseases. Anti-SLA is relatively specific when available. Viral hepatitis serology, medicine and supplement history, alcohol and metabolic testing are essential. Wilson disease is especially important in a young person with severe hepatitis. Liver biopsy supports diagnosis, grades activity, stages fibrosis and may uncover an overlap pattern.

Untreated active AIH can progress to cirrhosis and death, whereas appropriate immunosuppression usually achieves remission. Treatment has two phases: corticosteroid-led control of inflammation and durable steroid-sparing maintenance. Response should be visible within weeks; biochemical non-response demands checks of adherence, diagnosis, infection, dose and competing injury rather than reflexive escalation. Acute severe disease needs frequent reassessment because corticosteroids may help selected patients but should not postpone transplantation when encephalopathy or worsening synthetic failure develops.

Key points

Autoimmune hepatitis is an immune-mediated necroinflammatory liver disease that can present at any age, from incidental aminotransferase elevation to acute liver failure.
The diagnosis combines biochemistry, immunoglobulin G, autoantibodies, compatible histology and deliberate exclusion of viral, metabolic, obstructive and drug-related liver injury.
Antinuclear and smooth-muscle antibodies support type 1 disease; anti-LKM1, anti-LC1 or anti-SLA can help in selected seronegative or atypical presentations.
Normal IgG or negative conventional antibodies does not exclude acute autoimmune hepatitis, especially early in a severe presentation.
Interface hepatitis with lymphoplasmacytic inflammation is characteristic but not pathognomonic; biopsy interpretation must include the clinical differential and recent medicines.
The simplified AIH score organises evidence but should not replace expert judgement, particularly in acute, cholestatic, paediatric or overlap phenotypes.
Prednisolone is standard induction; the 2025 BSG guideline recommends approximately 0.5 mg/kg once each morning and usually no more than 40 mg daily for typical adults.
Azathioprine provides steroid-sparing maintenance after thiopurine-methyltransferase assessment and requires structured blood-count and liver-test monitoring.
Biochemical remission means normal aminotransferases and IgG, not merely improvement; persistent low-grade activity can continue fibrosis silently.
Stopping treatment is considered only after sustained complete remission and specialist review because relapse is common and some patients need lifelong immunosuppression.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Genetic immune susceptibility

Autoimmune hepatitis arises in genetically susceptible people through loss of immune tolerance to hepatocyte antigens, with a strong female predominance.

Environmental triggers

Infections and other environmental exposures may trigger disease in susceptible individuals, although a specific precipitant is usually not demonstrable.

Drug-induced autoimmune-like injury

Selected medicines can produce an autoimmune-like hepatitis phenotype; exposure timing and behaviour after withdrawal help distinguish it from persistent idiopathic disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Loss of hepatic tolerance
Autoreactive lymphocytes escape regulation and target hepatocyte antigens, accompanied by characteristic immunoglobulin and autoantibody patterns in active disease.
2
Interface inflammation
Lymphoplasmacytic inflammation crosses the limiting plate and causes hepatocyte injury, sometimes progressing rapidly despite non-specific symptoms.
3
Fibrosis or acute failure
Untreated inflammation drives bridging fibrosis and cirrhosis, while fulminant immune injury can abruptly impair synthesis and cause encephalopathy.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Incidental hepatitic pattern

Alanine or aspartate aminotransferase elevation, raised IgG and compatible autoantibodies are found in an otherwise well person, sometimes with another autoimmune disorder.

Symptomatic inflammatory hepatitisRed flag

Fatigue, anorexia, nausea, right-upper-quadrant discomfort, dark urine, jaundice and arthralgia accompany a predominantly hepatocellular biochemical injury.

Acute severe presentationRed flag

New jaundice with INR prolongation but no encephalopathy requires urgent inpatient hepatology assessment and close trajectory monitoring.

Acute liver failureRed flag

Coagulopathy plus any altered behaviour, sleep reversal, confusion, asterixis or coma in a person without known cirrhosis needs immediate transplant-centre discussion.

Established cirrhosisRed flag

Splenomegaly, thrombocytopenia, ascites, varices, muscle loss or a nodular liver may reveal longstanding disease despite modest current aminotransferases.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Liver biochemical and synthetic profileFirst step
Why
Define injury pattern, severity and trajectory.
Interpretation and limitations
Trend ALT, AST, ALP, bilirubin, albumin, INR and glucose rather than interpreting one sample. INR rise, hypoglycaemia or bilirubin progression signals reduced functional reserve and greater urgency.
02
Serum immunoglobulin G
Why
Provide diagnostic and response evidence for immune-mediated hepatitis.
Interpretation and limitations
Elevation above the laboratory upper limit supports AIH and should normalise with complete response. A normal value, particularly in acute disease, cannot safely exclude the diagnosis.
03
Autoantibody panel
Why
Identify a compatible autoimmune serological pattern.
Interpretation and limitations
Request ANA, SMA and anti-LKM1 with laboratory titres or patterns; add anti-SLA or anti-LC1 when the initial screen is negative or phenotype atypical. Low titres can be non-specific.
04
Aetiology exclusion screen
Why
Identify viral, metabolic, toxic and biliary alternatives before immunosuppression.
Interpretation and limitations
Use hepatitis testing, iron indices, caeruloplasmin and copper studies where age or severity warrants, alpha-1 antitrypsin assessment, ultrasound and a precise prescribed, over-the-counter and supplement timeline.
05
Liver ultrasonography with portal assessment
Why
Exclude obstruction, assess morphology and identify portal-hypertension or focal complications.
Interpretation and limitations
A normal ultrasound does not exclude hepatitis or fibrosis. Dilated ducts, vascular thrombosis, splenomegaly, ascites or a focal lesion changes the diagnostic and urgency pathway.
06
Liver biopsy
Why
Confirm compatible inflammation, stage fibrosis and identify overlap or another injury.
Interpretation and limitations
Interface activity, hepatocyte rosettes and plasma cells support AIH but are not unique. Choose percutaneous or transvenous access from ascites, platelets, haemostasis and local expertise; do not delay transplant referral for biopsy.
07
Thiopurine methyltransferase assessment
Why
Reduce severe myelotoxicity risk before azathioprine.
Interpretation and limitations
Absent activity generally precludes standard azathioprine and reduced activity requires specialist adjustment. Normal activity does not eliminate later marrow or liver toxicity, so blood monitoring remains mandatory.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Drug-induced liver injury

A plausible medicine latency, improvement after withdrawal and absent relapse off immunosuppression favour autoimmune-like DILI; autoantibodies alone do not settle causation.

Viral hepatitis

Targeted viral serology and nucleic-acid testing identify infection that can mimic hepatocellular inflammation and may worsen under immunosuppression.

Cholestatic overlap disease

Prominent cholestasis, antimitochondrial antibodies or characteristic bile-duct imaging suggests PBC, PSC or an overlap phenotype requiring specialist interpretation.

Additional chapter-specific clues

Overlap or mimic

Prominent alkaline phosphatase elevation, inflammatory bowel disease, biliary stricturing, antimitochondrial antibodies or poor expected response suggests PSC, PBC, drug injury or another combined phenotype.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Diagnostic work-upBuild a defensible AIH diagnosisFirst stepA hepatitic blood pattern, raised IgG or unexplained inflammatory hepatitis raises autoimmune hepatitis.

1Assess jaundice, encephalopathy, INR, glucose and haemodynamics first and admit urgently when synthetic function is impaired.
2Obtain IgG and a structured autoantibody panel while excluding viral hepatitis, Wilson disease where relevant, biliary obstruction, alcohol and medicine or supplement injury.
3Arrange liver biopsy through the safest route when it will confirm activity, fibrosis or overlap and does not delay emergency care.
4Integrate findings with an AIH score as support, then have a hepatologist resolve seronegative, cholestatic, acute severe and drug-triggered uncertainty.

02InductionSuppress active inflammation and measure responseActive AIH is sufficiently supported and treatment benefit exceeds immunosuppressive risk.

1Screen for infection, pregnancy, diabetes, bone risk and vaccination needs, record baseline blood counts and discuss steroid adverse effects and sick-day contact routes.
2Start prednisolone using the 2025 BSG weight-based approach and add azathioprine at the specialist-selected time after TPMT and clinical suitability review.
3Review aminotransferases, bilirubin, IgG, INR, symptoms and drug toxicity frequently, tapering corticosteroid only as biochemical control is established.
4Second lineIf response is inadequate, verify adherence and diagnosis, examine drug metabolites or toxicity where appropriate and seek expert second-line advice rather than simply increasing every medicine.

03Acute severe diseaseProtect the transplant windowJaundice and coagulopathy indicate acute severe AIH or encephalopathy marks acute liver failure.

1Admit to a liver-capable unit, culture and image for infection, exclude viral, vascular, toxic and Wilson causes and discuss immediately with a transplant centre.
2Consider a closely supervised corticosteroid trial only after specialist assessment, with explicit early biochemical and clinical stopping criteria.
3Track INR, bilirubin, glucose, lactate, creatinine and mental state at least daily or more often according to instability.
4Transfer for transplantation assessment without delay when encephalopathy, worsening INR, rising bilirubin, metabolic failure or non-response indicates a closing rescue window.

04MaintenanceSustain complete biochemical remissionAminotransferases and IgG normalise and corticosteroid taper is under way.

1Continue the lowest effective steroid-sparing regimen with scheduled blood-count, liver-test, infection, skin and cervical-screening safeguards.
2Manage bone health, metabolic steroid effects and vaccinations, and provide pregnancy planning before changing effective therapy.
3Consider withdrawal only after prolonged complete biochemical remission, usually at least two years, with expert appraisal of relapse and fibrosis risk.
4After any withdrawal, monitor closely for biochemical relapse and restart treatment promptly when recurrence is confirmed rather than awaiting symptoms.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Rapidly suppresses immune-mediated hepatocyte inflammation and induces biochemical remission.

Prednisolone

For usual adult induction, the 2025 BSG guideline recommends approximately 0.5 mg/kg by mouth once each morning and not usually more than 40 mg daily, followed by response-led tapering under hepatology supervision.

Exclude or treat significant infection and monitor glucose, blood pressure, mood, sleep, eye and bone risks. Acute severe disease needs transplant-centre oversight; do not taper abruptly after sustained exposure or use response to steroids as retrospective proof of diagnosis.

Steroid-sparing maintenance immunosuppression that supports durable normalisation of aminotransferases and IgG.

Azathioprine

A hepatologist selects the weight-based dose within current BSG and BNF guidance after TPMT assessment, commonly introducing it during induction and titrating to response, tolerability and blood monitoring rather than using a fixed universal regimen.

Check full blood count and liver tests frequently during initiation, then at protocol intervals. Avoid standard use with absent TPMT activity; review pancreatitis, cytopenia, infection, malignancy, allopurinol or febuxostat interaction, vaccination and pregnancy issues with specialists.

Alternative corticosteroid induction or maintenance component in carefully selected patients without portal-systemic shunting.

Budesonide

Use only through a specialist AIH pathway at the current BNF regimen for selected non-cirrhotic adults when a lower systemic steroid burden is important; it is not an emergency substitute for prednisolone.

Do not use in cirrhosis or acute severe AIH because first-pass handling is unreliable and thrombotic or systemic toxicity may increase. Review CYP3A interactions, adrenal suppression and failure to achieve complete biochemical response.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute liver failure

Severe presentation can cause rapidly rising coagulopathy, jaundice, hypoglycaemia and encephalopathy, requiring early transplant-centre discussion without delay.

Cirrhosis and portal hypertension

Persistent or relapsing inflammation produces advanced fibrosis, ascites, varices and hepatocellular carcinoma risk even after biochemical improvement.

Immunosuppression toxicity

Corticosteroids and steroid-sparing agents can cause infection, metabolic, bone, haematological or reproductive harm, making structured monitoring integral to care.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During induction trend ALT, AST, bilirubin, IgG, albumin and INR at intervals matched to severity, with much closer review for jaundice or impaired synthesis.
Check full blood count and liver tests according to the thiopurine initiation schedule and urgently for fever, bruising, mouth ulcers, abdominal pain or new jaundice.
Record weight, blood pressure, glucose, mood, sleep, infection and bone protection while corticosteroid exposure remains clinically important.
Define remission only when aminotransferases and IgG are normal; document adherence and investigate persistent activity rather than accepting partial improvement.
Stage cirrhosis and provide six-monthly hepatocellular carcinoma surveillance, portal-hypertension care and transplant consideration where indicated.
After treatment withdrawal use frequent biochemical monitoring in the first year and ongoing lifelong review because relapse may precede symptoms.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Seronegativity is not immunity

Conventional antibodies and IgG can be normal in acute disease; severe compatible hepatitis still deserves expert biopsy and exclusion work-up.

Scores organise, they do not judge

The simplified score performs best in typical chronic presentations and can under-call acute, overlap or treated disease.

Biochemical silence matters

A patient may feel well while low-grade aminotransferase and IgG elevation continues histological damage and fibrosis.

Steroid response is not specific

Drug injury and other inflammatory conditions may improve transiently, so a response cannot repair an incomplete initial diagnosis.

Transplant referral runs in parallel

In acute severe AIH, a trial of corticosteroid and transplant assessment are complementary; serial deterioration must not be hidden by therapeutic optimism.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing AIH from a positive antinuclear antibody alone without excluding common and dangerous alternative causes.
02
Rejecting acute autoimmune hepatitis because IgG or conventional autoantibodies are initially normal.
03
Starting azathioprine without TPMT assessment, baseline blood counts and an explicit monitoring schedule.
04
Tapering corticosteroid according to symptoms while aminotransferases and IgG remain above normal.
05
Using budesonide in cirrhosis or acute severe hepatitis despite altered first-pass metabolism and insufficient emergency evidence.
06
Delaying transplant-centre contact until a corticosteroid trial has definitively failed in a deteriorating patient.