Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

acute severe disease

1st line – high-dose corticosteroid

Back
INITIAL
|
acute severe disease
1st line – 

high-dose corticosteroid

The American Association for the Study of Liver Diseases and the European Association of the Study of the Liver define acute severe AIH as patients presenting with jaundice, international normalised ratio >1.5 to <2, no encephalopathy, and no previously recognised liver disease.[1][26]

Patients with acute severe AIH should be treated with high doses of corticosteroids as early as possible.[26] If there is a lack of improvement within 7 to 14 days, the patient should be evaluated for emergency liver transplantation.[1][26]

Primary options

methylprednisolone sodium succinate: consult specialist for guidance on dose

OR

prednisolone: 60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 60 mg orally once daily initially, taper gradually according to response

Consider – liver transplant

Back
INITIAL
|
acute severe disease
Consider – 

liver transplant

Additional treatment recommended for SOME patients in selected patient group

Patients with acute severe AIH and acute liver failure should be evaluated for liver transplant immediately.[1]

ACUTE

active disease

1st line – corticosteroid monotherapy

Back
ACUTE
|
active disease
|
expected treatment <6 months or immunosuppressant contraindication
1st line – 

corticosteroid monotherapy

All individuals with AIH should be considered as candidates for therapy except those with inactive disease based on clinical, laboratory, and histological assessment.[1]

Treatment is mandated when symptoms or disease activity are severe.

Severe disease is defined as aminotransferase levels greater than 10-fold the upper limit of normal; or 5-fold the upper limit of normal with a serum gamma-globulin level at least twice the upper limit of normal; or bridging necrosis or multi acinar necrosis on liver histology.[1][26][36]

In patients who do not satisfy criteria for severe disease, treatment must be individualised and the decision to treat or to monitor is based on the presence of symptoms (fatigue, arthralgia, jaundice); levels of serum aminotransferase, gamma-globulins, or both; and the presence of interface hepatitis on liver histology.[1]

The American Society for the Study of Liver Diseases recommends corticosteroid monotherapy as one possible initial treatment for patients with AIH who do not have acute severe hepatitis or acute liver failure.[1] Budesonide should not be used in patients who have cirrhosis.[1]

The British Society of Gastroenterology and the European Association for the Study of the Liver recommend that corticosteroid monotherapy is reserved for patients who have a contraindication to immunosuppressant therapy (e.g., cytopenia, active malignancies, or thiopurine methyltransferase deficiency), or when the presumed treatment course will be short (i.e., less than 6 months).[26][36]

Corticosteroid monotherapy is contraindicated in post-menopausal women and patients with osteoporosis, diabetes, glaucoma, cataracts, hypertension, major depression, and emotional lability.[1][26][36]

Prednisolone is an active metabolite of prednisone and either may be used; however, advanced cirrhosis can significantly impair the conversion of prednisone to prednisolone, although this impairment is usually insufficient to alter treatment response or justify the preferential administration of prednisolone.[1][41][42]

Budesonide is recommended as an alternative to prednisone or prednisolone in non-cirrhotic patients who have experienced, or are at increased risk for, severe side effects on prednisone or prednisolone (e.g., poorly controlled diabetes, osteoporosis, psychosis).[26][36] The majority of studies are favourable and report a good treatment response.[43][44][45][46]​​​[47] Budesonide monotherapy has demonstrated normalisation of transaminases, but histological responses to treatment have not been well studied thus far.[1]

Primary options

prednisolone: 40-60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 40-60 mg orally once daily initially, taper gradually according to response

Secondary options

budesonide: 9 mg orally (delayed- or extended-release) once daily

1st line – corticosteroid plus immunosuppressant

Back
ACUTE
|
active disease
|
expected treatment >6 months with no immunosuppressant contraindication
1st line – 

corticosteroid plus immunosuppressant

The American Society for the Study of Liver Diseases recommends a corticosteroid plus azathioprine as an initial treatment for patients with AIH who do not have acute severe hepatitis or acute liver failure.[1] Budesonide should not be used in patients who have cirrhosis.[1]

The British Society of Gastroenterology and the European Association for the Study of the Liver recommend a corticosteroid plus azathioprine as an initial treatment option when the presumed treatment course is >6 months, as it is considered to result in fewer adverse effects and better efficacy compared with corticosteroid monotherapy.[26][36]

Azathioprine should be started 2 weeks after corticosteroid treatment to confirm steroid responsiveness, evaluate thiopurine methyltransferase (TPMT) status, and assess treatment response by excluding the possibility of azathioprine-induced hepatitis.[1][26] Some people have a reduced TPMT activity, which mediates elimination of mercaptopurine (the active metabolite of azathioprine). Those with a lower activity of TPMT are at a higher risk of toxicity from azathioprine; therefore, it is recommended that all patients should be routinely tested for TPMT activity.[1][26][36] Azathioprine should be avoided or used at a lower dose in those with a lower activity of TPMT.

Azathioprine can be continued throughout pregnancy.[1][26] Adverse effects of azathioprine include cholestatic hepatitis, veno-occlusive disease, pancreatitis, nausea, vomiting, and bone marrow suppression.

Prednisolone is an active metabolite of prednisone and either may be used; however, advanced cirrhosis can significantly impair the conversion of prednisone to prednisolone, although this impairment is usually insufficient to alter treatment response or justify the preferential administration of prednisolone.[1][41][42]

Budesonide is recommended as an alternative option to prednisone or prednisolone in non-cirrhotic patients who have experienced severe side effects on prednisone or prednisolone (e.g., poorly controlled diabetes, osteoporosis, psychosis).[26][36]

One study of paediatric patients with AIH compared the combination of prednisone and azathioprine versus budesonide and azathioprine and found no statistically significant difference in response and adverse effects.[48] Non-significant trends were observed, including lower weight in the budesonide group and modestly improved rate of biochemical remission in the prednisone group.

Mycophenolate and ciclosporin may be considered as alternative immunosuppressants to azathioprine for patients who are intolerant to azathioprine or have a contraindication to its use.[1]

Mycophenolate combined with prednisone has been reported by systematic review evidence as superior to azathioprine with prednisone in the normalisation of alanine aminotransferase, aspartate aminotransferase, and immunoglobulin G levels and in the rate of non-response in patients with AIH.[49][50] Mycophenolate is contraindicated in pregnancy.[1]

Studies have shown that ciclosporin normalises serum transaminase levels and improves histology in AIH patients without significant adverse effects requiring cessation of therapy.[51][52] However, its high toxicity profile may limit its use due to increased risk of hypertension, renal insufficiency, hyperlipidaemia, hirsutism, opportunistic infection, and malignancy.

Primary options

prednisolone: 20-40 mg orally once daily initially, taper gradually according to response

or

prednisone: 20-40 mg orally once daily initially, taper gradually according to response

-- AND --

azathioprine: 50-150 mg/day orally given in 1-2 divided doses

Secondary options

budesonide: 9 mg orally (delayed- or extended-release) once daily

and

azathioprine: 50-150 mg/day orally given in 1-2 divided doses

OR

prednisolone: 20-40 mg orally once daily initially, taper gradually according to response

or

prednisone: 20-40 mg orally once daily initially, taper gradually according to response

-- AND --

mycophenolate mofetil: consult specialist for guidance on dose

or

ciclosporin: consult specialist for guidance on dose

inactive disease or minimally active disease with comorbidities

1st line – observation and monitoring only

Back
ACUTE
|
inactive disease or minimally active disease with comorbidities
1st line – 

observation and monitoring only

Treatment should not be initiated in patients with cirrhosis that has become inactive and can also be deferred in patients with minimally active disease who have comorbidities.[1] These patients should be followed closely with assessment at intervals of 3 to 6 months.[26]

AIH-primary biliary cirrhosis overlap syndrome

1st line – corticosteroid plus immunosuppressant or corticosteroid monotherapy

Back
ACUTE
|
AIH-primary biliary cirrhosis overlap syndrome
1st line – 

corticosteroid plus immunosuppressant or corticosteroid monotherapy

Patients with histological features of AIH but serological findings of primary biliary cirrhosis (i.e., anti-mitochondrial antibodies-positive) can rapidly progress to cirrhosis, so even asymptomatic patients should be treated.

Combination regimens of a corticosteroid and an immunosuppressant are usually preferred.[1] Patients with contraindications to immunosuppressant therapy (e.g., cytopenia, active malignancies, or thiopurine methyltransferase deficiency) are treated with corticosteroid monotherapy.[3]

Therapy should be continued until remission, treatment failure, incomplete response, or drug toxicity.[1]

Primary options

prednisolone: 20-40 mg orally once daily initially, taper gradually according to response

or

prednisone: 20-40 mg orally once daily initially, taper gradually according to response

-- AND --

azathioprine: 50-150 mg/day orally given in 1-2 divided doses

Secondary options

prednisolone: 40-60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 40-60 mg orally once daily initially, taper gradually according to response

Plus – ursodeoxycholic acid

Back
ACUTE
|
AIH-primary biliary cirrhosis overlap syndrome
Plus – 

ursodeoxycholic acid

Treatment recommended for ALL patients in selected patient group

Ursodeoxycholic acid should be given in combination with immunosuppressive therapy in patients with overlap syndrome.[1]

Primary options

ursodeoxycholic acid: 13-15 mg/kg/day orally given in 2-4 divided doses

ONGOING

inadequate response to initial therapy or single relapse: without hepatic decompensation

1st line – corticosteroid and/or immunosuppressant

Back
ONGOING
|
inadequate response to initial therapy or single relapse: without hepatic decompensation
|
no immunosuppressant contraindication
1st line – 

corticosteroid and/or immunosuppressant

Second-line therapies are used to manage treatment failure, incomplete response, and drug intolerance.[1]

Treatment failure is defined as worsening of clinical, laboratory, and histological features despite compliance with therapy.[1] An elevation of aminotransferase values by at least 67% is usually considered a sign of treatment failure, as well as development of jaundice, ascites, or hepatic encephalopathy. At least 9% of adult patients and 5% to 15% of children experience treatment failure with standard treatment schedules.

Incomplete response is defined as failure to achieve remission after 3 years of therapy, with some or no improvement in clinical, laboratory, and histological features, but with no worsening of the condition. This outcome is seen in approximately 15% of patients.[1]

Treatment intolerance indicates the inability to continue therapy due to adverse effects of the drug.[1]

The American Association for the Study of Liver Diseases (AASLD) recommends a trial of mycophenolate or tacrolimus for children and adults with AIH who have treatment failure, incomplete response, or drug intolerance to first-line agents. Based on ease of use and adverse effect profile, the AASLD suggests mycophenolate over tacrolimus as the initial second-line agent.[1] Mycophenolate is contraindicated in pregnancy.[1]

The European Association for the Study of the Liver and British Society of Gastroenterology recommend a standard approach to managing treatment failure with very high doses of a corticosteroid or a combination of a corticosteroid with azathioprine for at least 1 month.[26][36] The dose of the corticosteroid and azathioprine is reduced after each month of clinical and laboratory improvement and dose reduction is continued until conventional maintenance levels of medications are achieved.

Therapy should be continued until remission, treatment failure, incomplete response, or drug toxicity.[1]

Primary options

prednisolone: 20-40 mg orally once daily initially, taper gradually according to response

or

prednisone: 20-40 mg orally once daily initially, taper gradually according to response

-- AND --

azathioprine: 50-150 mg/day orally given in 1-2 divided doses

OR

prednisolone: 60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 60 mg orally once daily initially, taper gradually according to response

OR

mycophenolate mofetil: consult specialist for guidance on dose

OR

tacrolimus: consult specialist for guidance on dose

1st line – high-dose corticosteroid monotherapy

Back
ONGOING
|
inadequate response to initial therapy or single relapse: without hepatic decompensation
|
immunosuppressant contraindication
1st line – 

high-dose corticosteroid monotherapy

Second-line therapies are used to manage treatment failure, incomplete response, and drug intolerance.[1]

Treatment failure is defined as worsening of clinical, laboratory, and histological features despite compliance with therapy.[1] An elevation of aminotransferase values by at least 67% is usually considered a sign of treatment failure, as well as development of jaundice, ascites, or hepatic encephalopathy. At least 9% of adult patients and 5% to 15% of children experience treatment failure with standard treatment schedules.

Incomplete response is defined as failure to achieve remission after 3 years of therapy, with some or no improvement in clinical, laboratory, and histological features, but with no worsening of the condition. This outcome is seen in approximately 15% of patients.[1]

Treatment intolerance indicates the inability to continue therapy due to adverse effects of the drug.[1]

The European Association for the Study of the Liver and the British Society of Gastroenterology recommend a standard approach to managing treatment failure with very high doses of a corticosteroid for at least 1 month.[26][36] The dose of the corticosteroid is reduced after each month of clinical and laboratory improvement and dose reduction is continued until conventional maintenance levels of medications are achieved.

Therapy should be continued until remission, treatment failure, incomplete response, or drug toxicity.[1]

Primary options

prednisolone: 60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 60 mg orally once daily initially, taper gradually according to response

multiple previous relapses: without hepatic decompensation

1st line – immunosuppressant monotherapy maintenance

Back
ONGOING
|
multiple previous relapses: without hepatic decompensation
|
no immunosuppressant contraindication
1st line – 

immunosuppressant monotherapy maintenance

Relapse is defined as the exacerbation of disease activity after induction of remission and drug withdrawal, and occurs in up to 87% of adults and 80% of children.[1] It is commonly asymptomatic.

Liver tissue examination prior to drug withdrawal may help to exclude unsuspected inflammation and reduce the frequency of relapse.[1]

Patients who relapse subsequent to drug withdrawal typically respond to the original regimen.[1] A long-term maintenance regimen can be implemented when biochemical remission is achieved.

The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver state that azathioprine can be taken throughout pregnancy.[1][26]

Adverse effects of azathioprine include cholestatic hepatitis, veno-occlusive disease, pancreatitis, nausea, vomiting, and bone marrow suppression.

Primary options

azathioprine: 50-150 mg/day orally given in 1-2 divided doses

2nd line – low-dose corticosteroid plus immunosuppressant maintenance

Back
ONGOING
|
multiple previous relapses: without hepatic decompensation
|
no immunosuppressant contraindication
2nd line – 

low-dose corticosteroid plus immunosuppressant maintenance

A combination of a corticosteroid plus an immunosuppressant such as azathioprine reduces the adverse effects of corticosteroids. The low-dose corticosteroid is usually reduced monthly until the lowest dose is reached with clinical and biochemical stability.[1]

Primary options

prednisolone: 5-10 mg orally once daily

or

prednisone: 5-10 mg orally once daily

-- AND --

azathioprine: 50-150 mg/day orally given in 2 divided doses

1st line – low-dose corticosteroid maintenance

Back
ONGOING
|
multiple previous relapses: without hepatic decompensation
|
immunosuppressant contraindication
1st line – 

low-dose corticosteroid maintenance

Adults who have relapsed at least twice require long-term treatment.

Corticosteroid monotherapy is indicated in patients with contraindications to immunosuppressants (e.g., cytopenias, active malignancy, or thiopurine methyltransferase deficiency).

The major advantages of the low-dose corticosteroid monotherapy regimen are avoidance of the theoretical risks of oncogenicity and teratogenicity in fertile adults and avoidance of bone marrow suppression by immunosuppressant agents.

Patients should be monitored for adverse effects and for potential complications of corticosteroid therapy by blood pressure monitoring, routine blood tests, and eye examinations for cataracts and glaucoma; annual bone mineral densitometry of the lumbar spine and hip is also usually recommended.

Primary options

prednisolone: 5-10 mg orally once daily

OR

prednisone: 5-10 mg orally once daily

decompensated liver disease

1st line – liver transplantation evaluation

Back
ONGOING
|
decompensated liver disease
1st line – 

liver transplantation evaluation

Indicated in patients who deteriorate during or after corticosteroid treatment and in patients who are refractory to or intolerant of standard treatment and in whom end-stage liver disease develops.

Overall, liver transplantation is largely successful with 5-year survival rate of 80% to 90%.[54] Patients who receive liver transplants for AIH, however, have a greater risk of developing acute cellular and ductopenic rejection compared with patients who receive liver transplants for other conditions.[53]

Plus – high-dose corticosteroid monotherapy maintenance

Back
ONGOING
|
decompensated liver disease
Plus – 

high-dose corticosteroid monotherapy maintenance

Treatment recommended for ALL patients in selected patient group

High-dose corticosteroid monotherapy is advised before evaluation for transplantation.[1]

Primary options

prednisolone: 60 mg orally once daily initially, taper gradually according to response

OR

prednisone: 60 mg orally once daily initially, taper gradually according to response

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer