Autoimmune hepatitis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Medical Therapy
Mainstay treatment of autoimmune hepatitis is pharmacotherapy. Corticosteroids alone or in combination with immunosuppressants are commonly used.
Acute Pharmacotherapies
- Pharmacologic medical therapies for Autoimmune hepatitis include Prednisone alone and combination of Azathioprine and Prednisone
According to American Association for the Study of Liver Diseases indications for immunosuppressive treatment:
Indications for Immunosuppressive Treatment | ||
---|---|---|
Absolute Indications | Relative Indications | None |
Serum AST >10 fold upper limit of normal range(ULN) | Symptoms like fatigue, arthralgia, jaundice | Asymptomatic with normal or near normal serum
AST and gamma globulin levels |
Serum AST >5 fold ULN | Serum AST and/or gamma globulin less than absolute criteria | Inactive cirrhosis or mild portal inflammation
(portal hepatitis) |
Gamma globulin level>2 fold ULN | Interface hepatitis | Severe cytopenia (white blood cell counts
<2.5 x109/L or platelet counts <50 x 109/L) |
Bridging necrosis or multiacinar
necrosis on histological examination |
Osteopenia, emotional instability, hypertension, diabetes,
or cytopenia (white blood cell counts <2.5 x109/L or platelet counts <50 x109/L) |
complete deficiency of TPMT activity
precludes treatment with azathioprine |
Incapacitating symptoms such as fatigue
and arthralgia |
Vertebral compression, psychosis, brittle diabetes,
uncontrolled hypertension, known intolerances to prednisone or azathioprine |
According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Adults with Autoimmune Hepatitis:
- Preferred regimen (1): Prednisone 60mg PO q24h for 7 days ( Preference:Cytopenia, Thiopurine methyltransferase deficiency, Pregnancy, Malignancy, Short-course (<6 months)
- Preferred regimen (2): Prednisone 40mg PO q24h for next 7 days
- Preferred regimen (3): Prednisone 30mg PO q24h for next 7 days
- Preferred regimen (4): Prednisone 30mg PO q24h for next 7 days
- Preferred regimen (5): Prednisone 20mg and below PO q24h for maintenance until endpoint
- Alternative regimen: Combination Therapy which includes Prednisone and Azathioprine
- Alternative regimen (1): Prednisone 30mg PO q24h for 7 days and Azathioprine 50mg q24h for 7 days
- Alternative regimen (2): Prednisone 20mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
- Alternative regimen (3): Prednisone 15mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
- Alternative regimen (3): Prednisone 10mg PO q24h for 7 days and Azathioprine 50mg q24h for maintenance until endpoint
Immunosuppressive Treatment Regimens for Adults in Autoimmune Hepatitis | ||||
Monotherapy
Prednisone only* (mg/day) |
Combination Therapy | |||
Weeks | Dosage | Prednisone | Azathioprine
USA (mg/day) EU (mg/kg/day) | |
First | 60 | 30 | 50 | 12 |
Second | 40 | 20 | 50 | 12 |
Third | 30 | 15 | 50 | 12 |
Fourth | 30 | 15 | 50 | 12 |
Maintenance until endpoint | 20 and below | 10 | 50 | 12 |
Reasons for Preference | Cytopenia, Thiopurine methyltransferase deficiency,
Pregnancy, Malignancy, Short-course (<6 months) |
Postmenopausal state, Brittle diabetes, Obesity, Acne,
Emotional lability, Hypertension |
Adjunctive therapies:
- Adjunctive therapy is based on medication and complication occurs due to medication
- The regular weight-bearing exercise program, vitamin D, calcium supplementation and bisphosphonates should be taken by patient who is taking corticosteroids for long-term
- Vaccination against hepatitis B virus (HBV) and hepatitis A virus (HAV) should be done as early as possible even before immunosuppression
According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Children in Autoimmune Hepatitis:
Pediatric
- Preferred regimens:
- Initial regimen (1): Prednisone 1- 2 mg/kg (upto60mg/day) PO q24h for 14 days either alone or in combination with azathioprine, 1- 2 mg/kg q24h
- Maintenance regimen (2): Prednisone taper to 0.1 -0.2 mg/kg q24h or 5 mg q24h for 6 -8 weeks
- if added initially, azathioprine at constant dose
- Continue daily prednisone dose with or without azathioprine or switch to alternate day prednisone dose adjusted in response with or without azathioprine
Immunosuppressive Treatment Regimens for Children with Autoimmune Hepatitis | ||
---|---|---|
Initial Regimen | Maintenance Regimen | Endpoint |
for two weeks either alone or in combination with azathioprine, 1- 2 mg/kg daily |
0.1 -0.2 mg/kg daily or 5 mg daily
|
|
Frequency and Nature of Side Effects Associated with Treatment in Adults with Autoimmune Hepatitis | |||
---|---|---|---|
Prednisone-Related Side Effects | Azathioprine-Related Side Effects | ||
Type | Frequency | Type | Frequency |
|
80% (after 2 years) |
|
46% (especially with cirrhosis) |
|
13% (treatment ending) |
|
6% (treatment ending) |
|
13% (treatment ending) |
|
5% |
|
Rare |
|
3% (after 10 years) |
Teratogenic during pregnancy |
Rare |
Contraindicated medications
Autoimmune hepatitis is considered an absolute contraindication to the use of the following medications:
Sample
Immunosuppressive treatment with course of action in AIH
Drug treatment Corticosteroids Azathioprine | |||||||||||||||||||||||||||||||||||
Remission Absence of symptoms Normal Serum Transaminase Normal bilirubin Normal gamma globulin level Normal histology or inactive cirrhosis | Treatment failure Worsening clinical laboratory and histological features despite compliance with therapy Development of jaundice ,ascites or hepatic encephalopathy | Incomplete response Some or no improvement in clinical, laboratory,and histological features despite compliance with therapy after 2-3 year | Drug toxicity Development of intolerable cosmetic changes, symptomatic osteopenia, emotional instability, poorly controlled hypertension, brittle diabetes or progressive cytopenia | ||||||||||||||||||||||||||||||||
Gradual withdrawal of prednisone over 6 week period Serum AST or ALT , total bilirubin, and c globulin levels determined 150 mg daily, for at least 1 monthDose reduction of prednisone by 10mg and azathioprine by 50 mg for each month of improvement until standard treatment doses are achieved | Prednisone, 60 mg daily , or prednisone, 30 mg daily,and azathioprine , 150 mg daily, for at least 1 month Dose reduction of prednisone by 10mg and azathioprine by 50 mg for each month of improvement until standard treatment doses are achieved | Reduction in doses of prednisone by 2.5 mg/month until lowest level possible (<10 mg daily) to prevent worsening of serum AST or ALT abnormalities | E04 | ||||||||||||||||||||||||||||||||
Recommendations for the Treatment of Autoimmune Hepatitis (DO NOT EDIT)
- Immunosuppressive treatment based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features
- Prednisone or prednisolone with azathioprine (adults)
- Prednisone with azathioprine or 6-mercaptopurine (children)
- Prednisone or prednisolone alone
- Monitoring for bone disease
- Adjunctive therapies for bone disease (weight-bearing exercise program, vitamin D and calcium supplementation, bisphosphonates)
- Pretreatment vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV)
- Management of treatment side effects and risks, including during pregnancy
- Alternative drug therapies for suboptimal response (cyclosporine, tacrolimus, or mycophenolate mofetil)
- Hepatic ultrasonography to detect hepatocellular carcinoma (HCC)
- Liver transplantation, management of recurrent disease after transplant with drug therapy and/or retransplantation in certain patients}}