Autoimmune hepatitis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
Mainstay treatment of autoimmune hepatitis is pharmacotherapy. Corticosteroids alone or in combination with immunosuppressants are commonly used. Immunosuppressive treatment should be based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features. Regimens are different for adults and children. According to course of immunosupressants, further management is planned.
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:[1]
| 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 | |
Recommendations for the Treatment of Autoimmune Hepatitis
- Immunosuppressive treatment should be based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features.Various treatment used for adults and children:[2]
- Prednisone or prednisolone with azathioprine (adults)
- Prednisone with Mycophenolate (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.
According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Adults with Autoimmune Hepatitis
- Preferred regimen (1):[1]
- Prednisone 60mg PO q24h for 7 days ( Preference:Cytopenia, Thiopurine methyltransferase deficiency, Pregnancy, Malignancy, Short-course (<6 months)
- Tapering of prednisone should be done as follow:
- Prednisone 40mg PO q24h for next 7 days
- Prednisone 30mg PO q24h for next 7 days
- Prednisone 30mg PO q24h for next 7 days
- Prednisone 20mg and below PO q 24h for maintenance until endpoint
- Preferred regimen (2): Combination Therapy which includes Prednisone and Azathioprine:
- Tapering of prednisone should be done as follow:
- Prednisone 30mg PO q24h for 7 days and Azathioprine 50mg q24h for 7 days
- Prednisone 20mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
- Prednisone 15mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
- Prednisone 10mg PO q24h for 7 days and Azathioprine 50mg q24h for maintenance until endpoint
- Tapering of prednisone should be done as follow:
| 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, | ||
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 |
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| 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 |
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80% (after 2 years) |
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46% (especially with cirrhosis) |
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13% (treatment ending) |
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6% (treatment ending) |
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13% (treatment ending) |
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5% |
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Rare |
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3% (after 10 years) |
Teratogenic during pregnancy |
Rare | ||
Immunosuppressive treatment with course of action in AIH
| Drug treatment includes: •Corticosteroids •Azathioprine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Remission: •Absence of symptoms •Normal Serum Transaminase •Normal bilirubin •Normal gamma globulin level •Normal histology or inactive cirrhosis | Incomplete response: •Some or no improvement in clinical, laboratory,and histological features despite compliance with therapy after 2-3 year | Treatment failure: •Worsening clinical laboratory and histological features despite compliance with therapy Development of jaundice ,ascites or hepatic encephalopathy | Drug toxicity: •Development of intolerable cosmetic changes, symptomatic osteopenia, emotional instability, poorly controlled hypertension, brittle diabetes or progressive cytopenia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| •Gradual taper of prednisone over 6 week period •Serum AST orALT , total bilirubin , and gamma globulin levels every 3 weeks during tapering then every 3-6 months after stopping | •Reduction in doses of prednisone by 2.5 mg/month until lowest level possible (<10 mg daily) to prevent worsening of serum ASTor ALT abnormalities •Indefinite azathioprine therapy (2 mg/kg daily) as an alternative treatment if corticosteroid intolerance | •Prednisone, 60 mg daily , or prednisone, 30 mg daily • Azathioprine , 150 mg daily, for at least 1 month Dose reduction of prednisone by 10mg •Azathioprine by 50 mg for each month of improvement until standard treatment doses are achieved | •Reduction in dose or discontinuation of offending drug Maintenance on tolerated drug in adjusted dose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Relapse: Restart corticosteroid and Azathioprine | Inactive disease: Monitor lab test | Liver transplant | Empiric Cyclosporine3 mg BD/Tacrolimus | Empiric Mycophenolate mofetil | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Long-Term Follow up
- Perform liver function tests weekly during the first 6-8 weeks of treatment and then every 2-3 months depends upon results
- Abdominal imaging studies (e.g, ultrasound, CT, MRI) every 6 months
- Alpha-fetoprotein testing is done every 6 months
Treatment of overlap syndrome
Overlap Syndrome is diagnosed when patients who present with the features of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) along with the features of AIH, PBC-AIH or PSC-AIH[3][4][5]
| Treatment of overlap syndrome | |
|---|---|
| Types | Drugs |
| AIH-PBC | Prednisone or prednisolone
Combined with azathioprine
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| AIH-PBC | Prednisone or prednisolone in combination with azathioprine as above combined with Ursodeoxycholic acid: 13 mg/kg/day to 15 mg/kg/day |
| AIH-PSC | Prednisone or prednisolone 0.5 mg/kg/day tapered to 10 mg/day to 15 mg/day
Combined with azathioprine 50 mg/day to 75 mg/day Combined with Ursodeoxycholic acid 13 mg/kg/day to 15 mg/kg/day |
| AIH-cholestatic syndrome | Prednisone or prednisolone in combination with azathioprine as above combined with Ursodeoxycholic acid: 13 mg/kg/day to 15 mg/kg/day |
References
- ↑ 1.0 1.1 "www.aasld.org" (PDF).
- ↑ Czaja AJ (2013). "Review article: the management of autoimmune hepatitis beyond consensus guidelines". Aliment. Pharmacol. Ther. 38 (4): 343–64. doi:10.1111/apt.12381. PMID 23808490.
- ↑ Czaja AJ (2013). "Diagnosis and management of the overlap syndromes of autoimmune hepatitis". Can. J. Gastroenterol. 27 (7): 417–23. PMC 3956022. PMID 23862175.
- ↑ Al-Chalabi T, Portmann BC, Bernal W, McFarlane IG, Heneghan MA (2008). "Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival". Aliment. Pharmacol. Ther. 28 (2): 209–20. doi:10.1111/j.1365-2036.2008.03722.x. PMID 18433467.
- ↑ Chazouillères O, Wendum D, Serfaty L, Rosmorduc O, Poupon R (2006). "Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome". J. Hepatol. 44 (2): 400–6. doi:10.1016/j.jhep.2005.10.017. PMID 16356577.