Autoimmune Hepatitis Medication

  • Author: David C Wolf, MD, FACP, FACG, AGAF; Chief Editor: Julian Katz, MD   more...
 
Updated: Oct 28, 2011
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Treatment with corticosteroids and azathioprine is the cornerstone for achieving remission. Initiating azathioprine with prednisone at the beginning of treatment enables a faster decrease of the prednisone dose. Cyclosporine has steroid-sparing effects when administered for several months before corticosteroids and azathioprine.

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Corticosteroids

Class Summary

Rapid institution of treatment with high-dose corticosteroids may rescue patients whose disease ultimately would have progressed to either fulminant hepatic failure or cirrhosis. Treatment with corticosteroids has been shown to improve the chances for survival significantly.

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

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Prednisone

 

Prednisone is an immunosuppressant for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity. It stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.

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Prednisolone

 

Prednisolone decreases autoimmune reactions, possibly by suppressing key components of immune system. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

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Immunosuppressant agents

Class Summary

These agents inhibit immune reactions resulting from diverse stimuli. Initiating azathioprine with prednisone at the beginning of treatment enables a faster decrease of the prednisone dose. Cyclosporine has steroid-sparing effects when administered for several months before corticosteroids and azathioprine.

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Azathioprine (Imuran, Azasan)

 

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity.

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Cyclosporine (Gengraf, Sandimmune, Neoral)

 

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, graft versus host disease) for a variety of organs. The dose is based on ideal body weight.

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Contributor Information and Disclosures
Author

David C Wolf, MD, FACP, FACG, AGAF  Medical Director of Liver Transplantation, Westchester Medical Center; Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College

David C Wolf, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Unnithan V Raghuraman, MD, FACG, FACP, FRCP  Consulting Staff, Department of Gastroenterology, St John Medical Center

Unnithan V Raghuraman, MD, FACG, FACP, FRCP is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Mohammad F El-Baba, MD Associate Professor of Pediatrics, Division of Pediatric Gastroenterology, Wayne State University School of Medicine; Divison Chief of Pediatric Gastroenterology, Children's Hospital of Michigan

Mohammad F El-Baba, MD is a member of the following medical societies: American Gastroenterological Association and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Husam H Sukerek, MD Consulting Staff, Department of Gastroenterology, Sabine Medical Center

Husam H Sukerek, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Table 1. Clinical Characteristics of Autoimmune Hepatitis[13]
Clinical FeaturesType 1Type 2Type 3
Diagnostic autoantibodiesASMA



ANA



Antiactin



Anti-LKM



P-450 IID6



Synthetic core motif peptides 254-271



Soluble liver-kidney antigen



Cytokeratins 8 and 18



Age10 y-elderlyPediatric (2-14 y)



Rare in adults



Adults (30-50 y)
Women (%)788990
Concurrent immune disease (%)413458
Gamma globulin elevation++++++
Low IgA*NoOccasionalNo
HLA associationB8, DR3, DR4B14, Dr3, C4AQOUncertain
Steroid response++++++++
Progression to cirrhosis (%)458275
*Immunoglobulin A
Table 2. Indications for Treatment of Autoimmune Hepatitis in Adults
Absolute Relative
Serum AST 10-fold or more greater than the upper limit of normalSymptoms (eg, fatigue, arthralgia, jaundice)
Serum AST 5-fold or more greater than the upper limit of normal and gamma-globulin level 2-fold or more greater than normalSerum AST and/or gamma-globulin less than absolute criteria
Bridging necrosis or multiacinar necrosis on



histologic examination



Interface hepatitis
AST = aspartate aminotransferase.
Table 3. Treatment Regimens for Adults
Prednisone only (mg/d) Combination
Prednisone (mg/d)Azathioprine (mg/d)
Week 1603050
Week 2402050
Week 3301550
Week 4301550
Maintenance until



end point



201050
Reasons for PreferenceCytopenia



Thiopurine methyltransferase deficiency



Pregnancy



Malignancy



Short course (6 mo or less)



Postmenopausal state



Osteoporosis



Brittle diabetes



Obesity



Acne



Emotional lability



Hypertension



Table 4. Treatment Regimens for Children
Initial Regimen Maintenance Regimen End Point
Prednisone, 1-2 mg/kg/d (up to 60 mg/d),



for 2 weeks, either alone or in combination with azathioprine, 1-2 mg/kg/d



a. Prednisone taper over 6-8 weeks to 0.1-0.2 mg/kg daily or 5 mg daily



b. Azathioprine at constant dose if added initially



c. Continue daily prednisone dose with or without azathioprine or switch to



alternate day prednisone dose adjusted to response with or without azathioprine



a. Normal liver tests for 1-2 years during treatment



b. No flare during entire interval



c. Liver biopsy examination discloses no inflammation



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