eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Autoimmune Chronic Active Hepatitis: Treatment & Medication

Author: Husam H Sukerek, MD, Consulting Staff, Department of Gastroenterology, Sabine Medical Center
Coauthor(s): Mohammad F El-Baba, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Wayne State University School of Medicine; Divison Chief of Pediatric Gastroenterology, Children's Hospital of Michigan
Contributor Information and Disclosures

Updated: Dec 1, 2008

Treatment

Medical Care

Patients with autoimmune hepatitis (AIH) usually respond to immunosuppressive therapy.

  • The treatment of choice is corticosteroid administration, either alone or in combination with azathioprine.
    • Initiate prednisolone at 2 mg/kg/d (not to exceed 60 mg/d). Taper over 4-8 weeks, if testing of transaminase levels demonstrates gradual improvement, then administer the minimum maintenance dose required to sustain reference levels of liver enzymes.
    • Frequently check liver enzyme levels during the initial period of treatment (ie, first 6-8 wk). Liver enzyme levels are usually checked weekly to fine tune the treatment and avoid adverse effects from the steroids.
    • Liver enzymes levels may require several months to return to reference range values. In patients with autoimmune hepatitis type 1 (AIH-1), transaminase levels took a median of 0.5 years (range, 0.2-7 y) to return to reference values; in patients with autoimmune hepatitis type 2 (AIH-2), transaminase levels took a median of 0.8 years (range, 0.02-3.2 y) to return to reference values. If liver enzyme levels do not return to reference values during the first 4-8 weeks of treatment or if improvement requires high doses of steroids, initiate azathioprine administration at 0.5 mg/kg/d and gradually increase to 2 mg/kg/d until transaminase levels return to reference values. Some authors recommend starting azathioprine with prednisone at disease onset.
  • A few reports in the adult and pediatric literature have mentioned the successful use of cyclosporine to avoid high steroid doses. Cyclosporine was administered for 6 months alone, followed by combined low doses of prednisone and azathioprine for 1 month, then cyclosporine was discontinued. According to a 1999 report by Alvarez et al, cyclosporine administration induced biochemical remission of the hepatic inflammatory process in children with AIH while causing few and well-tolerated adverse effects.6 In 2004, Sciveres et al reported that cyclosporine may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy.7
  • Limited data are available regarding the use of tacrolimus, methotrexate, mycophenolate mofetil, and others.

Surgical Care

Approximately 10-20% of patients require liver transplantation. Indications for liver transplantation include the following:

  • Fulminant hepatic failure
  • Complications of cirrhosis
  • Failure of medical therapy

Medication

Treatment with corticosteroids and azathioprine is the cornerstone for achieving remission.

Glucocorticoids

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


Prednisone (Deltasone, Meticorten, Orasone)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

5-60 mg/d PO

Pediatric

2 mg/kg/d PO for 4-8 wk until liver enzyme levels return to reference values; not to exceed 60 mg/d; taper to lowest possible dose required to maintain remission

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, carbamazepine, or rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue, fungal, or tubercular skin infections; GI tract disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur


Prednisolone (Pediapred, Delta-Cortef)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

5-60 mg/d PO/IV/IM

Pediatric

2 mg/kg/d PO for 4-8 wk until liver enzyme levels return to reference values; not to exceed 60 mg/d; taper to lowest possible dose required to maintain remission

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer disease, diabetes, and myasthenia gravis

Immunosuppressive agents

Recent data suggest initiating azathioprine with prednisone at the beginning of treatment. This enables a faster decrease of the prednisone dose. Other studies have shown that cyclosporine has steroid-sparing effects when administered for several months before corticosteroids and azathioprine.


Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Adult

1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d

Pediatric

1.5-2 mg/kg/d PO

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Documented hypersensitivity; low levels of serum thiopurine methyltransferase

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check thiopurine S-methyltransferase level before therapy, low levels may accumulate thioguanine nucleotides in bone marrow and develop hematopoietic toxicity; monitor liver, renal, and hematologic function; pancreatitis rarely associated


Cyclosporine (Sandimmune, Neoral)

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. Dose is based on ideal body weight.

Adult

4-6 mg/kg/d PO divided bid

Pediatric

4 mg/kg/d PO divided tid

Substrate of CYP3A4, therefore, caution with coadministration of inducers or inhibitors of the isoenzyme; carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UV-B radiation in psoriasis because administration may increase risk of cancer

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN and serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV use only for patients who cannot take oral medications; monitor cyclosporine levels to adjust dose and avoid nephrotoxicity, maintain level at approximately 250 ng/mL in the first 3 mo and 200 ng/mL for the following 3 mo

More on Autoimmune Chronic Active Hepatitis

Overview: Autoimmune Chronic Active Hepatitis
Differential Diagnoses & Workup: Autoimmune Chronic Active Hepatitis
Treatment & Medication: Autoimmune Chronic Active Hepatitis
Follow-up: Autoimmune Chronic Active Hepatitis
References
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References

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Further Reading

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Keywords

autoimmune chronic active hepatitis, lupoid hepatitis, plasma cell hepatitis, autoimmune hepatitis, pediatric hepatitis, liver disease in children, AIH, AIH-1, AIH-2, necroinflammatory hepatitis, autoimmune disease, juvenile cirrhosis, acute hepatitis, rubella, Epstein-Barr, hepatitis A, hepatitis B, hepatitis C, hepatitis C virus, HCV, fulminant hepatic failure, autoimmune thyroiditis, celiac disease, inflammatory bowel disease, diabetes mellitus, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, APECED,  hepatomegaly, splenomegaly, ascites, ulcerative colitis, sclerosing cholangitis, arthritis, vasculitis, glomerulonephritis

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Contributor Information and Disclosures

Author

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.

Coauthor(s)

Mohammad F El-Baba, MD, Assistant 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.

Medical Editor

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

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

Chief Editor

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.

 
 
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