eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Autoimmune Chronic Active Hepatitis: Differential Diagnoses & Workup

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

Differential Diagnoses

Other Problems to Be Considered

Differential diagnoses for autoimmune hepatitis (AIH) should include many causes of chronic liver disease, including a 1 -antitrypsin deficiency, Wilson disease, viral hepatitis, hepatotoxic drugs, and excessive alcohol consumption.

Autoimmune hepatitis must also be differentiated from autoimmune polyendocrine syndrome type I (APS-1), autoimmunity in hepatitis C virus (HCV) infection, immune-mediated drug-induced hepatitis, cryptogenic hepatitis, and overlap syndrome.

Workup

Laboratory Studies

Laboratory findings in autoimmune hepatitis (AIH) include the following:

  • Elevated serum aminotransferase levels (1.5-50 times reference values)
  • Elevated serum immunoglobulin levels, primarily immunoglobulin G (IgG)
  • Seropositive results for antinuclear antibodies (ANAs), smooth muscle antibodies (SMAs), or liver-kidney microsomal type 1 (LKM-1) or anti–liver cytosol 1 (anti-LC1) antibodies
    • SMAs are present in 90-100% of patients with autoimmune hepatitis type 1 (AIH-1). Titers range from 1:100-500,000. SMAs occur in low titers in healthy children and patients with viral hepatitis and other diseases that do not affect the liver.
    • ANAs are present in 10% of patients with AIH-1 and in association with SMAs in 40-60% of patients with AIH-1. Other autoantibodies are sometimes helpful in the diagnosis AIH-1. SLA/LP antibodies are the most specific antibody identified in AIH-1, but are only found in 10-30% of cases. Atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) are frequently present.
    • LKM-1 antibodies are present in 40-45% of patients with autoimmune hepatitis type 2 (AIH-2) and are associated with anti-LC1 antibodies in 50% of patients. Anti-LC1 antibodies occur alone in 30% of patients with AIH-2 and recognize formiminotransferase cyclodeaminase, a liver-specific 58kD metabolic enzyme.
    • Patients with AIH-2 commonly have partial immunoglobulin A (IgA) deficiency.4
  • Antiasialoglycoprotein receptor antibodies occur more often in patients with AIH-1 and may serve as a marker of inflammatory activity.
  • In 50% of patients, abnormal results on hepatic synthetic function tests include decreased albumin levels and prolonged prothrombin time.

Imaging Studies

  • When alkaline phosphatase levels are 7-8 times reference values or gamma glutamyl transferase levels are 2-3 times reference values, consider cholangiography to exclude a diagnosis of sclerosing cholangitis.

Histologic Findings

  • Histopathologic findings on liver biopsy specimens are crucial to determining the diagnosis of autoimmune hepatitis and the disease's severity. Autoimmune hepatitis is characterized by a portal mononuclear cell infiltrate that invades the limiting plate surrounding the portal triad and permeates the surrounding lobule (ie, periportal infiltrate) and beyond. A plasma cell infiltrate sometimes occurs, which, in the past, led to use of the term plasma cell hepatitis.
  • Interface hepatitis (also termed piecemeal necrosis) essentially spares the biliary tree but may involve most of the lobule.
  • Fibrosis is present in most patients with autoimmune hepatitis. Without effective therapy, fibrosis starts to connect the portal and central areas, which ultimately leads to cirrhosis.
  • Histopathologic findings in patients with autoimmune hepatitis are characteristic but nonspecific; autoimmune hepatitis has findings in common with chronic viral hepatitis, drug-associated chronic hepatitis, and several other chronic liver disorders. Multinucleated giant hepatocytes are found in 10-20% of biopsy specimens; their occurrence after the neonatal period may suggest a diagnosis of autoimmune hepatitis.

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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