eMedicine Specialties > Gastroenterology > Liver

Isoniazid Hepatotoxicity: Differential Diagnoses & Workup

Author: Richard A Weisiger, MD, PhD, Director, GI and Liver Faculty Practice, Professor, Department of Internal Medicine, University of California San Francisco
Contributor Information and Disclosures

Updated: Jun 21, 2007

Differential Diagnoses

Alcoholic Hepatitis
Fatty Liver
Hemochromatosis
Hepatitis, Viral
Toxicity, Mushroom
Wilson Disease

Other Problems to Be Considered

Toxicity from other drugs

Exclude exogenous hepatotoxins, such as chlorinated hydrocarbons, poisonous mushrooms, and halothane (where it is still used), by careful review of the patient's history.

Other drugs commonly used with isoniazid that also may produce hepatotoxicity include protease inhibitors (for treating HIV) and pyrazinamide.

Workup

Laboratory Studies

  • Diagnosis requires exclusion of other causes of hepatitis.

    • Serum transaminases (AST, ALT): Transaminase values that are elevated less than 3-fold in a patient who is asymptomatic allow cautious continued administration of isoniazid. However, additional testing to exclude other causes of hepatitis is usually indicated. Transaminase elevations greater than this level usually require discontinuation of isoniazid and any other potentially hepatotoxic drugs.
    • Viral serologies: Hepatitis A may be excluded by a negative anti-HAV (hepatitis A virus) immunoglobulin M (IgM). Hepatitis C is excluded by a negative anti-HCV (hepatitis C virus) antibody; however, this test occasionally may remain negative for several weeks after onset of hepatitis C. Hepatitis B may be excluded either by a negative hepatitis B surface antigen (HBsAg) or by a negative antibody to hepatitis B core antigen (anti-HBc). Testing for viral DNA or RNA also may be used, but it is more expensive.
    • Exclude other toxins: In patients with a compatible history, blood or urine levels of other potential hepatotoxins (eg, acetaminophen, ethanol) may be useful.
    • Prothrombin time: The international normalized ratio (INR) usually is normal in early and mild cases. Significant elevation of the INR that does not respond to parenteral vitamin K is a grave sign that should prompt hospitalization and consultation with a transplant hepatologist.
    • Serum iron studies: High transferrin saturations associated with high ferritin levels suggest hemochromatosis, which often presents with transaminase abnormalities. However, ferritin is an acute phase reactant that often is elevated in other types of hepatitis. Thus, the presence of high ferritin levels does not suggest hemochromatosis, unless the iron saturation also is high. Genetic testing for hemochromatosis may be useful in these patients.
    • Serum ceruloplasmin: In younger persons, exclude Wilson disease, especially if any neuropsychiatric components exist.

Imaging Studies

  • Abdominal imaging (CT scan, sonogram, MRI): Imaging is not normally required and should only be considered in patients with symptoms suggesting biliary disease or to exclude biliary obstruction if the alkaline phosphatase is elevated more than the transaminases. Imaging may show hepatomegaly, but splenomegaly and ascites typically are absent.

Other Tests

  • Liver biopsy: Biopsy rarely is indicated for evaluation of acute hepatitis because the histologic features typically are nonspecific.

Histologic Findings

Liver histology closely resembles that of acute viral hepatitis and includes ballooning degeneration, sinusoidal acidophilic bodies, and focal necrosis occasionally accompanied by slight cholestasis. Necrosis is more extensive in cases that are more severe. Inflammatory infiltrates with lymphocytes and plasma cells are common, while eosinophilic infiltrates rarely are seen.

More on Isoniazid Hepatotoxicity

Overview: Isoniazid Hepatotoxicity
Differential Diagnoses & Workup: Isoniazid Hepatotoxicity
Treatment & Medication: Isoniazid Hepatotoxicity
Follow-up: Isoniazid Hepatotoxicity
Multimedia: Isoniazid Hepatotoxicity
References
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References

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Further Reading

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Keywords

isoniazid hepatitis, isonicotinic acid hydrazide, INH, antituberculosis therapy, jaundice, liver failure, drug toxicity

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Contributor Information and Disclosures

Author

Richard A Weisiger, MD, PhD, Director, GI and Liver Faculty Practice, Professor, Department of Internal Medicine, University of California San Francisco
Richard A Weisiger, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and American Society for Clinical Investigation Central
Disclosure: Nothing to disclose.

Medical Editor

Terence David Lewis, MBBS, FRACP, FRCPC, FACP, Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center
Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Douglas M Heuman, MD, FACP, Director of Hepatology, McGuire Veterans Affairs Medical Center, Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
Douglas M Heuman, MD, FACP is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
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 and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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