eMedicine Specialties > Gastroenterology > Liver

Isoniazid Hepatotoxicity: Follow-up

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

Follow-up

Further Inpatient Care

  • Monitor all patients until transaminases normalize.
  • Patients with minor elevations of the transaminases who continue to take isoniazid require frequent monitoring (as much as twice weekly).
  • Patients who have stopped using isoniazid because of transaminase elevations greater than 3 times the normal level should generally avoid subsequent use of isoniazid.
  • Reintroduction of isoniazid does not always produce hepatitis, suggesting environmental factors (eg, other medications, illness, malnutrition), which also may be important.

Transfer

  • Transfer patients with elevated prothrombin times to a hospital that offers access to liver transplantation. Early transfer carries less risk and permits more time to evaluate the patient for transplantation.

Deterrence/Prevention

The incidence of severe hepatitis and death may be reduced by the following:

  • Avoid prophylactic use of INH in older persons (eg, >35 y), unless the potential benefit clearly outweighs the risk. Treatment of tuberculin reactors is more strongly indicated in immunosuppressed persons and in those with a recent exposure history.
  • Obtain a baseline ALT prior to starting isoniazid when there is suspicion of prior liver disease.
  • Educate the patient to immediately report possible adverse effects of isoniazid hepatotoxicity. Interview the patient on a regular basis (eg, monthly) for adverse effects or monitor transaminases on a monthly basis.
  • Stop isoniazid immediately for any transaminase elevation greater than 3-fold above normal. Lesser elevations should prompt more frequent monitoring.
  • Where possible, avoid simultaneous administration of drugs that induce the cytochrome P-450 system (eg, phenobarbital, rifampin).
  • Avoid simultaneous use of other potentially hepatotoxic drugs (eg, pyrazinamide, protease inhibitors for HIV), unless the benefit of using them exceeds the risk of developing hepatitis.
  • Avoid heavy consumption of ethanol while on isoniazid.
  • Advise patients to avoid taking more than 3 g/d of acetaminophen (paracetamol) because of the reduced threshold for liver damage.
  • Animal studies suggest that certain antioxidants may reduce the risk of isoniazid hepatitis. These include silymarin, vitamin E, N- acetylcysteine, and melatonin. While it is not known if these results apply to humans, correcting nutritional deficiencies prior to starting isoniazid may be warranted.

Prognosis

  • Survival rates depend on the severity of the hepatitis.
  • Case fatality rates from 10-20% have been reported for those with overt isoniazid hepatitis.
  • Those who survive usually recover completely without residual liver damage.

Patient Education

  • Warn all patients started on isoniazid to immediately report any symptoms suggestive of hepatitis, including nausea, fatigue, jaundice, and abdominal distress.
  • Advise patients to avoid heavy use of alcohol or acetaminophen and to maintain good nutrition.

Miscellaneous

Medicolegal Pitfalls

  • Failure to obtain informed consent for the use of isoniazid
  • Failure to advise patients to immediately report any symptoms suggesting hepatitis
  • Failure to diagnose isoniazid hepatitis when symptoms are present
  • Failure to stop isoniazid (and any other potentially hepatotoxic drug) promptly when symptoms are first reported or when transaminases are elevated more than 3 times greater than the normal level.
  • Prophylactic use of isoniazid in older persons unless the benefits clearly outweigh the risks
 


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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