0
May 1973, Vol 125, No. 5 >
Article | May 1973

Isoniazid Administration and Liver Injury FREE

Raul Rudoy, MD; John Stuemky, MD; J. Rainer Poley, MD
[+] Author Affiliations

Received for publication Aug 21, 1972; accepted Dec 29.

Reprint requests to Children's Memorial Hospital, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City 73190 (Dr. Poley).


Am J Dis Child. 1973;125(5):733-736. doi:10.1001/archpedi.1973.04160050077016.
Text Size: A A A
Published online
Article
References
Comments

Isoniazid has been recognized as a cause of liver dysfunction in some patients receiving antituberculous therapy. The medical literature contains reports of isoniazid-induced hepatic injury in adults, but essentially none in children. We used this drug to treat a 6-year-old Caucasian boy for active tuberculosis, and he suffered a reaction characterized by high fever, a morbilliform exanthem, peripheral eosinophilia, enlargement of the liver, and abnormal liver function and histologic findings. The histologic appearance of the liver lesion and the clinical manifestations were suggestive of a hypersensitivity reaction, probably of the delayed type.

REFERENCES

1 +
Evans DA, Manley KA, McKusick VA:  Genetic control of isoniazid metabolism in man . Br Med J 2:485-491, 1960;.
2 +
American Thoracic Society:  Chemoprophylaxis for the prevention of tuberculosis: Statement by an ad hoc committee . Am Rev Resp Dis 96:558-560, 1967;.
3 +
Curry FJ:  Prophylactic effect of isoniazid in young tuberculin reactors . N Engl J Med 277:562-567, 1967;.
4 +
Biehl JP, Nimitz HJ:  Studies on the use of a high dose of isoniazid: I. Toxicity studies . Am Rev Tuberc 70:430-441, 1954;.
5 +
Randolph H, Joseph S:  Toxic hepatitis with jaundice occurring in a patient treated with isoniazid . JAMA 152:38-40, 1953;.
6 +
Merritt AD, Fetter BF:  Toxic hepatic necrosis (hepatitis) due to isoniazid: Report of a case with cirrhosis and death due to hemorrhage from esophageal varices . Ann Intern Med 50:804-810, 1959;.
7 +
Haber E, Osborne RK:  Icterus and febrile reactions to isonicotinic acid hydrazine: Report of 2 cases and review of the literature . N Engl J Med 260:417-420, 1959;.
8 +
Berte SJ, DiMase JD, Christianson C:  Isoniazid, para-aminosalicylic acid, and streptomycin intolerance in 1,744 patients: An analysis of reactions to single drugs and drug groups plus data on multiple reactions, and desensitization . Am Rev Resp Dis 90:598-606, 1964;.
9 +
Lal S, et al:  Effect of rifampicin and isoniazid on liver function . Br Med J 1:148-150, 1972;.
10 +
Garibaldi RA, et al:  Isoniazid-associated hepatitis: Report of an outbreak . Am Rev Resp Dis 106:357-365, 1972;.
11 +
Isoniazid and liver disease:  Report of the ad hoc committee on isoniazid and liver disease, Center for Disease Control, Department of Health, Education and Welfare, March 17-18, 1971 . Am Rev Resp Dis 104:454-459, 1971;.
12 +
Cohen R, Kaiser MH, Thomson RV:  Fatal hepatic necrosis secondary to isoniazid therapy . JAMA 176:877-879, 1961;.
13 +
Reynolds E:  Isoniazid jaundice and its relationship to iproniazid jaundice . Tubercle 43:375-381, 1962;.
14 +
Ristich C, Kourtèche K:  Sur un cas d'intoxication aigue par isonicotinylhydrazine . Rev Tuberc 18:817-819, 1954;.
15 +
Davies D, Glowinski JJ:  Jaundice due to isoniazid . Tubercle 42:504-506, 1961;.
16 +
Popper H, et al:  Mechanisms of intrahepatic cholestasis in drug-induced hepatic injury . Ann NY Acad Sci 104:988-1013, 1963;.
17 +
Popper H, et al:  Drug-induced liver disease: A penalty for progress . Arch Intern Med 115:128-136, 1965;.
18 +
Scharer L, Smith JP:  Serum transaminase elevations and other hepatic abnormalities in patients receiving isoniazid . Ann Intern Med 71:1113-1120, 1969;.
19 +
Martin CE, Arthaud JB:  Hepatitis after isoniazid administration . N Engl J Med 282:433-434, 1970;.
20 +
Lichtenstein MR, Cannemeyer W:  Severe p-aminosalicylic acid hypersensitivity simulating mononucleosis or hepatitis . JAMA 152:606-607, 1952;.
21 +
Bellamy WE Jr, et al:  Jaundice associated with the administration of sodium p-aminosalicylic acid: Review of the literature and report of a case . Ann Intern Med 44:764-772, 1956;.
22 +
Paine D:  Fatal hepatic necrosis associated with amino-salicylic acid: Review of the literature and report of a case . JAMA 167:285-289, 1958;.
23 +
Simpson DG, Walker HJ:  Hypersensitivity to para-aminosalicyclic acid . Am J Med 29:297-306, 1960;.
24 +
Fount FW, Ferebee SH:  Preventive effects of isoniazid in the treatment of primary tuberculosis in children . N Engl J Med 265:713-721, 1961;.
25 +
Blattner RJ:  Isoniazid prophylaxis in tuberculin reactors . J Pediatr 72:131-133, 1968;.
26 +
Carr EA Jr:  Drug allergy . Pharmacol Rev 6:365-424, 1954;.
27 +
Göcken M, Zinneman HH:  Liver "autoantibodies" in a case of drug-induced jaundice . Gastroenterology 44:69-72, 1959;.
28 +
Bloodworth JM Jr, Hamwi GJ:  Histopathologic lesions associated with sulfonylurea administration . Diabetes 10:90-99, 1961;.
29 +
Goldstein G:  Sarcoid reaction associated with phenylbutazone hypersensitivity . Ann Intern Med 59:97-100, 1963;.
30 +
Steiner JW:  Investigation of allergic liver injury: I. Light, fluorescent and electron microscopic study of effects of soluble immune aggregates . Am J Pathol 38:411-436, 1961;.
31 +
Litt M:  Studies in experimental eosinophilia: IV. Determinants of eosinophil localization . J Allergy 33:532-543, 1962;.
32 +
Rubin B, et al:  Pharmacology of isonicotinic acid hydrazide (Nydrazid) . Am Rev Tuberc 65:392-401, 1952;.
33 +
Smith J, et al:  Hepatotoxicity in rifampin-isoniazid treated patients related to their rate of isoniazid inactivation . Chest 61:587-588, 1972;.
34 +
Hughes HB:  On the metabolic fate of isoniazid . J Pharmacol Exp Therap 109:444-452, 1953;.
35 +
Jeanes CWL, Schaefer 0, Eidus L:  Inactivation of isoniazid by Canadian Eskimos and Indians . Can Med Assoc J 106:331-335, 1972;.
36 +
Evans DAP:  An improved and simplified method of detecting the acetylator phenotype . J Med Genet 6:405-407, 1969;.
37 +
Hanngren A, Borga O, Sjoeqvist F:  Inactivation of isoniazid (INH) in Swedish tuberculous patients before and during treatment with para-aminosalicylic acid (PAS) . Scand J Resp Dis 51:61-69, 1970;.
38 +
Harris HW, Knight RA, Selin MJ:  Comparison of isoniazid concentrations in the blood of people of Japanese and European descent: Therapeutic and genetic implications . Am Rev Tuberc 78:944-948, 1958;.
39 +
Lesobre R, et al:  Les ictères au cours du traitement par la rifampicine . Rev Tuberc Pnéumonol 33:393-403, 1969;.
40 +
Lees AW, et al:  Jaundice after rifampicin . Br J Dis Chest 64:90-95, 1970;.
41 +
Chevrel B:  Rifampicine et foie . Presse Méd 79:1911-1912, 1971;.
42 +
Riska N, Mattson K:  Adverse reactions during rifampicin treatment . Scand J Resp Dis 53:87-96, 1972;.
43 +
Bobrowitz, cited by Lederman RJ, Davis FB, Davis PJ:  Exchange transfusion as treatment of acute hepatic failure due to antituberculous drugs . Ann Intern Med 68:830-838, 1968;.
44 +
Assem ES, et al:  Liver damage and isoniazid allergy . Clin Exp Immunol 5:439-442, 1969;.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Evans DA, Manley KA, McKusick VA:  Genetic control of isoniazid metabolism in man . Br Med J 2:485-491, 1960;.
2 +
American Thoracic Society:  Chemoprophylaxis for the prevention of tuberculosis: Statement by an ad hoc committee . Am Rev Resp Dis 96:558-560, 1967;.
3 +
Curry FJ:  Prophylactic effect of isoniazid in young tuberculin reactors . N Engl J Med 277:562-567, 1967;.
4 +
Biehl JP, Nimitz HJ:  Studies on the use of a high dose of isoniazid: I. Toxicity studies . Am Rev Tuberc 70:430-441, 1954;.
5 +
Randolph H, Joseph S:  Toxic hepatitis with jaundice occurring in a patient treated with isoniazid . JAMA 152:38-40, 1953;.
6 +
Merritt AD, Fetter BF:  Toxic hepatic necrosis (hepatitis) due to isoniazid: Report of a case with cirrhosis and death due to hemorrhage from esophageal varices . Ann Intern Med 50:804-810, 1959;.
7 +
Haber E, Osborne RK:  Icterus and febrile reactions to isonicotinic acid hydrazine: Report of 2 cases and review of the literature . N Engl J Med 260:417-420, 1959;.
8 +
Berte SJ, DiMase JD, Christianson C:  Isoniazid, para-aminosalicylic acid, and streptomycin intolerance in 1,744 patients: An analysis of reactions to single drugs and drug groups plus data on multiple reactions, and desensitization . Am Rev Resp Dis 90:598-606, 1964;.
9 +
Lal S, et al:  Effect of rifampicin and isoniazid on liver function . Br Med J 1:148-150, 1972;.
10 +
Garibaldi RA, et al:  Isoniazid-associated hepatitis: Report of an outbreak . Am Rev Resp Dis 106:357-365, 1972;.
11 +
Isoniazid and liver disease:  Report of the ad hoc committee on isoniazid and liver disease, Center for Disease Control, Department of Health, Education and Welfare, March 17-18, 1971 . Am Rev Resp Dis 104:454-459, 1971;.
12 +
Cohen R, Kaiser MH, Thomson RV:  Fatal hepatic necrosis secondary to isoniazid therapy . JAMA 176:877-879, 1961;.
13 +
Reynolds E:  Isoniazid jaundice and its relationship to iproniazid jaundice . Tubercle 43:375-381, 1962;.
14 +
Ristich C, Kourtèche K:  Sur un cas d'intoxication aigue par isonicotinylhydrazine . Rev Tuberc 18:817-819, 1954;.
15 +
Davies D, Glowinski JJ:  Jaundice due to isoniazid . Tubercle 42:504-506, 1961;.
16 +
Popper H, et al:  Mechanisms of intrahepatic cholestasis in drug-induced hepatic injury . Ann NY Acad Sci 104:988-1013, 1963;.
17 +
Popper H, et al:  Drug-induced liver disease: A penalty for progress . Arch Intern Med 115:128-136, 1965;.
18 +
Scharer L, Smith JP:  Serum transaminase elevations and other hepatic abnormalities in patients receiving isoniazid . Ann Intern Med 71:1113-1120, 1969;.
19 +
Martin CE, Arthaud JB:  Hepatitis after isoniazid administration . N Engl J Med 282:433-434, 1970;.
20 +
Lichtenstein MR, Cannemeyer W:  Severe p-aminosalicylic acid hypersensitivity simulating mononucleosis or hepatitis . JAMA 152:606-607, 1952;.
21 +
Bellamy WE Jr, et al:  Jaundice associated with the administration of sodium p-aminosalicylic acid: Review of the literature and report of a case . Ann Intern Med 44:764-772, 1956;.
22 +
Paine D:  Fatal hepatic necrosis associated with amino-salicylic acid: Review of the literature and report of a case . JAMA 167:285-289, 1958;.
23 +
Simpson DG, Walker HJ:  Hypersensitivity to para-aminosalicyclic acid . Am J Med 29:297-306, 1960;.
24 +
Fount FW, Ferebee SH:  Preventive effects of isoniazid in the treatment of primary tuberculosis in children . N Engl J Med 265:713-721, 1961;.
25 +
Blattner RJ:  Isoniazid prophylaxis in tuberculin reactors . J Pediatr 72:131-133, 1968;.
26 +
Carr EA Jr:  Drug allergy . Pharmacol Rev 6:365-424, 1954;.
27 +
Göcken M, Zinneman HH:  Liver "autoantibodies" in a case of drug-induced jaundice . Gastroenterology 44:69-72, 1959;.
28 +
Bloodworth JM Jr, Hamwi GJ:  Histopathologic lesions associated with sulfonylurea administration . Diabetes 10:90-99, 1961;.
29 +
Goldstein G:  Sarcoid reaction associated with phenylbutazone hypersensitivity . Ann Intern Med 59:97-100, 1963;.
30 +
Steiner JW:  Investigation of allergic liver injury: I. Light, fluorescent and electron microscopic study of effects of soluble immune aggregates . Am J Pathol 38:411-436, 1961;.
31 +
Litt M:  Studies in experimental eosinophilia: IV. Determinants of eosinophil localization . J Allergy 33:532-543, 1962;.
32 +
Rubin B, et al:  Pharmacology of isonicotinic acid hydrazide (Nydrazid) . Am Rev Tuberc 65:392-401, 1952;.
33 +
Smith J, et al:  Hepatotoxicity in rifampin-isoniazid treated patients related to their rate of isoniazid inactivation . Chest 61:587-588, 1972;.
34 +
Hughes HB:  On the metabolic fate of isoniazid . J Pharmacol Exp Therap 109:444-452, 1953;.
35 +
Jeanes CWL, Schaefer 0, Eidus L:  Inactivation of isoniazid by Canadian Eskimos and Indians . Can Med Assoc J 106:331-335, 1972;.
36 +
Evans DAP:  An improved and simplified method of detecting the acetylator phenotype . J Med Genet 6:405-407, 1969;.
37 +
Hanngren A, Borga O, Sjoeqvist F:  Inactivation of isoniazid (INH) in Swedish tuberculous patients before and during treatment with para-aminosalicylic acid (PAS) . Scand J Resp Dis 51:61-69, 1970;.
38 +
Harris HW, Knight RA, Selin MJ:  Comparison of isoniazid concentrations in the blood of people of Japanese and European descent: Therapeutic and genetic implications . Am Rev Tuberc 78:944-948, 1958;.
39 +
Lesobre R, et al:  Les ictères au cours du traitement par la rifampicine . Rev Tuberc Pnéumonol 33:393-403, 1969;.
40 +
Lees AW, et al:  Jaundice after rifampicin . Br J Dis Chest 64:90-95, 1970;.
41 +
Chevrel B:  Rifampicine et foie . Presse Méd 79:1911-1912, 1971;.
42 +
Riska N, Mattson K:  Adverse reactions during rifampicin treatment . Scand J Resp Dis 53:87-96, 1972;.
43 +
Bobrowitz, cited by Lederman RJ, Davis FB, Davis PJ:  Exchange transfusion as treatment of acute hepatic failure due to antituberculous drugs . Ann Intern Med 68:830-838, 1968;.
44 +
Assem ES, et al:  Liver damage and isoniazid allergy . Clin Exp Immunol 5:439-442, 1969;.

Correspondence

Submit a Letter
CME
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Clear Answers | Save For Later
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2013 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems