Skip to main content
NCBI home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1993 Nov;159(5):560–564.

Fatal isoniazid-induced hepatitis. Its risk during chemoprophylaxis.

S R Salpeter 1
PMCID: PMC1022345  PMID: 8279152

Abstract

Isoniazid chemoprophylaxis has long been known to be a highly effective means of preventing silent tuberculous infections from spreading to active disease. There has been much controversy, however, about the risk it carries for fatal hepatotoxicity. In this article I review the rate of fatal isoniazid-induced hepatitis during chemoprophylaxis that is done according to current monitoring guidelines. Information was obtained from a MEDLINE literature search and a survey of tuberculosis control officers in large metropolitan areas throughout the country. Data were included of patients who were monitored according to the American Thoracic Society's guidelines or who were treated after 1983 when the guidelines were published. The pooled results of the published studies showed no hepatotoxic deaths in 20,212 patients in whom prophylaxis was started. The unpublished data showed 2 deaths in 182,285 patients, for a combined rate of 0.001% (2 of 202,497). The death rate for those older than 35 years was estimated to be 0.002% (1 of 43,334). This rate is significantly lower than was previously estimated and should be used to reevaluate the benefit of preventive therapy for tuberculin-reactive patients older than 35. The risk of fatal isoniazid-induced hepatitis is negligible for all ages when patients are routinely monitored for liver toxicity.

Full text

PDF
560

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcabes P., Vossenas P., Cohen R., Braslow C., Michaels D., Zoloth S. Compliance with isoniazid prophylaxis in jail. Am Rev Respir Dis. 1989 Nov;140(5):1194–1197. doi: 10.1164/ajrccm/140.5.1194. [DOI] [PubMed] [Google Scholar]
  2. Bailey W. C., Taylor S. L., Dascomb H. E., Greenberg H. B., Ziskind M. M. Disturbed hepatic function during isoniazid chemoprophylaxis. Monitoring the hepatic function of 427 hospital employees receiving isoniazid chemoprophylaxis for tuberculosis. Am Rev Respir Dis. 1973 Apr;107(4):523–529. doi: 10.1164/arrd.1973.107.4.523. [DOI] [PubMed] [Google Scholar]
  3. Bailey W. C., Weill H., DeRouen T. A., Ziskind M. M., Jackson H. A. The effect of isoniazid on transaminase levels. Ann Intern Med. 1974 Aug;81(2):200–202. doi: 10.7326/0003-4819-81-2-200. [DOI] [PubMed] [Google Scholar]
  4. Beaudry P. H., Brickman H. F., Wise M. B., MacDougall D. Liver enzyme disturbances during isoniazid chemoprophylaxis in children. Am Rev Respir Dis. 1974 Nov;110(5):581–584. doi: 10.1164/arrd.1974.110.5.581. [DOI] [PubMed] [Google Scholar]
  5. Byrd C. B., Nelson R., Elliott R. C. Isoniazid toxicity. A prospective study in secondary chemoprophylaxis. JAMA. 1972 Jun 12;220(11):1471–1473. doi: 10.1001/jama.220.11.1471. [DOI] [PubMed] [Google Scholar]
  6. Byrd R. B., Horn B. R., Solomon D. A., Griggs G. A. Toxic effects of isoniazid in tuberculosis chemoprophylaxis. Role of biochemical monitoring in 1,000 patients. JAMA. 1979 Mar 23;241(12):1239–1241. [PubMed] [Google Scholar]
  7. Colice G. L. Decision analysis, public health policy, and isoniazid chemoprophylaxis for young adult tuberculin skin reactors. Arch Intern Med. 1990 Dec;150(12):2517–2522. [PubMed] [Google Scholar]
  8. Cooper J. K. Decision analysis for tuberculosis preventive treatment in nursing homes. J Am Geriatr Soc. 1986 Nov;34(11):814–817. doi: 10.1111/j.1532-5415.1986.tb03988.x. [DOI] [PubMed] [Google Scholar]
  9. Dash L. A., Comstock G. W., Flynn J. P. Isoniazid preventive therapy: Retrospect and prospect. Am Rev Respir Dis. 1980 Jun;121(6):1039–1044. doi: 10.1164/arrd.1980.121.6.1039. [DOI] [PubMed] [Google Scholar]
  10. Dickinson D. S., Bailey W. C., Hirschowitz B. I., Soong S. J., Eidus L., Hodgkin M. M. Risk factors for isoniazid (NIH)-induced liver dysfunction. J Clin Gastroenterol. 1981 Sep;3(3):271–279. doi: 10.1097/00004836-198109000-00012. [DOI] [PubMed] [Google Scholar]
  11. Dutt A. K., Moers D., Stead W. W. Smear- and culture-negative pulmonary tuberculosis: four-month short-course chemotherapy. Am Rev Respir Dis. 1989 Apr;139(4):867–870. doi: 10.1164/ajrccm/139.4.867. [DOI] [PubMed] [Google Scholar]
  12. Dutt A. K., Moers D., Stead W. W. Smear-negative, culture-positive pulmonary tuberculosis. Six-month chemotherapy with isoniazid and rifampin. Am Rev Respir Dis. 1990 May;141(5 Pt 1):1232–1235. doi: 10.1164/ajrccm/141.5_Pt_1.1232. [DOI] [PubMed] [Google Scholar]
  13. Felten M. K., van der Merwe C. A. Random variation in tuberculin sensitivity in schoolchildren. Serial skin testing before and after preventive treatment for tuberculosis. Am Rev Respir Dis. 1989 Oct;140(4):1001–1006. doi: 10.1164/ajrccm/140.4.1001. [DOI] [PubMed] [Google Scholar]
  14. Ferebee S. H. Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl Tuberc. 1970;26:28–106. [PubMed] [Google Scholar]
  15. Fitzgerald J. M., Gafni A. A cost-effectiveness analysis of the routine use of isoniazid prophylaxis in patients with a positive Mantoux skin test. Am Rev Respir Dis. 1990 Oct;142(4):848–853. doi: 10.1164/ajrccm/142.4.848. [DOI] [PubMed] [Google Scholar]
  16. Franks A. L., Binkin N. J., Snider D. E., Jr, Rokaw W. M., Becker S. Isoniazid hepatitis among pregnant and postpartum Hispanic patients. Public Health Rep. 1989 Mar-Apr;104(2):151–155. [PMC free article] [PubMed] [Google Scholar]
  17. Garibaldi R. A., Drusin R. E., Ferebee S. H., Gregg M. B. Isoniazid-associated hepatitis. Report of an outbreak. Am Rev Respir Dis. 1972 Sep;106(3):357–365. doi: 10.1164/arrd.1972.106.3.357. [DOI] [PubMed] [Google Scholar]
  18. Glassroth J., Bailey W. C., Hopewell P. C., Schecter G., Harden J. W. Why tuberculosis is not prevented. Am Rev Respir Dis. 1990 May;141(5 Pt 1):1236–1240. doi: 10.1164/ajrccm/141.5_Pt_1.1236. [DOI] [PubMed] [Google Scholar]
  19. Grzybowski S., Ashley M. J., Pinkus G. Chemoprophylaxis in inactive tuberculosis: long-term evaluation of a Canadian trial. Can Med Assoc J. 1976 Apr 3;114(7):607–611. [PMC free article] [PubMed] [Google Scholar]
  20. Gurumurthy P., Krishnamurthy M. S., Nazareth O., Parthasarathy R., Sarma G. R., Somasundaram P. R., Tripathy S. P., Ellard G. A. Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis. Am Rev Respir Dis. 1984 Jan;129(1):58–61. doi: 10.1164/arrd.1984.129.1.58. [DOI] [PubMed] [Google Scholar]
  21. Hsu K. H. Isoniazid in the prevention and treatment of tuberculosis. A 20-year study of the effectiveness in children. JAMA. 1974 Jul 29;229(5):528–533. [PubMed] [Google Scholar]
  22. Jordan T. J., Lewit E. M., Reichman L. B. Isoniazid preventive therapy for tuberculosis. Decision analysis considering ethnicity and gender. Am Rev Respir Dis. 1991 Dec;144(6):1357–1360. doi: 10.1164/ajrccm/144.6.1357. [DOI] [PubMed] [Google Scholar]
  23. Kopanoff D. E., Snider D. E., Jr, Caras G. J. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis. 1978 Jun;117(6):991–1001. doi: 10.1164/arrd.1978.117.6.991. [DOI] [PubMed] [Google Scholar]
  24. Levin M. L., Moodie A. S. Isoniazid prophylaxis and deaths in Baltimore, 1972. Md State Med J. 1974 Nov;23(11):64–67. [PubMed] [Google Scholar]
  25. Litt I. F., Cohen M. I., McNamara H. Isoniazid hepatitis in adolescents. J Pediatr. 1976 Jul;89(1):133–135. doi: 10.1016/s0022-3476(76)80949-3. [DOI] [PubMed] [Google Scholar]
  26. Mehta J. B., Dutt A. K., Harvill L., Henry W. Isoniazid preventive therapy for tuberculosis. Are we losing our enthusiasm? Chest. 1988 Jul;94(1):138–141. doi: 10.1378/chest.94.1.138. [DOI] [PubMed] [Google Scholar]
  27. Mitchell J. R., Long M. W., Thorgeirsson U. P., Jollow D. J. Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy. Chest. 1975 Aug;68(2):181–190. doi: 10.1378/chest.68.2.181. [DOI] [PubMed] [Google Scholar]
  28. Mori M. A., Leonardson G., Welty T. K. The benefits of isoniazid chemoprophylaxis and risk factors for tuberculosis among Oglala Sioux Indians. Arch Intern Med. 1992 Mar;152(3):547–550. [PubMed] [Google Scholar]
  29. Moulding T. S., Redeker A. G., Kanel G. C. Twenty isoniazid-associated deaths in one state. Am Rev Respir Dis. 1989 Sep;140(3):700–705. doi: 10.1164/ajrccm/140.3.700. [DOI] [PubMed] [Google Scholar]
  30. Nakajo M. M., Rao M., Steiner P. Incidence of hepatotoxicity in children receiving isoniazid chemoprophylaxis. Pediatr Infect Dis J. 1989 Sep;8(9):649–650. doi: 10.1097/00006454-198909000-00019. [DOI] [PubMed] [Google Scholar]
  31. Nolan C. M., Aitken M. L., Elarth A. M., Anderson K. M., Miller W. T. Active tuberculosis after isoniazid chemoprophylaxis of Southeast Asian refugees. Am Rev Respir Dis. 1986 Mar;133(3):431–436. doi: 10.1164/arrd.1986.133.3.431. [DOI] [PubMed] [Google Scholar]
  32. Quillan S., Malotte C. K., Shlian D. Evaluation of a tuberculosis screening and prophylaxis program for international students. J Am Coll Health. 1990 Jan;38(4):165–170. doi: 10.1080/07448481.1990.9938437. [DOI] [PubMed] [Google Scholar]
  33. Rabindran E., Matuszak D. L., Israel E., Woodall H., Highsmith H., Flynn J. Preventive therapy for tuberculosis in Maryland. Md Med J. 1991 Sep;40(9):793–797. [PubMed] [Google Scholar]
  34. Rapp R. S., Campbell R. W., Howell J. C., Kendig E. L., Jr Isoniazid hepatotoxicity in children. Am Rev Respir Dis. 1978 Oct;118(4):794–796. doi: 10.1164/arrd.1978.118.4.794. [DOI] [PubMed] [Google Scholar]
  35. Rose D. N., Schechter C. B., Fahs M. C., Silver A. L. Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis. Am J Prev Med. 1988 Mar-Apr;4(2):102–109. [PubMed] [Google Scholar]
  36. Rose D. N., Schechter C. B., Silver A. L. The age threshold for isoniazid chemoprophylaxis. A decision analysis for low-risk tuberculin reactors. JAMA. 1986 Nov 21;256(19):2709–2713. [PubMed] [Google Scholar]
  37. Salpeter S. Tuberculosis chemoprophylaxis. West J Med. 1992 Oct;157(4):421–424. [PMC free article] [PubMed] [Google Scholar]
  38. Scharer L., Smith J. P. Serum transaminase elevations and other hepatic abnormalities in patients receiving isoniazid. Ann Intern Med. 1969 Dec;71(6):1113–1120. doi: 10.7326/0003-4819-71-6-1113. [DOI] [PubMed] [Google Scholar]
  39. Snider D. E., Jr, Caras G. J. Isoniazid-associated hepatitis deaths: a review of available information. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):494–497. doi: 10.1164/ajrccm/145.2_Pt_1.494. [DOI] [PubMed] [Google Scholar]
  40. Spyridis P., Sinaniotis C., Papadea I., Oreopoulos L., Hadjiyiannis S., Papadatos C. Isoniazid liver injury during chemoprophylaxis in children. Arch Dis Child. 1979 Jan;54(1):65–67. doi: 10.1136/adc.54.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stead W. W., To T., Harrison R. W., Abraham J. H., 3rd Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann Intern Med. 1987 Dec;107(6):843–845. doi: 10.7326/0003-4819-107-6-843. [DOI] [PubMed] [Google Scholar]
  42. Taylor W. C., Aronson M. D., Delbanco T. L. Should young adults with a positive tuberculin test take isoniazid? Ann Intern Med. 1981 Jun;94(6):808–813. doi: 10.7326/0003-4819-94-6-808. [DOI] [PubMed] [Google Scholar]
  43. Thomas P. A., Jr, Mozes M. F., Jonasson O. Hepatic dysfunction during isoniazid chemoprophylaxis in renal allograft recipients. Arch Surg. 1979 May;114(5):597–599. doi: 10.1001/archsurg.1979.01370290047008. [DOI] [PubMed] [Google Scholar]
  44. Thompson J. E. How safe is isoniazid? Med J Aust. 1978 Feb 11;1(3):165–169. doi: 10.5694/j.1326-5377.1978.tb107815.x. [DOI] [PubMed] [Google Scholar]
  45. Tsevat J., Taylor W. C., Wong J. B., Pauker S. G. Isoniazid for the tuberculin reactor: take it or leave it. Am Rev Respir Dis. 1988 Jan;137(1):215–220. doi: 10.1164/ajrccm/137.1.215. [DOI] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES