Chest
ReviewsToxic Hepatitis with Isoniazid and Rifampin: A Meta-analysis
Section snippets
INH-RELATED HEPATITIS; BRIEF HISTORY AND CLINICAL FEATURES
During the first few years after introduction of INH, only sporadic cases suggesting possible hepatotoxicity were noted, and jaundice developing in patients on treatment was often attributed to concurrent viral hepatitis or the toxic effects of other drugs such as PAS.2, 3, 4, 5, 6, 7 Berté and associates8 in 1959 stated that no case of hepatotoxicity was observed in 513 patients receiving INH, and such was its reputation for safety that in 1963 the American Thoracic Society recommended all
HEPATOTOXICITY ASSOCIATED WITH INH PLUS RMP
Soon after the introduction of RMP, several reports suggested that hepatitis was more frequent and severe in patients receiving both INH and RMP16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 than in those receiving INH alone. Lesobre and associates16 described 12 cases of jaundice with four deaths among 50 patients receiving INH and RMP, although many of these had pre-existing liver disease. Lees et al17 observed four cases among 50 patients without known antecedent liver disease and stated that in
METHODS
A Medline search of the English language literature was performed. Articles published between 1966 and December, 1989 were searched using the MESH terms “tuberculosis/drug therapy,” “human” and either “isoniazid” or “rifampin.” In addition, “isoniazid” and “rifampin” were searched as text words. The search output included 1,496 potentially relevant citations. The selection was further restricted by choosing only those articles describing clinical trials or surveys of public health departments,
RESULTS
Studies with data on the incidence of toxic hepatitis in adults receiving anti-tuberculosis drugs were sorted according to drug regimen, as indicated in the Methods section. Table 1 lists data on the incidence of hepatitis in adults taking INH chemoprophylaxis, as well as in those taking multiple-drug INH regimens without RMP. Table 2 summarizes data in adults taking multiple-drug RMP regimens without INH, and Table 3 lists studies of adults taking INH plus RMP combination therapy. In Table 3,
DISCUSSION
The data presented above support the opinion that toxic hepatitis complicates TB chemotherapy with INH plus RMP more frequently than regimens including one but not both of these drugs. While this effect was especially striking in children, it was also noted in adults. Unfortunately, the adult data could not be further adjusted according to known risk factors for toxic hepatitis such as age,13,63 acetylator status,19,37,42,43,44 and alcohol use.13,15,42,63 Another potential methodologic problem
REFERENCES (68)
- et al.
Isoniazid and PAS toxicity in 513 cases
Dis Chest
(1959) - et al.
Jaundice after rifampicin
Br J Dis Chest
(1970) - et al.
Side effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study
Tubercle
(1980) - et al.
Short-course chemotherapy for tuberculosis with mainly twice weekly isoniazid and rifampin. Community physicians seven-year experience with mainly outpatients
Am J Med
(1984) - et al.
Hepatotoxicity in rifampin-isoniazid treated patients related to their rate of isoniazid inactivation
Chest
(1972) - et al.
Toxicity from rifampin plus isoniazid and rifampicin plus ethambutol therapy
Tubercle
(1971) - et al.
Isoniazid-rifampin fulminant hepatitis. A possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction
Gastroenterology
(1977) - et al.
Isoniazid hepatitis in adolescents
Pediatric Pharmacology and Therapeutics
(1976) - et al.
The treatment of tuberculous meningitis in children with a combination of isoniazid, rifampicin, and streptomycin: Preliminary report
Tubercle
(1979) - et al.
Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide
Tubercle
(1986)
Isoniazid-associated hepatitis in 114 patients
Gastroenterology
Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy
Chest
Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin
Am Rev Respir Dis
Toxic hepatitis with jaundice occurring in a patient treated with isoniazid
JAMA
Fatal hepatic necrosis secondary to isoniazid therapy
JAMA
Isoniazid-induced liver disease
Seminars in Liver Disease
Controlled chemoprophylaxis trials in tuberculosis. A general review
Bibl Tuberc
Long-term chemotherapy in the treatment of chronic pulmonary tuberculosis with cavitation
Tubercle
Isoniazid para-aminosalicylic acid, and streptomycin tolerance in 1744 patients: an analysis of reactions to single drugs and drug groups plus data on multiple reactions, type and time of reactions and desensitization
Am Rev Respir Dis
Chemoprophylaxis for the prevention of tuberculosis; a statement by an ad-hoc committee
Am Rev Respir Dis
Serum transaminase elevations and other hepatic abnormalities in patients receiving isoniazid
Ann Intern Med
Isoniazid-associated hepatitis: report of an outbreak
Am Rev Respir Dis
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: Isoniazid and Liver Disease
Am Rev Resp Dis
Isoniazid-related hepatitis. A US Public Health Service Cooperative Surveillance Study
Am Rev Respir Dis
Isoniazid prophylaxis and deaths in Baltimore
Maryland State Med J
The competing risks of tuberculosis and hepatitis for adult tuberculin reactors. Editorial
Am Rev Respir Dis
Jaundice occurring during treatment with rifampicin
Rev Tuberc
Effect of rifampicin and isoniazid on liver function
Br Med J
Predisposing factors in hepatitis induced by isoniazid-rifampin treatment of tuberculosis
Am Rev Respir Dis
Six-month isoniazid-rifampin therapy for pulmonary tuberculosis. Report of a United States Health Service Cooperative Trial
Am Rev Respir Dis
The hepatic toxicity of antituberculosis regimens containing isoniazid, rifampicin and pyrazinamide
Tubercle
Short-course chemotherapy in pulmonary tuberculosis
Lancet
Rifampin-isoniazid therapy of alcoholic and nonalcoholic tuberculosis patients in a US Public Health Service Cooperative Therapy Trial
Am Rev Respir Dis
Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin
Pediatr Infect Dis.
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2022, Journal of NeuroimmunologyCitation Excerpt :In the present study, DIH occurred in 16% patients after starting ATT, and wasthe most common adverse effect leading to interruption of therapy. The reported incidence of DIH in western literature is 4.3%–19% (Steele et al., 1991; Ormerod et al., 1996; Thompson et al., 1995). In India, DIH has due to genetic susceptibility, acetylation status and other risk factors (Mushiroda et al., 2016; Sistanizad et al., 2011; Hemanth Kumar et al., 2017; Singh et al., 1995).