Isoniazid-rifampin-induced hepatitis in hepatitis B carriers

Wu, Jaw–Ching; Lee, Shou‐Dong; Yeh, Pen-Feng; Chan, Cho‐Yu; Wang, Yan-Jenn; Huang, Yo-Ping; Tsai, Yang‐Te; Lee, Pui Yuen; Ting, Ling-Pai; Lo, Kwang‐Juei

doi:10.1016/0016-5085(90)90846-s

Cited by 91 publications

(63 citation statements)

References 7 publications

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“…One report from Taiwan suggested that there is a higher incidence of ATT-induced fulminant and subacute hepatic failure in hepatitis B virus carriers compared to noncarriers [18], though some other studies have failed to notice any difference [19]. Another study has reported that the presence of chronic liver disease does not confer any additional risk of ATT-induced hepatitis.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Anand

Seth

Paul³

et al. 2006

Medical Journal Armed Forces India

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Background: Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. Methods: Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher's exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. Results: Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATTinduced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. Conclusion: ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases. MJAFI 2006; 62 : 45-49

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Section: Discussionmentioning

confidence: 99%

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Anand

Seth

Paul³

et al. 2006

Medical Journal Armed Forces India

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“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] The incidence of antituberculosis drug-induced hepatitis ranges from 1% to 36%, depending on different regimens and definitions of hepatic injury. [3][4][5][6][7][8][9][10][11][12][13][14][15] This hepatotoxicity is also the most prevalent drug-induced hepatic injury in Taiwan and many other countries, and its associated mortality is not rare. 10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis.…”

mentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11][12][13][14][15] This hepatotoxicity is also the most prevalent drug-induced hepatic injury in Taiwan and many other countries, and its associated mortality is not rare. 10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis. [3][4][5][6][7][8][9][10][11][12][13][14][15] However, the exact mechanism for this hepatotoxicity remains unclear.…”

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confidence: 99%

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Cytochrome P450 2E1 Genotype and the Susceptibility to Antituberculosis Drug–Induced Hepatitis

Yi¹,

et al. 2003

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Most cases with antituberculosis drug-induced hepatitis have been attributed to isoniazid. Isoniazid is metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. However, the role of CYP2E1 in this hepatotoxicity has not yet been reported. The aim of this study was to evaluate whether the polymorphism of the CYP2E1 gene is associated with antituberculosis drug-induced hepatitis. A total of 318 tuberculosis patients who received antituberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using a polymerase chain reaction with restriction fragment length polymorphism method. Twenty-one healthy volunteers were recruited for CYP2E1 phenotype study using a chlorzoxazone test. Forty-nine (15.4%) patients were diagnosed to have drug-induced hepatotoxicity. Patients with homozygous wild genotype CYP2E1 c1/c1 had a higher risk of hepatotoxicity (20.0%; odds ratio [OR], 2.52) than those with mutant allele c2 (CYP2E1 c1/c2 or c2/c2, 9.0%, P ‫؍‬ .009). If CYP2E1 c1/c2 or c2/c2 genotype combined with rapid acetylator status was regarded as the reference group, the risk of hepatotoxicity increased from 3.94 for CYP2E1 c1/c1 with rapid acetylator status to 7.43 for CYP2E1 c1/c1 with slow acetylator status. After adjustment for acetylator status and age, the CYP2E1 c1/c1 genotype remained an independent risk factor for hepatotoxicity (OR, 2.38; P ‫؍‬ .017). Furthermore, under the administration of isoniazid, the volunteers with CYP2E1 c1/c1 genotype had higher CYP2E1 activity than those with other genotypes had and, hence, might produce more hepatotoxins. In conclusion, CYP 2E1 genetic polymorphism may be associated with susceptibility to antituberculosis drug-induced hepatitis. (HEPATOLOGY 2003;37:924-930.)

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“…While hepatotoxicity due to RMP and INH is well documented [110, 114, 115], there are not many studies detailing the mechanisms behind liver injury induced by these drugs. Many risk factors such as age, alcohol consumption, gender and underlying diseases such as hepatitis B and C or cirrhosis could make TB patients undergoing anti-TB treatment more susceptible to RMP and INH hepatotoxicity [116–118]. …”

Section: Rifampin and Isoniazid Hepatotoxicitymentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Isoniazid-rifampin-induced hepatitis in hepatitis B carriers

Cited by 91 publications

References 7 publications

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Cytochrome P450 2E1 Genotype and the Susceptibility to Antituberculosis Drug–Induced Hepatitis

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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