Predisposition of antituberculosis drug induced hepatotoxicity by cytochrome P450 2E1 genotype and haplotype in pediatric patients

Roy, Bidyut; Ghosh, Suparna; Sutradhar, Debabrata; Sikdar, Nilabja; Mazumder, Sonal; Barman, Santanu

doi:10.1111/j.1440-1746.2006.04197.x

Cited by 49 publications

(39 citation statements)

References 3 publications

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“…4,21 Although our study was not designed to determine the incidence of DILI secondary to ATDs, a meta-analysis reported a higher incidence of clinical hepatitis (6.9%) in children receiving INH and RIF, compared to 2.7% in adults, suggesting that children are at a higher risk for developing DILI. 22 Two recent studies, one from India 23 and another from Turkey, 24 reported an incidence of 8% and 1.7%, respectively, the former with 3 hepatotoxic drugs (INH, RIF, and PZY). Although children have long been considered to be at low risk for DILI, the finding from this and other studies suggests that AT DILI is an important cause of morbidity and mortality in children.…”

Section: Discussionmentioning

confidence: 99%

Drug-Induced liver injury with hypersensitivity features has a better outcome: A single-center experience of 39 children and adolescents

Devarbhavi

Karanth

et al. 2011

Hepatology

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Drug-induced liver injury (DILI) is rare in children and adolescents, and, consequently, data are remarkably limited. We analyzed the causes, clinical and biochemical features, natural history, and outcomes of children with DILI. Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on standard criteria for DILI. Thirty-nine children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls. Median age was 16 years (range, 2.6-17). Combination antituberculous drugs were the most common cause (n 5 22), followed by the anticonvulsants, phenytoin (n 5 10) and carbamazepine (n 5 6). All of the 16 children (41%) who developed hypersensitivity features, such as skin rashes, fever, lymphadenopathy, and/or eosinophilia, including the 3 with Stevens-Johnson syndrome, survived. Those with hypersensitivity presented earlier (24.5 versus 35 days; P 5 0.24) had less severe disease (MELD, 16 versus 29; P 5 0.01) and had no mortality (0/16 versus 12/23; P < 0.001), compared to those without hypersensitivity. The 12 fatalities were largely the result of antituberculous DILI (n 5 11). The presence of encephalopathy and ascites were associated with mortality, along with hyperbilirubinemia, high international normalized ratio, and serum creatinine. According to the Roussel Uclaf Causality Assessment Method, 18 were highly probable, 14 probable, and 7 possible. Thirty-two children were hospitalized. Conclusion: DILI is not uncommon in children and accounts for 8.7% of all patients with DILI. Antituberculous drugs and anticonvulsants are the leading causes of DILI in India. Overall mortality is high (30.7%), largely accounted by antituberculous drugs. Children with DILI and hypersensitivity features present early, have less severe disease, and, consequently, a better prognosis, compared to those without, and are often associated with anticonvulsants or sulfonamides. (HEPATOLOGY 2011;54:1344-1350 T he last decade has seen an increasing number of reports on drug-induced liver injury (DILI) in adults across all regions of the world.

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Section: Discussionmentioning

confidence: 99%

Drug-Induced liver injury with hypersensitivity features has a better outcome: A single-center experience of 39 children and adolescents

Devarbhavi

Karanth

et al. 2011

Hepatology

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“…Recent studies have demonstrated that genetic polymorphisms in drug-metabolising enzymes, which influence their activation capacity and the generation of metabolites in the liver, might predispose an individual to hepatic adverse reactions (Ohno et al 2000, Kita et al 2001, Roy et al 2001, Hiratsuka et al 2002, Huang et al 2002, 2003, 2007, Roy et al 2006, Leiro et al 2008.…”

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confidence: 99%

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Teixeira

Morato

Cabello

et al. 2011

Mem. Inst. Oswaldo Cruz

116

104

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“…Associations between GSTM1 null genotype and INH DILI were also shown in a recent meta-analysis [60] but such associations may be ethnicity specific [60,63,72]. GSTT1 null genotype, on the other hand, was not associated with hepatotoxicity in different ethnic populations [60,62,175].…”

Section: Antituberculous Drugsmentioning

confidence: 78%

“…However, of all the antituberculous drugs, only isoniazid pharmacogenomics have been extensively studied [60–63,65 – 67,72,174–182]. …”

Section: Antituberculous Drugsmentioning

confidence: 99%

“…While some studies, including a meta-analysis, showed that *1A/*1A genotype was associated with increased risk of INH DILI, particularly in combination with NAT2 slow acetylator status [61,66,177], other studies have not replicated the same findings [176,178], or significant association was found only in east Asians [60]. Variant CYP2E1*6 allele and *1A–*6 –*1D haplotype were also shown to be associated with increased risk of INH DILI [63] but CYP2E1*1C polymorphisms were not [179]. …”

Section: Antituberculous Drugsmentioning

confidence: 99%

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Pharmacogenomics of Antimicrobial Agents

et al. 2014

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Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.

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Predisposition of antituberculosis drug induced hepatotoxicity by cytochrome P450 2E1 genotype and haplotype in pediatric patients

Cited by 49 publications

References 3 publications

Drug-Induced liver injury with hypersensitivity features has a better outcome: A single-center experience of 39 children and adolescents

Drug-Induced liver injury with hypersensitivity features has a better outcome: A single-center experience of 39 children and adolescents

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Pharmacogenomics of Antimicrobial Agents

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