***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Most cases with anti-tuberculosis drug-induced hepatotoxicity ( ATDH ) have been attributed to isoniazid . OBJECTIVE To evaluate whether the polymorphisms of the cytochrome P450 2EI ( CYP2E1 ) and N-acetyltransferase 2 ( NAT2 ) gene are associated with ATDH . DESIGN A total of 140 tuberculosis ( TB ) patients without liver diseases before treatment who received anti-tuberculosis treatment  were followed prospect ively . Their CYP2E1 and NAT2 genotypes were determined using the TaqMan polymerase chain reaction assay . RESULTS Forty-five ( 32.1 % ) patients were diagnosed with ATDH . No significant differences were reported in age and sex between patients with and without ATDH . Slow acetylators defined by NAT2 genotypes had a higher risk of hepatotoxicity than rapid acetylators ( 51.2 % vs. 25.2 % , P = 0.0026 ) . Odds ratio ( OR ) analysis showed that slow acetylator status ( OR 3.15 , 95%CI 1.47 - 6.48 ) was the only independent risk factor for ATDH . Pyrazinamide co-administration induced hepatitis was also associated with NAT2 acetylator status . CYP2E1 c1/c1 homozygotes are prone to developing more severe hepatotoxicity than other c1/c2 and c2/c2 genotypes . CONCLUSION The slow acetylator status of NAT2 is a significant susceptibility risk factor for ATDH . CYP2E1 is associated with the severity of ATDH Purpose To determine the frequency of N-acetyltransferase 2 ( NAT2 ) polymorphisms , the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions ( ADRs ) , anti-tuberculosis ( TB ) drug-induced hepatotoxicity , and the clinical risk factors for hepatotoxicity in a population from Brazil . Methods Two hundred and fifty-four Brazilian TB patients using isoniazid ( INH ) , rifampicin ( RMP ) , and pirazinamide ( PZA ) were tested in a  prospect i ve cohort study . NAT2 genotyping was performed by direct PCR sequencing . The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression . Results Of the 254 patients analyzed , 69 ( 27.2 % ) were slow acetylators and 185 ( 72.8 % ) were fast acetylators . Sixty-five ( 25.6 % ) patients were human immunodeficiency virus (HIV)-positive . Thirty-three ( 13 % ) and 14 ( 5.5 % ) patients developed gastrointestinal ADR and hepatotoxicity , respectively . Of the 14 hepatotoxicity patients , nine ( 64.3 % ) were slow acetylators and five ( 35.7 % ) were fast acetylators . Sex , age , presence of hepatitis C virus , alcohol abuse , and baseline aminotransferases were not found to be risk factors for hepatotoxicity . However , logistic regression analysis revealed that slow acetylator status and the presence of HIV ( p < 0.05 ) were independent risk factors for hepatotoxicity . Conclusions Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs SETTING Japanese in- patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin ( INH + RMP ) .  OBJECTIVE To eluci date the relationship between N-acetyltransferase 2 ( NAT2 ) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity . DESIGN Prospect i ve study . After NAT2 * genotyping , 77 patients were classified into three groups according to their NAT2 * genotypes : rapid-type ( a homozygote of NAT2 * 4 ) , intermediate-type ( a heterozygote of NAT2 * 4 and mutant alleles ) and slow-type ( a combination of mutant alleles ) . Their biochemical profiles of liver function test were investigated for 3 months to assess the development of serum aminotransferase elevation . RESULT Of the 77 patients , 18.2 % developed adverse hepatic reaction within the first month of INH + RMP treatment . A significant association was observed between hepatotoxicity and NAT2 * genotype : compared with rapid-type , the relative risk was 4.0 ( 95 % CI 1.94 - 6.06 ) for intermediate-type and 28.0 ( 95%CI 26.0 - 30.0 ) for slow-type . Especially in slow-type , the incidence of hepatotoxicity and serum aminotransferase elevation was significantly higher than in the other two types . CONCLUSION Slow NAT2 * genotype significantly affected the development of INH + RMP-induced hepatotoxicity . This suggests the possibility that NAT2 * genotyping prior to medication may be useful in evaluating patients with high risk for INH + RMP-induced  hepatotoxicity WHAT IS KNOWN AND OBJECTIVE The pathogenic mechanism of antituberculosis drug-induced hepatotoxicity ( ATDH ) is thought to involve drug-metabolizing enzymes including N-acetyl transferase2 ( NAT2 ) , cytochrome P4502E1 ( CYP2E1 ) and glutathione S-transferase ( GST ) M1 , T1 . The associations between genetic polymorphisms of those genes and ATDH have been reported but with inconsistent results . Moreover , most studies were hospital-based retrospective studies and not prospect i ve . We aim ed to investigate possible associations of CYP2E1 , GSTM1 and GSTT1 genetic polymorphisms with ATDH using a more robust case-control study nested in a population -based prospect i ve antituberculosis treatment cohort . METHODS A total of 4304 patients with smear-positive tuberculosis ( TB ) who received st and ard short-course chemotherapy were monitored for 6 - 9 months . Incidence density sampling method was adopted to select controls and 4 : 1 matched with each ATDH cases by age ( ± 5 years ) , sex , treatment history , disease severity and drug dosage . The CYP2E1 , GSTM1 and GSTT1 polymorphisms were genotyped using PCR-RFLP and multiplex PCR methods . Conditional logistic regression model was used to calculate odds ratio ( OR ) and 95 % confidence interval ( CI ) , as well as corresponding P-values . RESULTS AND DISCUSSION A total of 89 ATDH cases and 356 controls were included in this study . There was no statistically significant association between CYP2E1 RsaI c1/c1 genotype or DraI C/C genotype and ATDH ( OR = 0·99 , 95 % CI:0·62 - 1·59 ; OR = 1·13 , 95 % CI : 0·40 - 3·20 , respectively ) compared with CYP2E1 RsaI c1/c2 or c2/c2 genotypes or DraI D/D genotype , or between GSTM1/GSTT1 null genotypes and ATDH ( OR = 1·22 , 95 % CI : 0·76 - 1·96 ; OR = 0·96 , 95 % CI : 0·60 - 1·52 , respectively ) compared with non-null genotypes . WHAT IS NEW AND CONCLUSION This is the first study of the involvement of CYP2E1 , GSTM1 and GSTT1 genetic polymorphisms in ATDH using a nested case-control population -based prospect i ve cohort design . We could not confirm positive associations of genetic polymorphisms of CYP2E1 RsaI , CYP2E1 DraI , GSTM1 null and GSTT1 null with ATDH reported by various groups , in our Chinese TB population Antituberculosis drug-induced hepatitis attributed to isoniazid ( INH ) is one of the most prevalent drug-induced liver injuries . INH is metabolized by hepatic N-acetyltransferase ( NAT ) and cytochrome P450 2E1 ( CYP2E1 ) to form hepatotoxins . The aim of this study was to evaluate whether polymorphisms of the NAT2 and /or CYP2E1 genes were associated with antituberculosis drug-induced hepatotoxicity in Korean patients . A total of 132 patients with tuberculosis who received antituberculosis treatment  were followed prospect ively . Their NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction ( PCR ) with or without sequencing . Eighteen ( 13.6 % ) patients developed antituberculosis drug-induced hepatotoxicity . Regarding NAT2 , slow acetylators had a higher incidence of hepatotoxicity than rapid acetylators ( 36.8 % vs. 9.7 % , P=0.005 ) and there was a 3.8-fold risk of hepatotoxicity for the slow acetylators compared to the rapid acetylators . For the CYP2E1 gene , the RsaI polymorphism in the 5 ' untranslated region , and a polymorphic repetitive sequence at the CYP2E1 5'-flaking region were analyzed ; there was no significant association between any CYP2E1 genotype and antituberculosis drug-induced hepatotoxicity . In conclusion , slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatotoxicity ; NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity Background Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury ( DILI ) has not been yet studied . We performed a prospect i ve case-control association study to identify the incidence , pharmacogenetic , pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury ( DILI ) in HIV and tuberculosis ( TB ) co-infected patients . Methods and Findings Newly diagnosed treatment naïve TB-HIV co-infected patients ( n = 353 ) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy , and assessed clinical ly and biochemically for DILI up to 56 weeks . Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2 , CYP2B6 , CYP3A5 , ABCB1 , UGT2B7 and SLCO1B1 genes were done . The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model . The incidence of DILI was 30.0 % , or 14.5 per 1000 person-week , and that of severe was 18.4 % , or 7.49 per 1000 person-week . A statistically significant association of DILI with being of the female sex ( p = 0.001 ) , higher plasma efavirenz level ( p = 0.009 ) , efavirenz/8-hydroxyefavirenz ratio ( p = 0.036 ) , baseline AST ( p = 0.022 ) , ALT ( p = 0.014 ) , lower hemoglobin ( p = 0.008 ) , and serum albumin ( p = 0.007 ) , NAT2 slow-acetylator genotype ( p = 0.039 ) and ABCB1 3435TT genotype ( p = 0.001 ) . Conclusion We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients . Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2 , CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients . Close monitoring of plasma efavirenz level and liver enzymes during early therapy and /or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI BACKGROUND The first line anti-tubercular ( anti-TB ) treatment normally involves isoniazid , rifampicin , pyrazinamide , and ethambutol . Clearance of these drugs depends on the activity of several enzymes such as N-acetyl transferase 2 , cytochrome P450 oxidase and glutathione S-transferase ( GST ) . Some of these enzymes are highly polymorphic leading to significant inter-individual variation in their activity thereby increasing the risk of drug induced hepatotoxicity ( DIH ) . AIM To investigate the possible association of anti-TB DIH with genetic polymorphism of GST genes in Western Indian population . MATERIAL AND METHODS A prospect i ve case-control study was undertaken on patients who received anti-TB treatment . Cases ( n = 50 ) were distinguished from controls ( n = 246 ) based on occurrence of DIH during anti-tubercular treatment . A multiplex polymerase chain reaction was employed to identify homozygous null mutation at GSTM1 and GSTT1 loci . Results . Homozygous null mutation in GSTM1 gene alone or in both 
    Output:
    
ATDILI is more likely to occur in patients with NAT2 slow acetylator genotype , CYP2E1 RsaI/PstI c1/c1 genotype and GSTM1 null genotype .