Anti-tuberculosis Drug-induced Liver Injury Research Articles

Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study.

The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population. A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes. 224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5μmol/L vs. 15.0μmol/L vs. 13.7μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively). Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.

Comment on -Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Comment on -Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Incidence, outcomes, and risk factors of antituberculosis drugs induced liver injury in Thailand: A retrospective cohort study

Incidence, outcomes, and risk factors of antituberculosis drugs induced liver injury in Thailand: A retrospective cohort study

Therapeutic potential of Shaoyao Gancao Decoction in mitigating anti-tuberculosis drug-induced liver injury through Nrf-2/HO-1/NF-κB signaling.

Tuberculosis (TB) is a persistent global health issue, evidenced by an increasing number of cases. Although anti-TB drugs have proven efficacy, they are often associated with severe liver injury (ATB-DILI). The objective of this research was to uncover the mechanisms through which Shaoyao Gancao Decoction (SGD) mitigates ATB-DILI, emphasizing the role of the Nrf-2/HO-1/NF-κB signaling pathway. We prepared SGD granules and subjected them to HPLC-MS/MS for analysis. An ATB-DILI rat model was then developed and administered SGD. We evaluated liver injury markers, the extent of oxidative stress, inflammation, and the principal proteins involved in the Nrf-2/HO-1/NF-κB pathway. Additionally, network pharmacology techniques were utilized to discern potential SGD targets and their associated pathways. Administering SGD had a notable effect in counteracting the elevation of liver injury markers and pathological alterations induced by ATB-DILI. Moreover, there was a marked reduction in oxidative stress and inflammation in the treated rats. We identified 12 active compounds in SGD, with 88 shared targets between SGD and ATB-DILI. Subsequent KEGG analysis brought attention to pathways like MAPK, NF-κB, and IL-17 signaling. Our findings pave the way for more in-depth studies into the application of SGD in treating drug-induced liver injuries.

Association of Gene Polymorphisms and Serum Levels of ALAS1 with the Risk of Anti‐Tuberculosis Drug‐Induced Liver Injury

AbstractThe accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti‐tuberculosis drug‐induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate‐limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case‐control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360‐5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk.

Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Antituberculosis drug-induced liver injury (ATDILI) is a significant problem of tuberculosis treatment. This systematic review and meta‑analysis aimed at evaluating the incidence and risk factors of ATDILI in adult patients with tuberculosis in India. Five electronic databases were searched comprehensively for studies on Indian adult patients with tuberculosis investigating the incidence and/or risk factors of ATDILI. The relevant data was pooled in a random or fixed-effect model to calculate the pooled incidence with a 95% confidence interval (CI), standardized mean difference (MD) or odds ratio (OR). Following the screening of 3221 records, 43 studies with 12,041 tuberculosis patients were finally included. Based on the random effect model, the pooled incidence of ATDILI was 12.6% (95% CI, 9.9-15.3%, p < 0.001, I2 = 95.1%). The pooled incidence was higher in patients with daily treatment regimen compared to the thrice weekly regimen (16.5% vs. 3.5%). The concurrent hepatitis B or C infection, alcohol consumption and underlying chronic liver disease were associated with high incidence of ATDILI. The pooled incidence of acute liver failure (ALF) among ATDILI patients was 6.78% (95% CI 3.9-9.5%). Female gender (OR 1.24), older age (MD 0.26), lean body mass index (OR 3.8), hypoalbuminemia (OR 3.09), N-acetyltransferase slow acetylator genotypes (OR 2.3) and glutathione S-transferases M null mutation (OR 1.6) were found to be associated with an increased risk of ATDILI. The pooled mortality rate of ATDILI patients was 1.72% (95% CI 0.4-3.0%) overall and 71.8% (95% CI 49.3-94.2%) in case of ALF. Overall, 12.6% patients of tuberculosis in India developed ATDILI when combination of first-line antituberculosis drugs was used. An average of 7% of ATDILI patients progressed to ALF which had a high mortality rate. Older age, female, poor nutritional status and some genetic polymorphisms were identified as significant risk factors.

The Feasibility of using Liver Function Indices and FibroScan in combination to predict the occurrence of anti-tuberculosis drug-induced liver injury in patients with liver disease

Background: The study aims to assess the feasibility of using a combined approach of liver function indices and FibroScan measurements as a predictive tool for the early detection of anti-tuberculosis drug-induced liver injury (DILI) in patients with existing liver disease. Methods: A retrospective cohort study was conducted, including adult tuberculosis patients with documented liver disease. Liver function was assessed using standard biochemical parameters, and FibroScan examinations were performed to determine liver stiffness measurement (LSM). Patients were monitored for clinical and biochemical signs of DILI throughout treatment. Logistic regression models and Receiver Operating Characteristic (ROC) curves were used for data analysis. Statistical significance was set at p &lt; 0.05. Results: Patients who developed DILI showed significantly higher levels of ALT, AST, total bilirubin, GGT, and LSM, with strong positive correlations between these markers and DILI occurrence. Logistic regression analysis revealed elevated ALT, AST, TBIL, and GGT were strongly associated with an increased likelihood of DILI. The area under the ROC curves indicated excellent predictive accuracy of these parameters. A nomogram for predicting DILI based on the combined biomarkers was established. Conclusion: The study demonstrates the feasibility of utilizing liver function indices and FibroScan measurements in combination to predict anti-tuberculosis DILI. The results highlight the importance of baseline liver health assessment and offer promising implications for clinical practice, aiding in individualized risk estimation and therapeutic decision-making for patients with liver disease initiating anti-tuberculosis therapy. Further validation in larger cohorts is warranted to strengthen the predictive model.

Clinical risk factors for moderate and severe antituberculosis drug-induced liver injury.

To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

Association of DNA methylation, polymorphism and mRNA level of ALAS1 with antituberculosis drug-induced liver injury.

Aim: To investigate the association of DNA methylation, genetic polymorphisms and mRNA level of aminolevulinate synthase 1 (ALAS1) with antituberculosis drug-induced liver injury (AT-DILI) risk.Methods: Based on a 1:1 matched case-control study with 182 cases and 182 controls, one CpG island and three single nucleotide polymorphisms (SNPs) were detected. ALAS1 mRNA level was detected in 34 samples.Results: Patients with methylation status were at high risk of AT-DILI (odds ratio: 1.567, 95% CI: 1.015-2.421, p =0.043) and SNP rs352169 was associated with AT-DILI risk (GA vs. GG, odds ratio: 1.770, 95% CI: 1.101-2.847, p=0.019). ALAS1 mRNA level in the cases was significantly lower than that in the controls (0.75±0.34 vs. 1.00±0.42, p =0.021).Conclusion: The methylation status and SNP rs352169 of ALAS1 were associated with AT-DILI risk.

Longitudinal metabolomics of human plasma reveal metabolic dynamics and predictive markers of antituberculosis drug-induced liver injury

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

Progress in novel biomarkers of anti-tuberculosis drug-induced liver injury

Anti-tuberculosis drug-induced liver injury(ATB-DILI) is the most common adverse reaction during anti-tuberculosis therapy in tuberculosis patients. At present, the diagnosis of ATB-DILI is mainly based on traditional biomarkers such as transaminases, but these indicators have low specificity for liver toxicity, they cannot explain the mechanism of liver injury and the early onset of ATB-DILI. Based on the prediction of disease severity, treatment and prevention, this paper described the current potential biomarkers of ATB-DILI.

The hsa_circ_0082152 maintains NF-κB mRNA stability by binding to MTDH to promote anti-tuberculosis drug-induced liver injury

Anti-tuberculosis drug-induced liver injury (ADLI) is a common adverse reaction during anti-tuberculosis treatment and often leads to treatment interruptions. Circular RNAs (circRNAs) have been identified as key modulators in liver diseases. CircRNAs is a special class of noncoding RNAs that have been found to have significant impacts on the progression of inflammation via various mechanisms. In the serum of ADLI patients, upregulation of the circular RNA hsa_circ_0082152 (derived from the host gene snd1) was observed, along with increased ALT and AST levels, as well as alterations in the levels of inflammation-related factors such as NF-κB, IL-1β and TNF-α. To elucidate the underlying mechanisms, we established an HL-7702-ADLI cell model and confirmed similar upregulation of hsa_circ_0082152. Downregulation of hsa_circ_0082152 significantly inhibited inflammatory injury in ADLI cells, while upregulation had the opposite effect. RNA immunoprecipitation showed that hsa_circ_0082152 functions by interacting with metadherin (MTDH). Our study further verified that the interaction of hsa_circ_0082152 with the MTDH protein binding to NF-κB mRNA to maintain NF-κB mRNA stability, which increases the expression of NF-κB and its targets IL-1β and TNF-α. Conversely, depletion of MTDH rescued the promotive effect of hsa_circ_0082152 overexpression on ADLI inflammation. Therefore, hsa_circ_0082152 overexpression promotes ADLI progression via the MTDH/NF-κB axis.

The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study

BackgroundTuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. MethodsWe conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan–Meier analysis, and Cox proportional hazards models. ResultsA total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan–Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose–response relationship against the DILI. ConclusionStatin treatment had a protective effect against the risk of anti-TB DILI with a positive dose–response relationship.

Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective.

Genetic polymorphisms can exert a considerable impact on drug pharmacokinetics (PK) and the development of adverse drug reactions (ADR). However, the effect of genetic polymorphisms on the anti-tuberculosis (anti-TB) drug, and particularly rifampicin (RIF), exposure or anti-TB drug-induced liver injury (DILI) remains uncertain. Here, we evaluated the relationship between single nucleotide polymorphisms (SNPs) detected in the RIF pharmacogenes (AADAC, SLCO1B1, SLCO1B3, ABCB1, and NR1I2) and RIF PK parameters, as well as anti-TB treatment-associated DILI. In total, the study enrolled 46 patients with drug-susceptible pulmonary TB. The RIF plasma concentration was measured using the LC-MS/MS method in the blood samples collected pre-dose and 2 and 6 h post-dose, whilst the DILI status was established using the results from blood biochemical analysis performed before and 10-12 days after treatment onset. The genotyping was conducted using a targeted NGS approach. After adjustment for confounders, the patients carrying the rs3732357 GA/AA genotype of the NR1I2 gene were found to have significantly lower RIF plasma AUC0-6 h in comparison to those with GG genotype, while the difference in RIF plasma Cmax was insignificant. None of the analyzed SNPs was related to DILI. Hence, we are the first to report NR1I2 intronic SNP rs3732357 as the genetic component of variability in RIF exposure. Regarding anti-TB treatment-associated DILI, the other preexisting factors promoting this ADR should be considered.

Changing Trajectories of Alanine Aminotransferase and Risk of Antituberculosis Drug-Induced Liver Injury in Chinese Patients: A Cohort Study.

Antituberculosis drug-induced liver injury (ATLI) is a major adverse effect during antituberculosis treatment. Early detection or prediction is essential to prevent ATLI in antituberculosis treatment patients. The purpose of this work is to explore the relationship between alanine aminotransferase (ALT) trajectories within 15 days of initial treatment and the risk of ATLI. Based on a historical cohort of patients hospitalized for antituberculosis treatment and group-based trajectory modeling analysis, ALT trajectories within 15 days of initial treatment were determined. Conditional logistic regression model was used to estimate the association between different ALT trajectories and the risk of ATLI, and the corresponding odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with covariates. Based on the ALT levels within 15 days of initial treatment, a total of 853 patients were divided into four ALT trajectories. The incidence of ATLI significantly increased with the increase of ALT trajectories (2.33%, 4.38%, 5.90%, and 2.44%, respectively). Compared with trajectory 1, the adjusted OR for ATLI in trajectory 2, trajectory 3, and trajectory 4 were 2.448 (95% CI: 0.302-19.856, P = 0.402), 5.373 (95% CI: 0.636-45.411, P = 0.123), 11.010 (95% CI: 0.720-168.330, P = 0.085), respectively, and there was an increasing trend of ATLI risk (Ptrend = 0.015). Different ALT trajectories within 15 days of initial treatment were associated with different risk of ATLI, and it is necessary to pay attention to the ALT trajectory within 15 days of initial treatment to predict the occurrence of ATLI.

Efficacy and safety of bicyclol for treating patients with antituberculosis drug-induced liver injury.

BACKGROUND: Bicyclol was used for treating idiosyncratic acute drug-induced liver injury (DILI) in a phase II trial. This study was aimed at evaluating the efficacy and safety of bicyclol 25 and 50 mg thrice a day (TID) for treating acute DILI caused by anti-TB drugs in the light of the trial results.METHODS: We analysed clinical data of patients with TB drug-induced DILI in the trial database. The primary endpoint was reduction in serum alanine aminotransferase (ALT) levels after 4 weeks of treatment compared to baseline.RESULTS: Overall, 148 patients were included, with respectively 48, 52 and 48 patients included in the control (456 mg polyene phosphatidylcholine TID), high-dose (50 mg bicyclol TID) and low-dose (25 mg bicyclol TID) groups. ALT levels decreased by respectively â-"149.0 (IQR â-"299.3 to â-"98.3 (), â-"225.5 (IQR â-"309.3 to â-"181.8 ) and â-"242.5 (IQR â-"364.8 to â-"153.8) U/L in the control, high-dose and low-dose groups (P < 0.001). The ALT normalisation rates at weeks 1, 2, 4, 6 and 8 were higher in the high- and low-dose groups, while adverse events and serious adverse events were similar across groups.CONCLUSIONS: Bicyclol (25 and 50 mg TID) is effective and safe in treating anti-TB DILI, and bicyclol 50 mg TID showed higher efficacy.

Relevance of NAT2 genotype and clinical factors to risk for antituberculosis drug-induced liver injury.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing ofantituberculosis(ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB;p<0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p<0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

Systematic review and network meta-analysis of efficacy and safety of interventions for preventing anti-tuberculosis drug induced liver injury

Anti-tuberculosis drug induced liver injury (Anti-TB DILI) is the most common adverse events (AEs) necessitating therapy interruption but there is no preventing regimen. This study aimed to examine the efficacy and safety of herbs/alternative medicines for preventing anti-TB DILI. Relevant articles were identified through a systematic search in 5 international databases from inception till March 2022. All randomized controlled trials (RCT) assessing the effects of herbal or alternative medicines against anti-TB DILI were included. The network meta-analysis (NMA) was used to synthesize the evidence for preventing hepatotoxicity using a random-effects model. A total of 3423 patients from 14 RCTs were included. The NMA indicated that supplementation of Turmeric plus Tinospora cordifolia (RR 0.07; 95% CI 0.02 to 0.28), and N-acetyl cysteine (NAC) (RR 0.09; 95% CI 0.01 to 0.75) significantly reduced the incidence of anti-TB DILI compared with placebo. In addition, poly herbal product significantly reduced alkaline phosphatase (ALP) (MD − 21.80; 95% CI − 33.80 to − 9.80) and total bilirubin (Tbil) compared with placebo (MD − 0.51; 95% CI − 0.76 to − 0.26). There was no statistically significant difference in the occurrence of AEs in any intervention. In conclusion, Turmeric plus Tinospora cordifolia, NAC and poly-herbal product may provide benefit for preventing anti-TB DILI in TB patients. However, these findings are based on a small number of studies. Additional studies are warranted to confirm the findings.

Genetic Polymorphisms of UDP-Glucuronosyltransferases and Susceptibility to Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis.

The PRISMA statement was strictly followed, and the protocol was registered in PROSPERO (CRD42022339317). The PICOS framework was used: patients received antituberculosis treatment, UGTs polymorphisms (mutants), UGTs polymorphisms (wild), AT-DILI, and case-control studies. Eligible studies were searched through nine databases up to April 27, 2022. The study's qualities were assessed by the revised Little's recommendations. Meta-analysis was conducted with a random-effects model using odds ratios (ORs) with 95% confidence intervals (95% CIs) as the effect size. Twelve case-control studies with 2128 cases and 4338 controls were included, and 32 single nucleotide polymorphisms (SNPs) in the seven UGT genes have been reported in Chinese and Korean. All studies were judged as high quality. The pooled results indicated that UGT1A1 rs3755319 (AC vs. AA, OR = 1.454, 95% CI: 1.100-1.921, P = 0.009), UGT2B7 rs7662029 (G vs. A, OR = 1.547, 95% CI: 1.249-1.917, P < 0.0001; GG + AG vs. AA, OR = 2.371, 95% CI: 1.779-3.160, P < 0.0001; AG vs. AA, OR = 2.686, 95% CI: 1.988-3.627, P < 0.0001), and UGT2B7 rs7439366 (C vs. T, OR = 0.585, 95% CI: 0.477-0.717, P < 0.0001; CC + TC vs. TT, OR = 0.347, 95% CI: 0.238-0.506, P < 0.0001; CC vs. TC + TT, OR = 0.675, 95% CI: 0.507-0.898, P = 0.007) might be associated with the risk of AT-DILI. The polymorphisms of UGT1A1 rs3755319, UGT2B7 rs7662029, and UGT2B7 rs7439366 were significantly associated with AT-DILI susceptibility. However, this conclusion should be interpreted with caution due to the low number of studies and the relatively small sample size.

HLA-DQB1*05:02 Allele Association with Anti-Tuberculosis Drug Induced Liver Injury: A Single-Hospital Based Study in Jakarta, Indonesian Population

Past studies have delved into the genetic factors underlying anti-tuberculosis drug-induced liver injury (AT-DILI), primarily concentrating on polymorphisms in genes responsible for drug-metabolizing enzymes. However, the immune system's potential impact on drug adverse effects, specifically through genes such as HLA, has received limited attention. Previous research has notably revealed an association between HLA-DQB1*05 and AT-DILI, specifically the prevalence of the HLA-DQB*05:02 allele in AT-DILI patients. In light of this, our study aimed to investigate a potential link between HLA-DQB1*05:02 alleles and AT-DILI. In this study, we included 51 AT-DILI cases and 59 controls belonging to the Javanese ethnic group. The HLA-DQB1*05:02 genotypes were determined using a customized PCR-based typing method, and the results were further confirmed by analyzing five samples via the Luminex assay. Our findings revealed a significant association between HLA-DQA1*05: 02 and the risk of AT-DILI (P = 0.022; OR (95% CI) = 6.11 (1.25-29.74)). Moreover, the consistent results obtained from the Luminex assay validated the reliability of the custom PCR-based genotyping approach. This preliminary study sheds light on the relationship between the HLA-DQB1*05:02 allele and AT-DILI within the Indonesian population. Furthermore, our study demonstrates the dependability of custom PCR-based genotyping in detecting HLA-DQB1*05:02 alleles. Nevertheless, further research is imperative to corroborate and expand upon our findings.