The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI).
Certain serum biomarkers, like miR-122, may have clinical utility in early-presenting patients with either intrinsic or idiosyncratic DILI in the future, while others likely will not find use.
Sensitivity of miR-122 in diagnosing DILI was [0.85 (95% CI, 0.75-0.91), I = 53.46%] and specificity was [0.93 (95% CI, 0.86-0.97), I = 65.10%], the area under ROC curve was 0.95 (95% CI, 0.93-0.97).
Furthermore, the proposed biosensor exhibited excellent specificity and recovery in spiked serum samples, and was successfully used for detecting miR-122 in real biological samples, which provided a rapid and efficient method for detecting drug-induced liver injury at an early stage.
For example, in an acetaminophen (APAP)-induced hepatocellular injury model, plasma let-7b-5p was up-regulated as early as 3 h after dosing, whereas a significant change in ALT level was observed at 12 h. We then focused on the DILI type-specific miRNAs in plasma that were up-regulated at the early stage of injury.
Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI.
Two SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30-44.70), 0.10 (0.03-0.33) and 9.98 (3.32-33.80), respectively).
A significant association was noted between HLA-B∗35:02 and risk for minocycline DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6, 95% CI: 7.8-89.8, p=2.5×10<sup>-8</sup>).
FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI.
We were also able to demonstrate that, although miR-122 is present in greater quantities in exosome-free form, both exosome-bound and non-vesicle bound miR-122 are released in a similar profile throughout the course of DILI.
In a multivariate logistic analysis, the proportion of patients carrying <i>HLA-B</i><sup>*</sup><i>57</i> (<i>P</i> = 0.002) and <i>HLA-B</i><sup>*</sup><i>14</i> (<i>P</i> = 0.014) alleles were significantly higher in DILI cases compared with treatment tolerants.
Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies.
In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.