As a result, the ABCC2 rs3740065 genotype, sex, and the baseline level of alanine aminotransferase are independent risk factors of antituberculosis drug-induced hepatotoxicity, with P values of .008, .014, and <.001, respectively.
However, miR-122-5p, -192-5p, -34a-5p and -22-3p demonstrated a much more significant induction in patients with hepatocellular DILI, thus revealing better specificity for hepatocellular damage.
Increased expression of CYP2E1 may represent the main factor contributing to oxidative stress-mediated liver damage in drug-induced liver injury (DILI).
As a result, the ABCC2rs3740065 genotype, sex, and the baseline level of alanine aminotransferase are independent risk factors of antituberculosis drug-induced hepatotoxicity, with P values of .008, .014, and <.001, respectively.
Incorporating other mechanisms (reactive metabolite and cytotoxic metabolite generation and hepatic efflux transport inhibition, other than BSEP) to the HRM had minimal beneficial impact in DILI prediction/stratification.
We present a quantitative and mechanistic risk assessment for candidate nomination using data from <i>in vitro</i> assays (hepatic spheroids, BSEP, mitochondrial toxicity, and bioactivation), together with physicochemical (cLogP) and exposure (Cmax<sub>total</sub>) variables from a chemically diverse compound set (33 no/low-, 40 medium-, and 23 high-severity DILI compounds).
Interestingly, further experiments with serum from rats with bile duct ligation (BDL)-induced liver disease indicated that Aldh1a1 and Adh1 are not detectable in serum in cholestasis and may therefore be specific for hepatocellular injury and possibly even drug-induced liver injury (DILI), in particular.
Interestingly, further experiments with serum from rats with bile duct ligation (BDL)-induced liver disease indicated that Aldh1a1 and Adh1 are not detectable in serum in cholestasis and may therefore be specific for hepatocellular injury and possibly even drug-induced liver injury (DILI), in particular.
We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI-DILI; however, no significant difference existed after Bonferroni correction.
Subset analysis of NAT2 acetylator status and severity grade confirmed these results in AT-DILI patients with more severe disease whereas fast and intermediate acetylator phenotypes were associated with a decreased AT-DILI risk.
Using these data, we derived a novel parameter, P<sub>ALT</sub> = ALT_AUC*Peak ALT<sup>0.18</sup> /10<sup>5</sup> ((IU/L)<sup>2</sup> *h), where AUC is area under the curve, that correlated well with hepatocyte loss estimates derived by DILIsym in patients with DILI due to six different hepatotoxic drugs.
Cytochrome P450 2E1 (CYP2E1) plays a vital role in drug-induced hepatotoxicity and cancers (e.g. lung and bladder cancer), since it is responsible for metabolizing a number of medications and environmental toxins to reactive intermediate metabolites.
RUCAM criteria were defined as the gold standard, and the other two criteria were as follows: 1) ALT or aspartate aminotransferase (AST) levels greater than 5 × the ULN on two consecutive occasions and/or ALP levels greater than 2 × the ULN on two consecutive occasions [issued by DILI Network (DILIN)]; 2) ALT levels greater than 1 × the ULN on two consecutive occasions or ALT levels greater than 2 × the ULN [issued by the National Medical Products Administration (NMPA) of China].
We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non-HLA signals for any penicillin-relatedDILI.
Previous studies suggest that individuals who are homozygous-null at the GSTM1 or GSTT1 locus may have an increased risk of environmentally related cancers and drug-induced hepatotoxicity.
Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event.
Volatile anaesthetics are known to cause drug-induced liver injury, a hepatotoxic reaction characterised by antibodies to trifluoroacetylated lipid and protein adducts and cytochrome p450 2E1.
In the pilot study, the frequency of HLA-B*35:01 was 45.4% in PM-DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7-77.8; P = 1.9 × 10<sup>-10</sup> ).
Changes in the serum alanine aminotransferase (ALT) concentrations after starting corticosteroid treatment were determined and compared between the DILI and AIH groups.