Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice

Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice

Liver failure in patients with obstructive jaundice is a significant contributor to mortality within this patient cohort. The exact mechanism and triggers of this occurrence are yet to be fully understood. With this in mind, our study aimed to assess the correlation between the urinary 6 β-OHC/C rat...

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Published in:Free radical biology & medicine Vol. 208; pp. 229 - 235
Main Authors: Lebedev, Sergey S., Tavobilov, Mikhail M., Karpov, Alexey A., Abramov, Kirill A., Bochkov, Pavel O., Shevchenko, Roman V., Denisenko, Natalia P., Shabunin, Alexey V., Sychev, Dmitri A.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-11-2023
Subjects:
CYP3A4 cytochrome activity
Obstructive jaundice
Obstructive jaundice
CYP3A4 cytochrome activity
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Summary:Liver failure in patients with obstructive jaundice is a significant contributor to mortality within this patient cohort. The exact mechanism and triggers of this occurrence are yet to be fully understood. With this in mind, our study aimed to assess the correlation between the urinary 6 β-OHC/C ratio and various biochemical parameters of liver function. Furthermore, we conducted genotyping of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) polymorphic markers to investigate the potential effects of their variants on the probability of liver failure in obstructive jaundice. Our study included 75 patients diagnosed with severe obstructive jaundice. All test subjects underwent functional liver tests, and control blood tests were administered on the seventh day following biliary decompression. Patients were categorized into two groups: group 1 - patients without liver failure (n = 60) and group 2 - patients with liver failure (n = 15). Laboratory indexes such as 6 β –OHC concentration and 6 β- OHC/cortisol ratio can serve as significant predictors of liver failure in patients with moderate and severe degree obstructive jaundice after biliary decompression. Based on the study of “wild” and polymorphic variants of CYP3A4*22 (CC and CT) and polymorphism of CYP3A5*3A6986G (GG, GA, AA), it was discovered that liver failure in the CYP3A4*22 variant may be associated with the CC genotype, and in the CYP3A5*3 variant - with the GA genotype. Hence, the determination of 6β- OHC concentration and 6β- OHC/C ratio, as well as the analysis of polymorphic and “wild” variants of CYP3A4*22 (CC and CT) and CYP3A5*3 polymorphism A6986G (GG, GA, AA), may play a crucial role in predicting liver failure in patients with obstructive jaundice. [Display omitted] •Decrease in activity of CYP3A in patients with obstructive jaundice can lead to liver failure.•Determination of 6β- OHC concentration and 6β- OHC/C ratio may be used for prediction of liver failure.•Study of polymorphic and “wild” variants of CYP3A4*22 (CC and CT) and CYP3A5*3 polymorphism A6986G (GG, GA, AA) is important in patients with obstructive jaundice.
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ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2023.08.012