Hepatic miR-301a as a Liver Transplant Rejection Biomarker? And Its Role for Interleukin-6 Production in Hepatocytes.
BACKGROUND New graft cytochrome P450 2C19 (CYP2C19) should have different characteristics after living-donor liver transplantation (LDLT). We prospectively investigated the influence of genotypes of CYP2C19 in liver graft pathological finding (GPF) and postoperative liver function (POLF) of recipients after LDLT. MATERIAL/METHODS Among 60 consecutive patients who underwent LDLT, 36 recipients developed sudden-onset abnormal liver function and required liver biopsy, while the remaining 24 recipients did not require biopsy. LDLT recipient blood samples were genotyped for CYP2C19 variants, and recipients were categorized as homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers (HetEM), and poor metabolizers (PM). RESULTS The acute rejection rate was 15.0% (9/60). There were 4 characteristics of GPF when abnormal POLF occurred. Logistic regression analysis showed that the risk estimate of abnormal POLF was 26.7 times higher for LDLT recipients with the CYP2C19 HomEM genotype as compared to the PM genotype, and 5.0 times higher for LDLT recipients with the HomEM genotype as compared to the HetEM genotype. A linear trend relationship was found between the incidence of abnormal POLF and the CYP2C19 genotype. CONCLUSIONS These results suggest that the speed of drug metabolism as characterized by the CYP2C19 genotype (HomEM > HetEM > PM) may affect the outcome after LDLT; thus, CYP2C19 genotyping may be valuable for predicting abnormal POLF with different GPF after LDLT.