Objective To observe efficacy of rapamycin combined with sorafenib in hepatocellular carcinoma (HCC) patients with tumor recurrence after liver transplantation beyond Milan criteria. Methods Forty-one beyond Milan criteria HCC patients who underwent the classic orthotopic liver transplantation without bypass and the tumor postoperatively recurred in the Tianjin First Center Hospital from February 1, 2012 to August 31, 2015 were collected retrospectively, then were divided into a local treatment group (n=21) and a comprehensive treatment group (n=20). The local treatment included the surgical resection, radiofrequency ablation, transcatheter arterial chemoembolization, radioactive seed implantation, etc.. The comprehensive treatment was on the basis of the local treatment plus rapamycin in combination with sorafenib. Results There were 12 patients with stable disease and 9 patients with progressive disease in the local treatment group. There were 12 patients with partial response, 10 patients with stable disease and 8 patients with progressive disease in the comprehensive group. In the local treatment group and the comprehensive treatment group, the median survival time were 9 months and 12 months, and the 1-year and 2-year survival rates after the recurrence were 14% versus 55%, 0 versus 15%, respectively. The survival of the comprehensive treatment group was significantly better than that of the local treatment group (P<0.01). Conclusion Combination of rapamycin and sorafenib in HCC patients with tumor recurrence after liver transplantation beyond Milan criteria can significantly improve survival time of patient with recurrence.
ObjectiveTo investigate the relationship between the CYP3A5 genotyping and the drug metabolism of tacrolimus after operation in adult liver transplantation.MethodsNinety-eight adult patients with liver transplantation in Tianjin First Center Hospital were selected as subjects. The blood samples of liver transplantation recipients and donor were collected before operation, and then tested the CYP3A5 genotyping by PCR method. The weekly body mass, tacrolimus dose, and drug valley concentration of the patients were monitored in 1, 2, 3, and 4 weeks after operation, to calculate the tacrolimus concentration/dose ratio. And then compared the effects of different genotyping of donor and receptors on tacrolimus concentration/dose ratio.ResultsIn the CYP3A5 genotyping of 98 patients with liver transplantation and the corresponding donors, GG type was the most and AA type was the least, the distribution of alleles was in accordance with the genetic law, and the difference was not statistically significant (P>0.05). According to the donor genotype, the results showed that there was a significant correlation between tacrolimus concentration/dose ratio and donor or recipients CYP3A5 genotype at 1, 2, 3, and 4 weeks after liver transplantation, and there was significant difference among the three groups (P<0.05): GG>AG>AA. According to the combined grouping of donor and receptor genotype, the results showed that there was significant difference in tacrolimus concentration/dose ratio among A*/A*, A*/GG, GG/A*, and GG/GG group (P<0.05), while there was significant difference in tacrolimus concentration/dose ratio between GG/GG and A*/A* group (P<0.01), the tacrolimus concentration/dose ratio was highest in GG/GG group and lowest in A*/A* group.ConclusionsThe CYP3A5 genotyping of the recipient and donor can affect the blood concentration of tacrolimus after liver transplantation, and the CYP3A5 GG genotype is more likely to reach the target plasma concentration than the other genotypes, that the detection of donor and recipient CYP3A5 genotype in patients with liver transplantation can provide a reference for individualized treatment of tacrolimus after liver transplantation.