AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant reci...AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.展开更多
Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contri...Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes.Determination of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant approach.To provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration variability.Reviewed studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration variability.They also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant complications.However,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these limitations.Furthermore,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association approach.Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.展开更多
基金Supported by Key Technology Support Program of Sichuan ProvinceNo.2013SZ0023
文摘AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.
基金the Croatian Science Foundation grant“The Role of Notch Signalling Pathway in Pathogenesis of Hepatic Fibrosis”,No.UIP-2017-05-1965.
文摘Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes.Determination of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant approach.To provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration variability.Reviewed studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration variability.They also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant complications.However,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these limitations.Furthermore,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association approach.Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.
