摘要
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.
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 CYP3 A5 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.
基金
the Croatian Science Foundation grant“The Role of Notch Signalling Pathway in Pathogenesis of Hepatic Fibrosis”,No.UIP-2017-05-1965.
