Immunology demystified: A guide for transplant hepatologists

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

Importance of genetic polymorphisms in liver transplantation outcomes

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.

Pre-and intraoperative predictors of acute kidney injury after liver transplantation

BACKGROUND Acute kidney injury(AKI)after liver transplantation(LT)is a frequent and multifactorial event related to increased morbidity and mortality.Risk factors for AKI after LT still need to be clarified.AIM To identify the predictors of acute kidney injury after liver transplantation.METHODS The frequency and pre-and intraoperative predictors of AKI within the first 7 d after LT were evaluated in adult liver transplant candidates in a single LT center in Croatia.AKI was defined according to the Kidney Disease:Improving Global Outcomes criteria.RESULTS Out of 205 patients(mean age 57±10 years;73.7%males,52.7%with alcoholrelated liver disease)93(45.36%)developed AKI,and the majority of them(58.06%)had stage 1.Only 5.38%of patients required renal replacement therapy after LT.The majority of patients(82.8%)developed AKI within the first two days after the procedure.Multivariate logistic regression identified pre-LT body mass index(OR=1.1,95%CI:1.05-1.24)and red blood cell transfusion(OR=1.66,95%CI:1.09-2.53)as independent predictors of early post-LT AKI occurrence.30-d survival after LT was significantly better for patients without AKI(P=0.01).CONCLUSION Early AKI after LT is a frequent event that negatively impacts short-term survival.The pathogenesis of AKI is multifactorial,but pre-LT BMI and intraoperative volume shifts are major contributors.