scholarly journals Clinical utility of ABCB1 single nucleotide polymorphism on tacrolimus dose requirements in Egyptian liver transplant patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Azza Abd El-rahman Saab ◽  
Eman Saleh El-hadidi ◽  
Maha Mohsen Hussein ◽  
Maram Saeed Abd El-baki Shararah ◽  
Heba Hassan Aly

Abstract Background Liver transplantation (LT) is the only effective radical cure for all types of end-stage liver diseases. Major advances have been made in the field of liver transplantation due to improvements in surgical techniques and organ conservation as well as optimization of intensive care and immunosuppressive management. We aimed to assess the influence of ABCB1 gene polymorphism of liver transplant recipients on blood level and dose requirements of oral tacrolimus, in an attempt to help in designing an individualized tacrolimus regimen for Egyptian liver transplant recipient. The study included 25 liver transplant recipients and their respective 25 donors. All subjects of this study were subjected to full medical history, clinical evaluation, laboratory investigations, and ABCB1 gene polymorphism evaluation by RT-PCR. Tacrolimus concentration was evaluated for all the recipients during the first 3 months post transplantation. Results The present study revealed that the presence of CC genotype was significantly correlated to the effect on tacrolimus C/D ratio and weight-adjusted tacrolimus dose during the first week of the first and 2nd months (Z = −2.108, P <0.05) but not the 3rd month post transplantation (p-value >0.05). Subjects carrying CC genotype required higher doses of tacrolimus to achieve the desired trough levels compared to subjects carrying CT and TT genotypes. The same effect was observed over the whole period of the study but the results were statistically non-significant (p-value>0.05). Recipients who received liver tissue from donors carrying CC genotype also required higher doses of tacrolimus and reached lower levels of blood tacrolimus trough levels. Conclusion The present study revealed that ABCB1 CC genotype of both recipients and donors of liver transplantation was significantly associated with increased required tacrolimus dose early after liver transplantation reaching statistically significant level in the first week of the first and second months.

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Fahad Azam ◽  
Moosa Khan ◽  
Tanwir Khaliq ◽  
Abubakar Hafeez Bhatti

Objective: To evaluate the possible association of ABCB1 single nucleotide polymorphism (SNPs) of the ABCB1 gene with tacrolimus dosages, concentration-to-dose ratios (CDR) and adverse effects in Pakistani liver transplant recipients. Methods: This observational study was conducted at Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi from September 2016 to July 2020. Eighty-one liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Transplant recipients were genotyped for three ABCB1 SNPs (rs1045642, rs2032582 and rs1128503). Acute cellular rejection (ACR), sepsis and other adverse events were monitored. Results: ABCB1 rs1045642 CC genotype showed lower tacrolimus CDR as compared to CT and TT genotype in the first week of the post-transplantation period (p=0.02). There was a significant association of polymorphisms in rs1045642, rs2032582 and rs1128503 with psychosis, sepsis and ACR respectively. Conclusion: Identification of ABCB1 rs1045642 polymorphism may shorten the time to achieve optimum levels of tacrolimus during dose titration. ABCB1 polymorphism rs1045642, rs2032582 and rs1128503 may predict adverse effects in liver transplant recipients receiving tacrolimus. doi: https://doi.org/10.12669/pjms.37.3.3898 How to cite this:Azam F, Khan M, Khaliq T, Bhatti ABH. Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3898 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2020 ◽  
pp. 088506662093244
Author(s):  
Justin K. Lui ◽  
Lidia Spaho ◽  
Shahrad Hakimian ◽  
Michael Devine ◽  
Rosa Bui ◽  
...  

Introduction: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation. Methods: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed. Results: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not. Conclusions: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.


2021 ◽  
Author(s):  
Juhan Lee ◽  
Jae Geun Lee ◽  
Shin Hwang ◽  
Kwang-Woong Lee ◽  
Jong Man Kim ◽  
...  

Abstract Background and aims: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. Methods: This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19–42).Results: A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; P = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Renal dysfunction after liver transplantation was independently associated with increased mortality.Conclusions: In this nationwide study, use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.


2021 ◽  
Vol 8 ◽  
pp. 205435812110297
Author(s):  
Jean Maxime Côté ◽  
Isabelle Ethier ◽  
Héloïse Cardinal ◽  
Marie-Noëlle Pépin

Background: Chronic kidney disease following liver transplantation is a major long-term complication. Most liver transplant recipients with kidney failure will be treated with dialysis instead of kidney transplantation due to noneligibility and shortage in organ availability. In this population, the role of peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) remains unclear. Objective: To determine the feasibility regarding safety, technique survival, and dialysis efficiency of PD in liver transplant recipients requiring KRT for maintenance dialysis. Design: Systematic review. Setting: Interventional and observational studies reporting the use of PD after liver transplantation. Patients: Adult liver transplant recipients with kidney failure treated with maintenance KRT. Measurements: Extracted data included eligibility criteria, study design, demographics, and PD modality. The following outcomes of interest were extracted: rate of peritonitis and microorganisms involved, noninfectious peritoneal complications, technique survival, and kidney transplantation-censored technique survival. Non-PD complications included overall survival, liver graft dysfunction, and hospitalization rate. Methods: The following databases were searched until July 2020: MedLine/PubMed, EMBASE, CINAHL, and Cochrane Library. Two reviewers independently screening all titles and abstracts of all identified articles. Due to the limited sample size, observational designs and study heterogeneity expected, no meta-analysis was pre-planned. Descriptive statistics were used to report all results. Results: From the 5263 identified studies, 4 were included in the analysis as they reported at least 1 outcome of interest on a total of 21 liver transplant recipients, with an overall follow-up duration on PD of 19.0 (Interquartile range [IQR]: 9.5-29.5) months. Fifteen episodes of peritonitis occurred in a total cumulative PD follow-up of 514 patient-months, representing an incidence rate of 0.35 per year. These episodes did not result in PD technique failure, mortality, or impairment of liver graft function. Limitations: Limitations include the paucity of studies in the field and the small number of patients included in each report, a risk of publication bias and the impossibility to directly compare hemodialysis to PD in this population. These results, therefore, must be interpreted with caution. Conclusions: Based on limited data reporting the feasibility of PD in liver transplant recipients with kidney failure, no signal was associated with an increased risk of infectious complications. Long-term studies evaluating this modality need to be performed. Registration (PROSPERO): CRD42020218374.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M G Abdelrahman ◽  
H A Mahmoud ◽  
M K Mohsen ◽  
M O Ali ◽  
A M N Mohamed

Abstract Background Liver transplantation is considered to be the only curative treatment for patients with end stage liver disease. Postoperative infection remains to be one of the most common causes of morbidity and mortality throughout the past years. Cytomegalovirus (CMV) infection although considered to be a weak viral infection that usually passes asymptomatic in immunocompetent patients, however, it is considered one of the most common pathogens causing morbidities and mortality in liver transplant recipients. Multiple studies have been done to assess the risk factors for developing CMV infection. Objective Identification of risk factors predicting Cytomegalovirus infection in liver transplant recipients following transplantation. Methods This retrospective study was conducted on 194 patients and their donors who underwent living donor liver transplantation operation at Ain Shams centre for organ transplantation (ASCOT) at Ain Shams specialized hospital in the period between January 2010 and December 2016 with at least one year follow up period after operation for the recipient group. Results In our study, 194 patients undergoing liver transplantation at Ain shams centre for organ transplantation over seven years from January 2010 to December 2016 have been followed to assess risk factors affecting CMV infection development. Chronic rejection was found to be the most common factor associated with CMV infection followed by Cyclosporin (Neoral) as main postoperative immunosuppressant following liver transplantation. Other factors that were found to carry risk for CMV infection included younger age, advanced MELD score, positive CMV IgM status of the donors and recipients. Conclusion Differentiation of Cytomegalovirus disease from Cytomegalovirus infection isn’t always available as it requires tissue invasive techniques. Multiple risk factors have been attributed to cause Cytomegalovirus infection (viremia) . In our study, rejection (chronic rejection) was the factor that carries highest risk for Cytomegalovirus infection development followed by Cyclosporin .


2018 ◽  
Vol 5 ◽  
Author(s):  
Sebastian C. B. Bremer ◽  
Lars Reinhardt ◽  
Michael Sobotta ◽  
Marie C. Hasselluhn ◽  
Thomas Lorf ◽  
...  

2018 ◽  
Vol 102 (5) ◽  
pp. 727-743 ◽  
Author(s):  
Michael Charlton ◽  
Josh Levitsky ◽  
Bashar Aqel ◽  
John OʼGrady ◽  
Julie Hemibach ◽  
...  

2012 ◽  
Vol 26 (9) ◽  
pp. 607-610 ◽  
Author(s):  
Kris P Croome ◽  
Vivian McAlister ◽  
Paul Adams ◽  
Paul Marotta ◽  
William Wall ◽  
...  

BACKGROUND Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further.METHODS: A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed.RESULTS: Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients.CONCLUSIONS: There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.


2020 ◽  
Vol 9 (8) ◽  
pp. 2352
Author(s):  
Cornelius Engelmann ◽  
Martina Sterneck ◽  
Karl Heinz Weiss ◽  
Silke Templin ◽  
Steffen Zopf ◽  
...  

Human cytomegalovirus (CMV) remains a major cause of mortality and morbidity in human liver transplant recipients. Anti-CMV therapeutics can be used to prevent or treat CMV in liver transplant recipients, but their toxicity needs to be balanced against the benefits. The choice of prevention strategy (prophylaxis or preemptive treatment) depends on the donor/recipient sero-status but may vary between institutions. We conducted a series of consultations and roundtable discussions with German liver transplant center representatives. Based on 20 out of 22 centers, we herein summarize the current approaches to CMV prevention and treatment in the context of liver transplantation in Germany. In 90% of centers, transient prophylaxis with ganciclovir or valganciclovir was standard of care in high-risk (donor CMV positive, recipient CMV naive) settings, while preemptive therapy (based on CMV viremia detected during (bi) weekly PCR testing for circulating CMV-DNA) was preferred in moderate- and low-risk settings. Duration of prophylaxis or intense surveillance was 3–6 months. In the case of CMV infection, immunosuppression was adapted. In most centers, antiviral treatment was initiated based on PCR results (median threshold value of 1000 copies/mL) with or without symptoms. Therefore, German transplant centers report similar approaches to the prevention and management of CMV infection in liver transplantation.


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