International Journal of Organ Transplantation Medicine最新文献

Background: Liver transplant recipients are treated with various drugs, the metabolism of which is dependent on the cytochrome P450 polymorphic genotype.

Objective: To identify the polymorphic variety of CYP2C19 genotype in liver allograft before and after transplantation.

Methods: The study was conducted on 88 liver recipients. The CYP2C19 genotypes in donors and recipients were the same in 32 and different in 56 recipients. Extracted genomic DNA from the leukocytes and liver graft tissues were analyzed by TaqMan SNP genotyping assay. The distributions of homozygote, heterozygote, poor and ultra-rapid metabolizers' genotypes were investigated in both groups.

Results: The distributions of CYP2C19 genotypes before transplantation in the blood and liver graft were within the normal range. After transplantation, in patients with different CYP2C19 genotype in donors and recipients, the genotypes of homozygote and ultra-rapid metabolizers were significantly decreased (p=0.024); the heterozygotes and poor metabolizer genotypes were significantly increased (p=0.017).

Conclusion: The variety in CYP2C19 genotyping must be considered in patients with different genotypes in donor and recipients to predict the dosage regimens, optimize the treatment and decrease toxicity.

Direct oral anticoagulants have suggested a favorable profile compared with vitamin K antagonists. However, the lack of treatment to reverse the effect of direct oral anticoagulants has limited its use in some patients who require rapid reversal of anticoagulation, as those included in the transplant waiting list. Idarucizumab is a recently approved drug to reverse the anticoagulant effect of dabigatran. However, the clinical experience when using this drug is scarce. Herein, we present a clinical case on anticoagulation reversal with idarucizumab to perform heart and lung transplantation in a patient with Eisenmenger syndrome.

Background: Syndrome of transient bone marrow suppression may result from various extra-hematological diseases, such as immunological deregulations, and viral infectious diseases secondarily affecting the function of hematopoietic stem cells.

Objective: To evaluate the pathogenic role of herpes viruses and their contraction with IL10 cytokine gene polymorphism, which can impair hematopoiesis in patients with transient bone marrow suppression.

Methods: In a cross-sectional study 30 patients who admitted to Namazi Hospital, affiliated to Shiraz University of Medical Sciences, with transient bone marrow suppression were recruited. Diagnosis of the transient bone marrow suppression was made by expert hematologists. A control group consisting of 100 healthy unrelated individuals was also included. One EDTA-treated blood sample was collected from each studied patients and plasma was isolated. The molecular prevalence of cytomegalovirus and HHV8 evaluated was evaluated using real-time and nested PCR protocols, respectively. The SNPs of the IL10 (rs 1800896-1082G/A) cytokine gene was evaluated by PCR-RFLP method.

Results: Cytomegalovirus and HHV8 infections were found in 2 and 3 of studied patients with transient bone marrow suppression. Significant higher frequency of IL10 G allele and GG genotype were found in HHV8-infected patients comparing to uninfected ones. Higher frequencies of A allele and AG and AA genotypes of IL10 were found in cytomegalovirus-uninfected patients comparing to infected ones, respectively. The significant higher frequencies of IL10 AA and AG genotypes were found in controls compared to bone marrow suppressed patients.

Conclusion: IL10 genetic polymorphism might have determinative role in resistance to the cytomegalovirus, especially HHV8 infections, in patients with bone marrow suppression. Focus in new interaction between HHV8 infection and IL10 genetics in bone marrow suppressed patients should be completed by the analysis of the anti-herpes virus immunity in future studies.

Despite having many advantages, living donor liver transplantation has not been adopted by western countries due to risk of nearly life-threatening complications after living donor hepatectomy (LDH). Herein, we aimed at presenting the management of a 19-year-old patient who suffered life-threatening complications after right lobe LDH. A multiple detector computed tomography (MDCT) revealed a bilioma at the cut surface of the remnant liver, for which a transhepatic drainage catheter was placed. Endoscopic retrograde cholangiopancreatography (ERCP) performed to decompress biliary tract, but the biliary tract could not be cannulized due to post-precut bleeding. On the next day, extensive crepitation was detected and MDCT showed subcutaneous emphysema, pneumoperitoneum, pneumoretroperitoneum, and pneumoscrotum (ERCP-related duodenal perforation?). However, the patient showed significant deterioration of physical examination findings, fever, and infectious parameters, and therefore was taken to the operating room. Kocher maneuver revealed no apparent duodenal perforation. Then, a 2-mm bile duct was found open at the caudate lobe, through which bile leaked. Then, common bile duct exploration and T-tube placement were performed, followed by suture closure of the bile orifice at the caudate lobe. Massive air previously identified completely disappeared one week after the operation.

Background: Umbilical hernias are common in patients with end-stage liver disease undergoing liver transplantation. Management of those persisting at the time of liver transplantation is important to define.

Objective: To evaluate the long-term results of patients undergoing simultaneous primary umbilical hernia repair (UHR) at the time of liver transplantation at a single institution.

Methods: Retrospective chart review was performed on patients undergoing simultaneous UHR and liver transplantation from 2010 through 2016. 30-day morbidity and mortality outcomes and long-term hernia recurrence were investigated.

Results: 59 patients had primary UHR at the time of liver transplantation. All hernias were reducible with no overlying skin breakdown or leakage of ascites. 30-day morbidity and mortality included 5 (8%) superficial surgical site infections, 1 (2%) deep surgical site infection, and 7 (12%) organ space infections. Unrelated to the UHR, 10 (17%) patients had an unplanned return to the operating room, 16 (27%) were readmitted within 30 days of their index operation, and 1 (2%) patient died. With a mean follow-up of 21.8 months, 7 (18%) patients experienced an umbilical hernia recurrence.

Conclusion: Despite the high perioperative morbidity associated with the transplant procedure, concurrent primary UHR resulted in an acceptable long-term recurrence rate with minimal associated morbidity.

Background: According to the basic ethical principle of non-maleficence, organ procurement systems need to be accountable to donor families. As organ donation can be potentially traumatic, donor families are at risk of developing psychological damage. Appropriate measurement tools are needed to diagnose such disorders and develop appropriate treatment measures.

Objective: To examine the appropriateness of measurement tools and approaches used in previous studies for assessing donor families' psychological well-being.

Methods: A structured online search was conducted in electronic databases namely ScienceDirect, PubMed, ProQuest, Scopus, Ovid, and Web of Science. The main inclusion criterion was the use of psychological assessment tools for data collection.

Results: 10 studies were included in which different tools had been used for measuring donor families' psychological well-being in the following 5 dimensions: stress, depression, grief, general health, and positive legacy of trauma. The major pitfalls of the reviewed studies were failure to specifically assess complicated grief and differentiating it from other psychological disorders, diversity of the tools used for psychological well-being assessment, and lack of clear definitions of donor families' psychological well-being and its dimensions.

Conclusion: Donor families' psychological well-being is a complex and multidimensional concept and the existing measurement tools cannot accurately assess it. Therefore, the concept needs to be clearly explored and defined. Developing a comprehensive measurement tool or a set of scales is necessary for the early diagnosis of any impairment in donor families' psychological well-being.

Massive post-transplantation ascites is a rare but serious condition following liver transplantation. Although, many etiologies are suggested as the cause of this complication, in some cases the definitive etiology remains unknown. Drug-induced post-transplantation ascites is one of the possible etiologies. In this study we present a case of ascites caused by tacrolimus in the post-liver transplantation period. A 49-year-old man with hepatitis B virus cirrhosis underwent liver transplantation and received tacrolimus, mycophenolate and prednisolone, as the immunosuppressive regimen. Progressive ascites developed after 10 days, in spite of a normal liver function. Various studies, including liver biopsy, were performed but we could not find any etiology for this complication. The tacrolimus was switched to rapamune. Ascites was completely disappeared and up to the last follow-up visit, the patient remained asymptomatic for more than two years. We concluded that after ruling out other etiologies, tacrolimus as a rare cause of post-transplantation ascites should be taken into account. The treatment is discontinuation of the drug.

The incidence of invasive fungal infections is lower than that of bacterial infections in heart transplant recipients. However, they are always life-threatening. Clinical manifestations may range from asymptomatic colonization to disseminated infection. This complication is responsible for significant morbidity and mortality, particularly in heart transplant recipients. Herein, we present on a cardiac transplant recipient who presented with invasive pulmonary aspergillosis quickly leading to death, in spite of early diagnosis and aggressive therapy. It just took 10 hours from the diagnosis to death. In other reports, this period was at least 12 days.

Background: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce.

Objective: To assess the effect of leflunomide on BKvirus in kidney-transplanted children.

Methods: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded.

Results: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis.

Conclusion: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30-40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.

Granulomatosis with polyangitis (GPA) is characterized by necrotizing granulomatosis of the upper and lower respiratory tract and glomerulonephritis. If GPA does not respond to appropriate management, it might result in end-stage renal disease, which may remit the disease severity. The overall impression is that immunosuppression following renal transplantation would further subside the vasculitis. However, several studies have shown that systemic vasculitis recur in 25% of patients following renal transplantation. This may indicate the perplexing nature of the immune system. One of the key factors in prevention of relapse of GPA is following up of patients by careful immunosuppressive dose adjustment and regular measurement of biomarkers for vasculitis. Herein, we describe an interesting case of biopsy-proven GPA who had a complex long history of several post-transplantation relapses in different organs with anti-neutrophil cytoplasmic antibodies seroconversion. This case emphasizes that vasculitis in particular GPA can mimic various diseases depending on which vessels and organs are affected by the inflammation and is one of the reversible causes of failure of transplanted kidney. Bearing the diagnosis in mind as one of the potential differential diagnoses of failure of renal transplantation will lead to early diagnosis and treatment of recurrent GPA.