International Journal of Organ Transplantation Medicine最新文献

Background: Liver function indices and anti-viral immune regulatory markers can both improve graft outcomes, which lead to better post-transplantation management and increase the possibility of surveillance in liver transplant recipients with chronic hepatitis B virus (HBV) infection.

Objective: To determine the association between the interferon regulatory factor 1 (IRF1) mRNA levels and liver enzymes in HBV-infected liver transplant recipients with and without experience of rejection.

Methods: A total of 46 chronic HBV-infected patients who had undergone liver transplant surgery was divided into 2 groups of recipients "with rejection" and "without rejection.". Blood samples were collected form each patient on days 1, 4, and 7 post-transplantation. A SYBER GREEN real-time PCR was used to evaluate the expression level of IRF1 in liver recipients. Liver enzyme activities were also measured in all patients.

Results: The expression of IRF1 in the patients with rejection was up-regulated at all 3 follow-up days compared with those without rejection. The serum levels of ALT and AST were more than normal levels at 3 follow-up times in both study groups. Significant differences were found in IRF1 gene expression levels and also serum ALT levels between those with and without rejection after 7 days post-transplantation.

Conclusion: The IRF1 expression and serum ALT levels were increased significantly in patient with rejection compared to those without rejection. IRF1, an inflammatory factor, may also intensify induction of inflammatory pathways in engrafted liver and promote liver inflammation and injuries leading to liver enzymes elevation in patients with graft rejection.

[This retracts the article on p. 41 in vol. 9, PMID: 29531646.].

One of the most catastrophic complications of kidney transplantation is non-traumatic delayed bleeding caused by arterial dissection and pseudoaneurysm, endangering the survival of the graft and the patient. Herein, we discuss the management of this condition in 3 cases. The patients included 2 men, 30 and 47 years old, and a 33-year-old woman, who developed a massive hemorrhage in the second week after kidney transplant. All our patients were diabetic for more than 5 years. Massive hemorrhage occurred in the second week without any trauma or precipitating factor. A combination of antibiotic therapy, surgery and interventional procedures was required and all three transplanted kidneys inevitably had to be removed. Although there were trivial signs of infection, considerable pus and infectious and necrotic tissue were drained during graft nephrectomy. A high index of suspicion is necessary for the timely diagnosis of arterial dissection and aneurysm. Aggressive treatment with arterial drug-eluting stents and surgical drainage are necessary in order to prevent potentially fatal complications.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially cure for acute myeloid leukemia (AML). Patients who undergone HSCT are at increased risk of infection due to impaired immunity.

Objective: To evaluate the rate of bacterial, viral and fungal infection and its relationship with 2-year overall survival of AML patients who had undergone HSCT.

Methods: This was a retrospective cross-sectional study of 49 patients who underwent allogenic bone marrow transplantation (BMT) from full-matched donors at BMT Center, Imam Khomeini Hospital Complex, Tehran, Iran, from 2006 to 2013. All autologous transplantations and promyelocytic leukemia (PML) transplantations were excluded.

Results: All patients, except for one, had fever for a mean of 7 days post-transplantation and received broad-spectrum antibiotic. The rate of severe sepsis was 6.1%. None of the patients developed fungal infection during admission. The rate of admission due to sepsis after discharge was 27% in the alive group (mean onset of 54 days), and 73% in the deceased group (mean onset of 52 days) (p<0.05). The most common site of infection was lung (70%). The rate of cytomegalovirus (CMV) antigenemia (positive PP65) was 20% during the 2-year period after HSCT.

Conclusion: The rate of infection was a negative prognostic factor for 2-year overall survival. The rate of CMV antigenemia is less than similar studies (51%), which could be due to full-matched donor-recipients requiring less immunosuppression.

Background: Transfusion-transmitted virus (TTV) is a single-stranded DNA virus. Renal transplant patients have a higher risk of TTV infection.

Objective: To evaluate the prevalence of TTV and its correlation with post-renal transplantation complications in a population of Iranian patients.

Methods: A cross-sectional study was performed on 120 renal transplant recipients. TTV infection in the peripheral blood samples was detected by semi-nested polymerase chain reaction (semi-nested PCR). Then, the relationship between TTV and renal post-transplant complications was examined.

Results: 34.2% renal transplant recipients were positive for TTV. There was a significant correlation between the presence of TTV and diabetes, acute transplant rejection, and urinary tract infection. We did not find any direct correlation between the presence of TTV infection and hypertension, hyperlipidemia, respiratory tract infection, and cytomegalovirus infection.

Conclusion: We found an increased rate of TTV infection in renal transplant recipients associated with post-transplantation complications. TTV may be an important risk factor for some post-renal transplantation complications.

Background: Generating hepatocytes with complete liver functions is still a challenge and developing more functional hepatocytes is needed.

Objective: To compare various differentiation factors and protocols and introducing a preferable protocol to differentiate human-induced pluripotent stem cells (hiPSCs) into hepatocyte-like cells (HLCs).

Methods: After 3 days of the endoderm differentiation of hiPSCs, the cells were incubated with 5 hepatocyte differentiation culture media, protocols (P), for 14 days-P1: hepatocyte growth factor and fibroblast growth factor-4 (FGF-4) for the first week and oncostatin-M and dexamethasone for the second week; P2: similar to P1 but FGF4 was used in both the first and second weeks; P3: similar to P1 but FGF-4 was not used; P4: similar to P1 but FGF-4 and dexamethasone were not used; and P5: similar to P1 but FGF-4 and oncostatin-M were not used. After 17 days, characterization was done by qRT-PCR, immunofluorescence and ELISA.

Results: The mRNA expression levels of hepatocyte markers (albumin, cytokeratin-18, tyrosine aminotransferase, hepatocyte nuclear factor-4α, cytochrome-P450 7A1) increased significantly (p<0.05) in the differentiated cells by 5 different protocols. Furthermore, significant protein expression and secretion of albumin were detected in the differentiated cells by 5 different protocols. In P3, the differentiated cells had the highest exhibit of hepatocyte characteristics and in P4 they had the lowest. Moreover, in P1 and P2 similar results were observed.

Conclusion: Since P3 gave us the best results among all protocols, we recommend it as an efficient protocol to differentiate the functional HLCs from hiPSCs, which can improve cell therapies.

Background: Cellular transplantation is a promising treatment strategy for neurological diseases.

Objective: To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center.

Methods: From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015-10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson's disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50-200 (median 100) mL bone marrow was aspirated from the patients' posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3-4 hours after bone marrow collection. 5-10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4-5 hours. The median number of MNCs was 4×10⁷ (range 1-450×10⁷). The median viability of the cells was 90% (range 60%-98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy.

Results: We noted clinical improvements in 9 of 12 patients with Parkinson's disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2-4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated.

Conclusion: Most patients with advanced Parkinson's disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life.

Background: Cytomegalovirus (CMV) is the most common opportunistic viral infection in kidney transplant recipients. CMV classification is usually based on its glycoprotein B (gB) genotypes, which divides the virus into 4 strains (gB1-4).

Objective: To determine the incidence of CMV genotypes in Iran and their relation to various clinical factors.

Methods: We studied 80 renal transplant recipients admitted to our transplant referral center between 2014 and 2015. All of the studied patients were monitored every 1-2 weeks for CMV infection by immunofluorescence method. There were 34 CMV-infected patients whose sera were studied with sequencing technique to identify the 4 CMV genotypes. All patients were followed up to 6 months after transplantation.

Results: gB1 was the most common genotype (35.3%); it was followed by gB3 and gB4 (each with 17.6 %), gB2, and mixed gB1,3 and gB1,2 (each with 14.7%). Age (p=0.037), time of infection after transplantation (p=0.011), and biopsy-proven rejection (p=0.012) were associated with CMV genotype. After adjusting for covariates, significant associations were found between genotype gB1 and family relationship (p=0.047) as well as HLA mismatch (p=0.014); genotype gB3 and family relationship (p=0.011); and genotype gB4 and age (p=0.019).

Conclusion: The most common CMV gB genotype in CMV-infected kidney transplant recipients in Iran was gB1. We recommend considering related therapeutic applications in the management of such patients.

Background: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450.

Objective: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation.

Methods: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers. DNA was extracted from blood samples and analyzed by TaqMan SNP genotyping assay. The CYP2C19 genotypes were classified into poor, extensive, intermediate, and ultra-rapid metabolizer phenotypes.

Results: Viral hepatitis was the most common cause of liver disease among studied patients. The frequencies of CYP2C19 alleles *1, *17, and *2 were 66.7% (160/240), 20.8% (50/240) and 12.5% (30/240), respectively. Allele CYP2C19*3 was not found in the studied population. The most prevalent genotypes were CYP2C19 *1/*1 (47.5%) and *1/*17 (24.2%). The predicted CYP2C19 phenotypes were extensive metabolizer (47.5%), heterozygote extensive metabolizer (45.9%), ultra-rapid metabolizer (5%), and poor metabolizer (1.6%). There was no significant difference between the frequencies of CYP2C19 genotypes between healthy people and patients. The distribution of CYP2C19 genotype frequencies was not significantly associated with the underlying disease conditions (p=0.472).

Conclusion: The distribution of CYP2C19 genotype frequencies in Iranian healthy people and patients with various hepatic diseases was not significantly different. This may allow the physicians to predict a tailoring dose regimens based on the individual's metabolic capacity, decrease the risk of harmful side effects of the drugs, and optimize the treatment.