Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Fine-mapping butyrophilin family genes revealed several polymorphisms influencing viral genotype selection in hepatitis C infection.

Host-viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Protoneutron star cooling with convection: the effect of the symmetry energy.

We model neutrino emission from a newly born neutron star subsequent to a supernova explosion to study its sensitivity to the equation of state, neutrino opacities, and convective instabilities at high baryon density. We find the time period and spatial extent over which convection operates is sensitive to the behavior of the nuclear symmetry energy at and above nuclear density. When convection ends within the protoneutron star, there is a break in the predicted neutrino emission that may be clearly observable.

Attitude towards related living donation among candidates on the liver transplant waiting list.

OBJECTIVE: To analyze attitude of patients on the liver transplant waiting list toward living donation (LD). DESIGN AND PATIENTS: Patients on the transplant waiting list -2003-2005 (n = 164)- were selected. Attitude was evaluated using a validated questionnaire, completed by an independent healthcare professional. RESULTS: The questionnaire completion rate was 97% (n = 159). A total of 87% (n = 138) of patients stated that they would donate an organ while alive if a family member needed one. However, only 39% (n = 61) would be prepared to receive a liver donation from a living relative and 50% would prefer to wait on the list (n = 80). 90% accepted that living liver donation involves a certain amount of risk. This assumption was not associated with a willingness to accept related LD (p = 0.170). A willingness to accept LD was related to patient's knowledge of his or her family's attitude toward donating an organ to the patient (p = 0.027). CONCLUSIONS: Patients had a favorable attitude toward living liv-er donation. When there was a family base that is in favor of LD then this encouraged acceptance, and therefore, it is essential to carry out family screening of patients to detect those cases in which this type of LD can be successfully requested.

Impact of Hepatic Artery Thrombosis on the Success of a Liver Transplant Because of Hepatocellular Carcinoma.

BACKGROUND: Hepatic artery thrombosis is one of the most serious complications after liver transplant. Our objective is to evaluate the impact of arterial thrombosis on the postoperative evolution of a series of patients who received transplants because of hepatocellular carcinoma. METHODS: A retrospective study of 100 consecutive hepatocellular carcinoma liver transplants was performed from January 2011 to November 2017. RESULTS: Of the 100 transplant recipients, we have observed hepatic artery thrombosis in 4 of them, 3 premature and 1 delayed. All of them received retransplants after diagnosis by hepatic artery ultrasonography and arteriography. The descriptive analysis showed a significant relationship between the appearance of hepatic artery thrombosis with variables of postoperative severity, such as arrhythmias, atelectasis, pleural effusion, hemodialysis requirement, acute kidney failure, and respiratory failure. Although patients with hepatic artery thrombosis had a longer mean hospital stay, this was not statistically significant. There was decreased graft survival and overall survival of patients who experienced hepatic artery thrombosis. CONCLUSION: Although the incidence of hepatic artery thrombosis has been relatively low (4%), the early detection of risk factors, such as arterial anatomic anomalies that condition a complex anastomosis, should draw our attention, thus having at our disposal strict ultrasonography and arteriography surveillance protocols as well as prophylactic anticoagulation guidelines for receptors at risk.

Group Psychotherapy Could Improve Depression in Cirrhotic Patients on the Liver Transplant Waiting List.

BACKGROUND: It is well-known that there is a high incidence of depression in patients on the liver transplant (LT) waiting list. However, there have been few studies of psychological intervention on these patients. OBJECTIVES: To determine symptoms of depression in patients on the LT waiting list and the impact of group psychotherapy. METHODS: Study population: patients on the LT waiting list who received group psychotherapy (n = 15). CONTROL GROUP: patients who did not receive psychotherapy (n = 10). Measurement instrument: Beck's depression test, which was provided before psychotherapy was initiated and after it was completed (after 6 months). The control group was given the questionnaire at the same 2 points in time as the study group. The psychotherapeutic method consisted of discussing patients' feelings, which dealt with several matters related to transplantation. Different coping strategies were considered. RESULTS: More than half of those surveyed initially had depressive symptoms. When the second survey was administered to the study population, all the patients improved in their psychopathological assessment. When the survey was administered to the control group, a worse psychopathological assessment was obtained in all cases. CONCLUSIONS: Our data suggest an improvement in depressive symptoms in patients on the LT waiting list after receiving group psychotherapy.

Liver Transplantation for Fulminant Hepatic Failure Due to Heat Stroke: A Case Report.

Heat stroke is a condition caused by an excessive increase in body temperature in a relatively short period of time, and is clinically characterized by central nervous system dysfunction, including delirium, seizures, coma, and severe hyperthermia. In this context, the resulting fulminant hepatic failure makes liver transplant the best choice when there are no guarantees of better results with conservative treatment. We present our experience in this case, possible alternative choices, and the current role of liver transplantation in the resolution of fulminant liver failure due to heat stroke. CASE REPORT: We report the case of a 32-year-old man with a history of malabsorption syndrome and unconfirmed celiac disease controlled with a gluten-free diet, who, while working on a typical summer midday in southern Spain (approximately 40°C), abruptly presented with loss of consciousness, coma, and a temperature of 42°C, as well as seizures at the initial medical assessment that subsided after the administration of diazepam. On the third day, the patient presented with multiple organ dysfunction syndrome, requiring mechanical ventilation, hemodialysis, and inotropic support. He did not improve with the support of conservative treatment, therefore it was decided to perform an urgent liver transplant, after which he recovered completely. CONCLUSIONS: Liver transplantation should be a main choice of treatment for cases in which, despite intensive medical treatment, there is still clinical and analytical evidence of massive and/or irreversible hepatocellular damage.

Quality of Life and Group Psychological Intervention in Patients With Cirrhosis on Liver Transplant Waiting List.

BACKGROUND: The patients on the liver transplant (LT) waiting list usually present with deterioration in their quality of life. Previous studies on psychological intervention have shown how the quality of life can be improved. OBJECTIVE: To analyze preliminary results of the influence of group psychotherapy on the quality of life of patients on the LT waiting list. METHOD: Fifteen patients on the LT waiting list who accepted receiving group psychotherapy were selected. The development of each 1 of these sessions was carried out at fortnightly periods for 6 months (12 sessions). Those patients who received a transplant and those patients who did not attend more than 6 group psychotherapy sessions were excluded. The Nottingham Health Profile was used to assess the quality of life. It consists of 38 items belonging to 6 health dimensions: energy, pain, physical mobility, emotional reaction, sleep, and social isolation. The study population was given a questionnaire before starting group psychotherapy and after it was finished. RESULTS: Of the 15 patients selected from the study population, 3 patients were given a transplant before the psychotherapy had finished, and 5 patients were excluded for not having attended more than 50% of the sessions. Therefore, the study was completed on 7 patients (n = 7). Overall, a better assessment can be seen in the second questionnaire. CONCLUSIONS: Group psychotherapy might favorably influence the quality of life of patients on the LT waiting list; therefore, it might be interesting to carry out studies on a larger scale in order to confirm these results.

Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?

BACKGROUND: The outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is excellent if it is performed within the Milan criteria (ie, single tumor less than 5 cm or 3 tumors less than 3 cm each one and no macrovascular invasion). However, after a few studies, it has become possible to have a similar survival expanding those criteria. The aim of this study is to evaluate the survival of patients with advanced HCC who, after downstaging, did not met the Milan criteria although they were within the "up to seven" benchmark, and were transplanted at our center in the last 5 years. PATIENTS AND METHODS: This is a retrospective study of patients who underwent OLT for HCC in the last 5 years in our center exceeding Milan criteria despite remaining within the "up to seven" benchmark. An observational study of associated factors with overall survival based on patient characteristics after OLT was performed. For the statistical study, the statistical program SPSS v. 17.0 (Chicago, Illinois, United States) was used. RESULTS: We studied 95 patients who had been transplanted for HCC in this period, 11 of whom met the study requirements. There were 10 (91%) males and 1 female. The mean age of the patients was 54.73 ± 8.75 years, with an average waiting list time of 279 days. Nine patients had a Child A status, with a mean Model for End-stage Liver Disease score of 9.64 (range, 6 to 16). The most frequent etiology of cirrhosis was hepatitis C virus infection in 6 patients (50%) followed by hepatitis B virus infection and ethanolic and cryptogenic cirrhosis. Ten patients (91%) had at least one pretransplantation transarterial chemoembolization. The survival of patients after 1 year was 75%, whereas after 4 years that rate decreases to 25%. At this time, we do not have any patients with a 5-year survival rate. The longest survival rate is 55 months. CONCLUSIONS: Although the expanded indication of transplantation in HCC raises controversies, especially after downstaging, it is possible to provide acceptable survival rates for patients within the expanded criteria of "up to seven" after locoregional therapies. The performance of a liver transplant in the patient profile shown in this article should also be evaluated from the perspective of the relative lack of organs for transplantation.

Long-term Survival and Evolution of the Kidney Function for Liver Transplant Patients Who Required Postoperative Dialysis.

Patients who underwent orthotopic liver transplantation (OLT) frequently develop chronic kidney disease, with those who present postoperative acute kidney failure and require renal replacement therapy (RRT) at higher risk. The objective of the study was to assess the kidney function and long-term survival of patients who underwent OLT and required RRT during or in the immediate postoperative period. Medical records of OLT and postoperative RRT patients with over 6-month survival were reviewed between January 1, 2005, and December 31, 2015. A variance analysis was carried out for repeated measurements to compare the estimate glomerular filtration rate (eGFR) baseline with the different periods (statistical significance level P < .05). Kaplan-Meier estimator was used to estimate the survival rate. Of 539 patients, 20 (3.7%) met the selection criteria. The basal eGFR at 6 months and 1, 3, 5, and 7 years was 93.41 ± 25, 78.28 ± 33, 73.06 ± 29, 65.96 ± 19, 79.81 ± 28, and 59.06 ± 24 mL/min/1.73 m2, respectively. The comparison of the eGFR baseline within the different periods was statistically significant at 1 year and at 3 years. Four patients died, 3 of them due to sepsis and 1 due to recurrence of hepatitis C virus infection. The average survival was 28 months. The probability of surviving at 1 year was 100%, at 3 years was 84.21% (95% confidence interval: 58.65-94.62), and at 5 and 10 years was 78.6% (95% confidence interval: 52.49-91.39). In conclusion, we have found a progressive worsening of the kidney function in the long term in patients who required postoperative dialysis. However, actuarial survival of these patients was very successful.

Orthotopic Liver Transplantation With Elderly Donors (Over 80 Years of Age): A Prospective Evaluation.

BACKGROUND: Our main objective was to assess the clinical outcomes obtained in a single orthotopic liver transplant (OLT) hospital with donors ≥80 years of age compared to a control group of patients subjected to OLT during the same period of time with donors who were under 65 years of age. METHODS: A prospective analysis was carried out on all the OLTs performed using liver grafts from donors in a state of brain death and with an age of ≥80 years (study group) between April 2007 and January 2015. The results of the study group (n = 36) were compared with those of a control group of patients less than 65 years of age receiving transplants with grafts. RESULTS: A total of 51 potential donors ≥80 years were assessed, with a total of 36 liver transplants being carried out and their results were compared with a control group of 283 patients receiving transplants. The median follow-up time of the patients in the series was 36 months (range: 24-120 months). Graft survival at 1, 2, and 3 years was 77%, 72%, and 62%, respectively, among the patients in the study group and 79%, 73%, and 65% among the patients in the control group, and there were no statistically significant differences. Patient survival at 1, 2, and 3 years was 86%, 82%, and 75%, respectively, among the patients in the study group and 82%, 76%, and 72% among the patients in the control group, also without there being any statistically significant differences. CONCLUSIONS: There is no age limit for liver transplant donors. The use of octogenarian donors makes it possible to increase the pool of donors while providing enough safety for the recipient.

Donors Older Than 75 Years Do Not Influence the Appearance of Biliary Complications After Liver Transplantation.

BACKGROUND: In recent years, several studies have shown that the age of the donor may be related to an increase in the occurrence of biliary complications (BCs), which remain the main cause of morbidity after liver transplantation. This study analyzed the type and management of these BCs, the impact of BCs on graft and patient survival rates, and the influence of some characteristics of donors and recipients on BC appearance in patients transplanted with donors 75 years of age or older. PATIENTS AND METHODS: From 2003 to 2016, 100 liver transplantations with donors 75 years of age or older (15.6%) were performed in our hospital. The data were compared with a control group of 400 patients with younger donors (case-control 1:4 per chronology). RESULTS: The BC rate in the group of patients transplanted with organs from elderly donors was 18%, compared to 21.5% in the control group. Specifically, in the immediate post-transplantation period, 14% of the elderly donor group and 13.8% of the control group presented some BCs, with no statistically significant differences in the incidence, type, and treatment of BCs between the two groups. The occurrence of BCs was not a factor associated with graft and patient survival rates. In the global population, donor death by cerebral vascular accident and male donors have influenced the occurrence of BCs. CONCLUSIONS: The advanced age of the donor has not influenced BC rates after transplantation.

Liver transplantation for Klatskin's tumor: contraindicated, palliative, or indicated?

OBJECTIVE: Surgical resection is the only potential curative treatment for Klatskin's tumor. In the cases of Bismuth type IV, some authors have suggested performing liver transplantation (OLT). Our aim was to present our experience in the management of Klatskin's tumor, with special reference to patients undergoing OLT. PATIENTS AND METHODS: Between May 1988 and December 2006, 66 patients were treated in our department for Klatskin's tumor, including 43 men and 23 women of overall mean age 66 years (range = 38 to 88). Twenty patients (group 1) were in operable and 46 patients underwent resection surgery (group 2), including 13 tumors considered unresectable (group 2a), with OLT contraindicated for disseminated tumor; tumor resection was possible in 23 cases (group 2b) and the remaining 10 patients who were surgically unresectable but with nondisseminated neoplasm (by staging laparotomy) underwent OLT (group 2c). The mean waiting time for OLT was 2 months (range = 1 to 4 months). RESULTS: The mean survival rates of the group 1 and 2a patients was 6 +/- 2 months and 8 +/- 2 months, respectively. Of the 23 resected patients, the 1-, 3-, and 5-year survivals were 84%, 59%, and 40%. The 1-, 3-, and 5-year survival of OLT was 80%, 60%, and 37%, respectively. Among the 10 transplanted patients, six died due to tumor recurrence at 46, 43, 19, 16, 12, and 12 months. The remaining four patients are alive and tumor-free at 120, 89, 68, and 29 months, respectively. CONCLUSIONS: A more accurate preoperative staging, perhaps by systematic use of pre-OLT laparotomy, and the use of adjuvant, and most importantly neoadjuvant therapy may improve the results of OLT in Klatskin's tumor.

Hospital personnel in surgical services in a transplant hospital faced with living liver donation: an attitudinal survey.

UNLABELLED: Living liver donation is becoming a more widely accepted practice given the decrease in donor morbidity and mortality and the beneficial results in the recipient. Use of this technique is unusual in Spain. There are a number of workers against its use within the health care system. The objective of this study was to analyze attitudes toward and the variables that affect them concerning living liver donation among surgical services in a transplant hospital. MATERIALS AND METHODS: A random survey was stratified by surgical area and job category in a Spanish third-level hospital with an ongoing solid organ transplant program. Attitudes toward living liver donation were assessed using a questionnaire about organ donation and transplantation that evaluated various psychosocial variables. Student's t test and the chi square test were used. RESULTS: A total of 263 workers were surveyed (mean age as 40 +/- 9 years). Regarding attitudes toward living liver donation, the level of acceptance was 80% (n = 211) of respondents, whereas 10% were undecided (n = 26), and another 10% were against (n = 26), assuming that the donations were related. When we asked about unrelated living donation, the percentage in favor decreased to 10% (n = 27). No differences were found with respect to job category or type of service. The variables that are related to such an attitude are the following: (1) possibility of respondent needing an organ (P = .001); (2) favorable attitude toward living kidney donation (P < .000); and (3) a belief that medical errors exist (P = .004). An important finding was that attitudes toward living liver donation were not more favorable according to whether the respondent was in favor or against cadaveric organ donation (P = .175). CONCLUSION: There was a highly favorable attitude toward living liver donation among hospital personnel in surgical services, which is an important factor to take into account if this type of donation is to be encouraged in Spain.

Gastrointestinal complications in liver transplant recipients: MITOS study.

INTRODUCTION: Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. OBJECTIVE: The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. PATIENTS AND METHODS: This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. RESULTS: The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. CONCLUSIONS: The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

OBJECTIVE: Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. RESULTS: The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.

Pretransplant CD28 Biomarker (Levels of Expression and Quantification of Molecules per Cell) in Peripheral CD4+ T Cells Predicts Acute Rejection Episodes in Liver and Kidney Recipients.

BACKGROUND: Acute rejection (AR) remains a significant cause of graft loss. Better approaches to predict AR are being investigated. Surface CD28 protein is essential for T-cell proliferation and survival as well as cytokine production. PATIENTS AND METHODS: Pretransplant CD4+CD28+ peripheral T cells were examined in 30 liver recipients (LRs) and 31 kidney recipients (KRs) by flow cytometry. RESULTS: Pretransplant CD4+CD28+ T cells in LRs were significantly lower in rejectors than nonrejectors (P = .002). Furthermore, the total number of CD28 molecules per cell in LRs (P = .02) as well as KRs (P = .047) was significantly lower in rejectors than nonrejectors. The healthy group did not display differences when compared with patients with end-stage liver disease or renal failure; however, stratification analysis displayed higher levels of CD4+CD28+ when compared with rejected LRs (P = .04) but not KRs. CD28 levels <41.94% were able to discriminate LRs at high risk of AR (P = .003). Similarly, a total number of CD28 molecules ≤8359 (P = .031) in LRs and ≤7669 (P = .046) in KRs correlated with high risk of AR. CONCLUSION: The preliminary results presented herein exhibit a fast and noninvasive method that assists clinicians to prevent AR by monitoring CD4+CD28+ peripheral T cells.

Properties of a novel glucose-enhanced beta-glucosidase purified from Streptomyces sp. (ATCC 11238).

An inducible intracellular beta-glucosidase (EC 3.2.1.21) from Streptomyces sp. QM-B814 (ATCC 11238) has been purified and characterized. The purified polypeptide is monomeric with a relative molecular mass of 62 kDa by SDS-PAGE and 42 kDa by size-exclusion chromatography; its isoelectric point is 4.2. The difference in the molecular mass values can be attributed to the glycosylated nature of the protein. The purified enzyme has a pH optimum of 6.0-6.5. The temperature optimum for activity is 50 degrees C; at this temperature the enzyme is stable for 1 h. The enzyme hydrolyzes mainly aryl-beta-glucosides but also presents significant activity against beta-linked disaccharides and maltose. The enzyme displays an unusual kinetic behavior and biphasic Lineweaver-Burk and Eadie-Hofstee plots for p-nitrophenyl-beta-D-glucoside and cellobiose were obtained. The enzyme presents beta-glycosyltransferase activity and an exoglycosidase-type action on cellodextrins. It is inhibited by delta-gluconolactone (Ki 0.44 mM) but, remarkably, glucose in the range 25-200 mM enhances the rate of p-nitrophenyl-beta-D-glucoside hydrolysis.