Status Of Liver Transplant Recipients Research Articles

Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

From Listing to Recovery: A Review of Nutritional Status Assessment and Management in Liver Transplant Patients.

Liver transplantation (LT) is a complex surgical procedure requiring thorough pre- and post-operative planning and care. The nutritional status of the patient before, during, and after LT is crucial to surgical success and long-term prognosis. This review aims to assess nutritional status assessment and management before, during, and after LT, with a focus on patients who have undergone bariatric surgery. We performed a comprehensive topic search on MEDLINE, Ovid, In-Process, Cochrane Library, EMBASE, and PubMed up to March 2023. It identifies key factors influencing the nutritional status of liver transplant patients, such as pre-existing malnutrition, the type and severity of liver disease, comorbidities, and immunosuppressive medications. The review highlights the importance of pre-operative nutritional assessment and intervention, close nutritional status monitoring, individualised nutrition care plans, and ongoing nutritional support and monitoring after LT. The review concludes by examining the effect of bariatric surgery on the nutritional status of liver transplant recipients. The review offers valuable insights into the challenges and opportunities for optimising nutritional status before, during, and after LT.

Perioperative Thromboelastometry for Adult Living Donor Liver Transplant Recipients with a Tendency to Hypercoagulability: A Prospective Observational Cohort Study

Background: Hypercoagulability can lead to serious thromboembolic events. The aim of this study was to assess the perioperative coagulation status in liver transplant recipients with a tendency to hypercoagulability. Methods: In a prospective observational study (South African Cochrane Registry 201405000814129), 151 potential liver transplant recipients were screened for thrombophilic factors from October 2014 to June 2017, and 57 potential recipients fulfilled the inclusion criterion of presenting two or more of the following thrombophilic factors: low protein C, low protein S, low anti-thrombin, increased homocystein, increased antiphospholipid IgG/IgM antibodies, increased lupus anticoagulant, and positive Factor V Leiden mutation. Seven patients were excluded from the study because they fulfilled the exclusion criteria of cancelling the liver transplantation, oral anticoagulation, or intraoperative treatment with rFVIIa. Accordingly, 50 patients were included in the final analysis. Thromboelastometry (ROTEM) (EXTEM, INTEM and FIBTEM) and conventional coagulation tests (CCT) were performed preoperatively, during the anhepatic phase, post reperfusion, and on postoperative days (POD) 1, 3 and 7. ROTEM was used to guide blood product transfusion. Heparin was infused (60-180 U/kg/day) postoperatively for 3 days and then was replaced by low-molecular-weight heparin (20 mg/12 h). Results: FIBTEM MCF significantly increased postoperatively above reference range on POD 7 despite normal fibrinogen plasma concentrations (p < 0.05). Both EXTEM and INTEM demonstrated significant changes with the phases of transplantation (p < 0.05), but with no intra- or postoperative hypercoagulability observed. INTEM CT (reference range, 100-240 s) normalized on POD 3 and 7 (196.1 ± 69.0 and 182.7 ± 63.8 s, respectively), despite prolonged aPTT (59.7 ± 18.7 and 46.4 ± 15.7 s, respectively; reference range, 20-40 s). Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) were reported in 12.0% and 2.0%, respectively, mainly after critical care discharge and with high FIBTEM MCF values in 57% on POD 3 and 86% on POD 7. Receiver operating characteristics curve analyses of FIBTEM MCF were significant predictors for thromboembolic events with optimum cut-off, area under the curve and standard error on POD 3 (>23 mm, 0.779 and 0.097; p = 0.004) and POD 7 (>28 mm, 0.706 and 0.089; p = 0.020). Red blood cells (mean ± SD, 8.68 ± 5.81 units) were transfused in 76%, fresh frozen plasma (8.26 ± 4.14 units) in 62%, and cryoprecipitate (12.0 ± 3.68 units) in 28% of recipients. None of the recipients received intraoperative platelet transfusion or any postoperative transfusion. Main transplant indication was hepatitis C infection in 82%. 76% of recipients included in this highly selected patient population showed increased lupus anticoagulant, 2% increased antiphospholipid IgG/IgM antibodies, 20% increased homocysteine, 74% decreased anti-thrombin, 78% decreased protein C, 34% decreased protein S, and 24% a positive Factor V Leiden mutation. Overall 1-year survival was 62%. Conclusion: A significant postoperative step-wise increase in FIBTEM MCF beyond the reference range was observed despite normal fibrinogen plasma concentrations, and FIBTEM MCF was a predictor for thromboembolic events in this study population, particularly after POD 3 and 7 on surgical wards when CCTs failed to detect this condition. However, the predictive value of FIBTEM MCF for postoperative HAT and PVT needs to be confirmed in a larger patient population. A ROTEM-guided anticoagulation regime needs to be developed and investigated in future studies.

Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection

Background/AimsThe relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR.MethodsWe retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers.ResultsBPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive.ConclusionThe results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.

Health-related quality of life and affective status in liver transplant recipients and patients on the waiting list with low MELD scores

BackgroundThis study seeks to examine the impact of orthotopic liver transplantation (OLT) on Health-Related Quality of Life (HRQoL) and mental health in patients with different MELD scores. MethodsPatients who has undergone orthotopic liver transplant (OLT) or were on the waiting list for OLT were submitted to HRQoL and depression/anxiety assessment by questionnaire: Short-Form 36 (SF-36), Questions on Life Satisfaction (FLZ-M), Patient Health Questionnaire-4 (PHQ-4). Data were analysed following division of patients into three groups: pretransplant patients with a MELD score <10, ≥10, and OLT recipients. ResultsThe surveys were sent to 940 consecutive patients within one week in June 2013. Of these 940 patients, 869 (92.4%) met the inclusion criteria. In total, 291 (33.5%) eligible questionnaires (OLT group: 235, MELD <10: 25; MELD _10: 31) were suitable for analysis. General health (GH), vitality (VIT), and mental health (MH) were lower in both pretransplant groups compared to the OLT group (all p < 0.05). Anxiety and depression were higher in the MELD <10 group than in the OLT group (anxiety: p < 0.05; depression: p < 0.01). DiscussionPatients with low MELD scores seem to benefit from OLT with regards to HRQoL and mental health.

Hemostatic status in liver transplantation: association between preoperative procoagulants/anticoagulants and postoperative hemorrhaging/thrombosis.

The delicate rebalanced hemostatic status of liver transplant recipients may lead to both hemorrhagic and thrombotic tendencies in this population. The aim of this study was to investigate the association between pretransplant procoagulants/anticoagulants and posttransplant bleeding and thrombosis among living donor liver transplant recipients. The study subjects were 403 consecutive recipients with chronic liver disease. Perioperative variables, including preoperative values for procoagulants and anticoagulants, were assessed to determine their association with posttransplant hemorrhaging and thrombosis. There were 35 hemorrhagic complications (9%) and 21 thrombotic complications (5%). In logistic regression analyses, a higher Model for End-Stage Liver Disease score (P = 0.01) and a lower fibrinogen value (P < 0.001) were independently associated with hemorrhaging, whereas only a lower protein C value (P < 0.001) was independently associated with thrombosis. In a receiver operating characteristic analysis, a low preoperative protein C value (with the most accurate cutoff value being 25%) was a reliable predictor of thrombotic complications after liver transplantation (area under the curve = 0.921, P < 0.001, sensitivity = 0.9, specificity = 0.8). In conclusion, the decreases in both procoagulants and anticoagulants in liver transplant recipients may additively result in a delicate hemostatic balance and predispose patients to both hemorrhagic and thrombotic complications. A lower preoperative protein C value (<25%) was demonstrated to be a significant and reliable predictor of postoperative thrombotic complications in liver transplant recipients.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. &nbsp;Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time.Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation.Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals.Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1.Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

The effect of self‐efficacy, depression and symptom distress on employment status and leisure activities of liver transplant recipients

To examine the effect of self-efficacy, subjective work ability, depression and symptom distress on and to provide a description of, the employment and leisure activities of liver transplant recipients. Return to work and leisure activities have become an important aspect of life for liver transplant recipients worldwide. An investigation of the factors that influence the employment status and leisure activities has been recommended as a means to help transplant recipients restore their productivity. This was a cross-sectional, descriptive and correlational study in 2010. A convenience sampling method was used. Data were collected using a set of questionnaires that were administered retrospectively. A total of 106 liver transplant patients were included in this study. The post-transplantation employment rate was 45.2%. The positive predictors of employment were higher subjective work ability and higher symptom distress. Gender (female), monthly family income (<US $2,000), depression and unemployment pre-transplantation were negatively associated with employment status. Of the 106 patients, 62 (58.5%) were in the low-diversity group (score of less than 3) of leisure activities. Monthly family income of <US $2,000 was associated with a low diversity of participation in leisure activities. Subjective work ability and symptom distress were positive predictors of employment, while depression was a negative predictor. Nurses in the transplant team should focus on increasing a sense of confidence, decreasing depressive symptoms and monitoring the severity of symptoms to improve the employment status of liver transplant recipients.

Affective Status in Liver Transplant Recipients as a Function of Self-perception of General Health

ObjectiveWe aimed to determine whether there were differences with regard to anxiety and depressive symptomatology between liver transplant recipients with better (G1) versus worse (G2) self-perceptions of general health compared with pre–liver transplantation cirrhotic patients (G3). MethodsThe groups of patients included 168 recipients including 85 and 83 with better or worse self-perceptions of general health, respectively, and 75 cirrhotic pre–liver transplantation patients. For the psychological assessment we used the Hospital Anxiety and Depression Scale and the general health dimension of the SF-36 Health Questionnaire. The following analyses were used: Analysis of variance (ANOVA) with post hoc pairwise comparisons by means of Tukey's test and Cohen's d, an effect size index. ResultsSignificant differences were observed among the three groups for the variables of anxiety (P = .000) and depression (P = .000). Specifically, liver transplant recipients with better self-perceptions of general health displayed lower scores (better mental health) compared with those showing worse self-perceptions or cirrhotic patients. There were no differences between the latter two groups. The differences in these variables were relevant (large effect sizes) for anxiety (Cohen's d1–2 = −1.075, Cohen's d1–3 = −1.155) and for depression (Cohen's d1–2 = −1.145, Cohen's d1–3 = −1.158). ConclusionThe anxious-depressive status was not necessarily better among liver transplant recipients. There was great variability among them as a function of self-perceived general health. Transplant recipients with worse self-perception of general health presented the same anxiety-depressive levels as patients with severe liver disease in the pretransplantation phase; the latter groups reach the clinical threshold on the depression scale.

Alterations of immune status in liver transplant patients with sepsis

To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents. A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis: A. sepsis after transplantation (TS, n = 11), B. severe sepsis after transplantation (TSS, n = 10), C. sepsis without transplantation (NTS, n = 15) and D. severe sepsis without transplantation (NTSS, n = 11). Ten healthy volunteers were selected as the control group. Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte. The APACHII and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01). In addition, SOFA score in TSS group was significantly higher than that in NTSS group (17.0 ± 4.5 vs 12.1 ± 2.8, P < 0.01). The percentages of T cell in 4 groups were all significantly lower than healthy volunteers (all P < 0.01). The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups (P = 0.095). As compared with the control group, the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 ± 0.012, 0.047 ± 0.018 vs 0.062 ± 0.006) while the level of IL-10 was higher ((32.6 ± 7.5), (25.9 ± 4.3) vs (8.2 ± 1.4) ng/L, all P < 0.05). And the difference was more significant in the TSS group. As compared with the healther, the percentage of CD4(+)CD25(+)Foxp3(+)Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%, P < 0.01), and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ± 0.52%, P = 0.003). No significant difference existed in the percentage of Treg between the TS and control groups (P = 0.398). And it was significantly higher that in the TSS group (5.16% ± 0.99% vs 4.06% ± 0.52%, P = 0.006). But the magnitude of increase level was not so great as that in the NTSS group. The changes of Foxp3 mRNA demonstrated the similar trend as the percentage of Treg. The immune states of transplant recipients with sepsis are comparable with healthy persons during sepsis. It may subsequently develop into serious immunosuppression. Immunosuppressant should be withdrawn in severe sepsis stage so as to reconstitute the immune system.

Factors Influencing Posttransplantation Employment: Does Depression Have an Impact?

Background Depressive disorders are the leading cause of disability in the United States. Liver transplant recipients often have significant psychiatric morbidity, including depression. One of the potential consequences of depression is the inability to work. Objective The objective of this study was to determine if there is any relationship between depression and posttransplantation employment status in liver transplant recipients. Methods Patients, 18 years of age or older, who had received liver transplants from January 2007 to July 2009 were identified for the retrospective analysis. Individual posttransplantation patient charts were reviewed for patient demographics, transplantation indication, employment history, depression diagnosis, and medications. The pretransplantation charts were used to obtain family psychiatric history, patient psychiatric history, past drug, alcohol, and tobacco use, and pretransplantation employment status. Results A total of 91 patients were evaluated, of which 59.3% were males and 40.7% were females, with a mean age of 56 years. In our sample, 23% and 29% of patients were depressed pretransplantation and posttransplantation, respectively. The number of unemployed patients also increased from 10.9%–23.1%. A logistic regression was performed to identify the factors influencing employment posttransplantation, which indicated pretransplantation employment, gender (males more likely to return to work), and depression post transplantation as significant factors with odds rations of 128, 4.1, and 11.5 and corresponding P values of <.0001, .04 and .008, respectively. Conclusion Posttransplantation depression is significantly associated with post–liver transplantation unemployment. Improved management of depression may facilitate a patient's return to work after transplantation.

Nutritional Status in Liver Transplant Recipients

Assessing the nutritional status of patients with liver disease can be difficult because of the pathological changes that occur with the disease state. Malnutrition is common in patients with end-stage liver disease, making the ability to detect alterations in nutritional status vital for the clinician. Anthropometry, laboratory values, body composition analysis, subjective global assessment, and handgrip strength are tools that the clinician can use to help determine a patient's nutritional status. Early detection and interventions to correct nutritional deficits in patients with liver disease may help improve their morbidity and mortality.

The impact of MELD allocation on simultaneous liver-kidney transplantation

Model for End-Stage Liver Disease (MELD) allocation has improved the process for ranking patients on the liver transplant list. One unintended consequence has been an increase in the number of simultaneous liver-kidney (SLK) transplants. Some have argued that the system unfairly advantages patients with kidney disease and that some kidneys are being prematurely placed in SLK transplantation. This review summarizes the MELD score, assessment of kidney function in cirrhosis, the impact of kidney function in liver disease, and changes in kidney function status in liver transplant recipients in the MELD era. Finally, recommendations regarding who should receive SLK transplants are reviewed.

Cardiac morbidity and mortality related to orthotopic liver transplantation

This article briefly discusses the cardiac status of liver transplant recipients and their preoperative cardiac evaluation. It describes in detail perioperative and early and late postoperative complications as well as the cardiac problems associated with immunosuppression. The preoperative cardiovascular status of patients is important in determining how they cope with the stresses imposed by liver transplantation. Minor early cardiac events are common and may influence longer term cardiac morbidity. Immunosuppressive therapy may have short term effects but is likely to adversely affect long term cardiac risk.

Quality of life, employment, and alcohol consumption after liver transplantation

This article reviews the main results and describes the most prevalent design characteristics of the 89 studies included in our comprehensive meta-analysis of quality of life, employment, and alcohol consumption after liver transplantation. In general, the health-related quality of life of recipients was impaired before and improved after transplantation. Recipients reported large gains in those aspects of quality of life most affected by physical health and smaller improvements in areas affected by psychologic functioning. No utility-based measures have been used with liver transplant recipients, so the necessary quality-of-life weights for use in cost-effectiveness evaluations of liver transplantation are lacking. Before transplantation, the percentage of candidates with alcoholic liver disease who worked was lower than that of candidates with nonalcoholic liver disease; after transplantation, however, there was no difference in the rates of employment. None of the included articles described the types of wages and benefits associated with jobs before or after transplantation or the extent to which health insurance benefits associated with employment motivated changes in work status. No difference was found in the proportion of recipients with alcoholic and nonalcoholic liver disease that reported using alcohol after transplantation. Posttransplantation abstinence from alcohol use was greater among those patients who had been abstinent for longer than 6 months before transplantation. No difference was found between the rates of posttransplantation employment of alcohol users and nonusers; however, few studies directly evaluated this question. Because the studies in this meta-analysis used nonvalidated heterogeneous instruments to measure quality of life, employment, and alcohol consumption, the ability to combine results among studies and to compare the outcomes for liver transplant recipients with other patient populations was limited. Additional heterogeneity in the selection of control groups prevented comparisons of results among groups of transplant recipients. Because of these design limitations, clinically important questions regarding the quality of life and functional status of liver transplant recipients remain unanswered.

Assessment of immunologic status of liver transplant recipients by peripheral blood mononuclear cells in response to stimulation by donor alloantigen.

To determine whether there is a role for assessing peripheral blood mononuclear cell (PBMC) cytokine patterns as a means of measuring the immunologic and clinical status of liver transplant recipients. The role of assessing cytokine patterns in the prediction of clinical graft rejection or acceptance remains unclear. The purpose of this study was to examine the cytokine profiles of PBMC stimulated in vitro with donor alloantigen and to correlate prospectively the data with clinical assessment of graft status in orthotopic liver transplant (OLT) recipients. PBMCs from OLT recipients were examined for proliferation and cytokine mRNA expression after stimulation by donor alloantigen, third-party alloantigen, or phytohemagglutinin (PHA). mRNA extracted from PBMC was amplified by reverse transcriptase-polymerase chain reaction with oligospecific primer pairs for interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta. Results were prospectively correlated with each patient's allograft status. Increased IL-4 and TGF-beta and decreased IL-2, IFNgamma, and TNF-alpha mRNA expression by PBMCs in response to donor alloantigen stimulation predicted immunologic graft stability over a minimum 60-day interval compared with mRNA expression of PBMCs from patients with established rejection or those who experienced a rejection episode within a 30-day period (p < 0.05). Stimulation of recipient PBMCs with third-party alloantigens or PHA yielded similar but less specific results. PBMC proliferation to varying antigenic stimulation did not correlate with clinical graft status, nor did cytokine production by unstimulated PBMC. Prospective assessment of cytokine expression by PBMC from OLT recipients in response to stimulation by donor alloantigen is helpful for predicting the clinical status of the allograft and may be useful in the development of more precise immunologic monitoring protocols.

Assessment of Immune Status of Liver Transplant Recipients by Peripheral Blood Mononuclear Cells in Response to Stimulation by Donor-specific Alloantigen.

27 Objective. The role of assessing cytokine patterns in predicting clinical graft rejection or immunological graft stability (absence of rejection) remains unclear. The purpose of this study was to examine the effect of donor-specific alloantigenic stimulation of peripheral blood mononuclear cells (PBMC) from orthotopic liver transplant (OLT) recipients on cellular proliferative responses and cytokine profiles for a prospective correlation with clinical assessment of graft status. Methods. Donor alloantigens obtained at time of organ retrieval were stored at −70°C until utilized. PBMC from OLT recipients (n=45) were isolated and examined for proliferation and cytokine mRNA expression following stimulation by donor-specific alloantigen, third-party alloantigen or phytohemaglutinin (PHA). Recipient PBMC proliferation in response to stimulation was assessed by one-way mixed lymphocyte reaction. mRNA extracted from resting or stimulated recipient PBMC was amplified by reverse transcriptase PCR with oligo-specific primer pairs for interleukins (IL)-2, -4, -6, -10, IFN-γ, TNF-α and TGF-β. The level of cytokine gene expression was performed by semiquantitative analysis with β-actin expression set at 1000 units/μg and negative control at 0 units/μg of cDNA. Results were correlated prospectively over a 60 day interval with the patients' clinical and histological allograft status. Results. Increased IL-4 and TGF-β and decreased IL-2, IFN-γ and TNF-α mRNA expression by PBMC in response to donor-specific alloantigen stimulation predicted immunological graft stability (absence of rejection, n=30) over a minimum 60 day interval (p<0.05 compared to mRNA expression of PBMC from patients with unsuspected rejection or those who experienced a rejection episode within a 30 day period from the time of the cytokine analysis, n=15). Stimulation of recipient PBMC with third-party alloantigens or PHA yielded similar but less specific results. Recipient PBMC proliferation to the varying antigenic stimulation did not correlate with clinical graft status, nor did cytokine production by unstimulated PBMC from the OLT recipients. Conclusions. Prospective assessment of cytokine expression by PBMC from OLT recipients in response to stimulation by donor alloantigen is helpful for predicting the clinical status of the allograft and may be useful in the development of more precise immunological monitoring protocols.