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Physical Condition, Glycemia, Liver Function, and Quality of Life in Liver Transplant Recipients After a 12-Month Supervised Exercise Program.
Totti, V, Tamè, M, Burra, P, Mosconi, G, Roi, GS, Sella, G, Ermolao, A, Ferrarese, A, Sgarzi, S, Savino, G, et al
Transplantation proceedings. 2019;(9):2952-2957
Abstract
BACKGROUND AND AIMS Despite the excellent long-term outcomes in liver transplant (LT) recipients, several medical complications related to lifestyle still represent an issue. This study examined the effects of a 12-month supervised aerobic and strength training program on the aerobic capacity, muscle strength, metabolic profile, liver function, and quality of life of a cohort of LT recipients. METHODS LT recipients with stable liver function were assigned to interventional exercise (group A) or usual care (group B). Aerobic capacity, muscle strength, metabolic profile, liver and kidney function, and health-related quality of life were assessed at baseline and after 6 and 12 months. Group A attended supervised training sessions 3 times per week for 12 months. Group B received general recommendations about home-based exercise. RESULTS Forty patients from 6 Italian LT centers were randomized. Twenty-nine (72.5%, men-to-women ratio 23:6, mean age, 52 ± 8 years) LT recipients completed the study. Baseline characteristics were similar between groups except for body mass index and time from LT. No episode of acute rejection nor increase of transaminases occurred. Maximum workload and body mass index increased in both groups over time, but fasting glucose significantly decreased in group A (94.0 ± 15.0 mg/dL vs 90.0 ± 17.0 mg/dL; P = .037) and increased in controls (95.0 ± 24.0 mg/dL vs 102.0 ± 34.0 mg/dL, P = .04). Upper limb muscle strength increased only in supervised LT recipients. Vitality and general and mental health domains significantly improved after physical exercise. CONCLUSIONS Supervised combined training was safe and effective in increasing aerobic capacity, muscle strength, and quality of life and in improving glucose metabolism in stable LT recipients.
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Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation.
Roullet, S, Labrouche, S, Mouton, C, Quinart, A, Nouette-Gaulain, K, Laurent, C, Freyburger, G
Journal of clinical pathology. 2019;(1):58-65
Abstract
AIMS: Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses 'Global Fibrinolytic Capacity' in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests. METHODS Thirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times. RESULTS GFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and -0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). CONCLUSIONS GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis. TRIAL REGISTRATION NUMBER NCT03012633.
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Dynamics of virus-specific T cell immunity in pediatric liver transplant recipients.
Arasaratnam, RJ, Tzannou, I, Gray, T, Aguayo-Hiraldo, PI, Kuvalekar, M, Naik, S, Gaikwad, A, Liu, H, Miloh, T, Vera, JF, et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018;(9):2238-2249
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Abstract
Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.
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Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.
Mysore, KR, Ghobrial, RM, Kannanganat, S, Minze, LJ, Graviss, EA, Nguyen, DT, Perez, KK, Li, XC
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018;(2):351-363
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Abstract
Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.
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Sodium bicarbonate infusion in patients undergoing orthotopic liver transplantation: a single center randomized controlled pilot trial.
Weinberg, L, Broad, J, Pillai, P, Chen, G, Nguyen, M, Eastwood, GM, Scurrah, N, Nikfarjam, M, Story, D, McNicol, L, et al
Clinical transplantation. 2016;(5):556-65
Abstract
BACKGROUND Liver transplantation-associated acute kidney injury (AKI) carries significant morbidity and mortality. We hypothesized that sodium bicarbonate would reduce the incidence and/or severity of liver transplantation-associated AKI. METHODS In this double-blinded pilot RCT, adult patients undergoing orthotopic liver transplantation were randomized to an infusion of either 8.4% sodium bicarbonate (0.5 mEq/kg/h for the first hour; 0.15 mEq/kg/h until completion of surgery); (n = 30) or 0.9% sodium chloride (n = 30). PRIMARY OUTCOME AKI within the first 48 h post-operatively. RESULTS There were no significant differences between the two treatment groups with regard to baseline characteristics, model for end-stage liver disease and acute physiology and chronic health evaluation (APACHE) II scores, and pre-transplantation renal function. Intra-operative factors were similar for duration of surgery, blood product requirements, crystalloid and colloid volumes infused and requirements for vasoactive therapy. Eleven patients (37%) in the bicarbonate group and 10 patients (33%) in the sodium chloride group developed a post-operative AKI (p = 0.79). Bicarbonate infusion attenuated the degree of immediate post-operative metabolic acidosis; however, this effect dissipated by 48 h. There were no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS The intra-operative infusion of sodium bicarbonate did not decrease the incidence of AKI in patients following orthotopic liver transplantation.
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Prevalence of hypertension after living-donor liver transplantation: a prospective study.
Tong, MS, Chai, HT, Liu, WH, Chen, CL, Fu, M, Lin, YH, Lin, CC, Chen, SM, Hang, CL
Transplantation proceedings. 2015;(2):445-50
Abstract
BACKGROUND Hypertension is common among patients who have undergone liver transplantation and is a major contributor to cardiovascular events. Few studies have studied the risk factors associated with post-liver transplantation (LT) hypertension. This prospective study assessed the prevalence of post-LT hypertension and associated preoperative risk factors. METHODS From May 2008 to December 2009, 79 normotensive adult patients (≥ 18 years old) who underwent living-donor LT with a median follow up of 4.79 ± 0.88 years were enrolled. Patients' pre-LT demographics, clinical data, pre-LT diabetes, and immunosuppressive agents used after LT were studied for their association with post-LT hypertension. RESULTS The prevalence of post-LT hypertension was 49.4%. The independent risk factors for post-living-donor LT hypertension were pre-LT systolic blood pressure (SBP; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00-1.09; P = .039) and post-LT administration of mammalian target of rapamycin (mTOR) inhibitors (OR, 4.08; 95% CI, 1.40-11.94; P = .010). Pre-LT diabetes had a negative predictive value (OR, 0.15; 95% CI, 0.03-0.74; P = .019). Neither age, male sex, smoking, pre-LT serum cholesterol and triglyceride levels, tacrolimus, nor glucocorticoid was associated with post-LT hypertension. CONCLUSIONS The prevalence of hypertension is high after LT. Higher pre-LT SBP and post-LT mTOR inhibitor administration predispose patients to post-LT hypertension.
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A retrospective study to compare the use of tacrolimus and cyclosporine in combination with adriamycin in post-transplant liver cancer patients.
Gu, L, Jin, W, Kan, L, Wang, X, Shan, C, Fan, H
Cell biochemistry and biophysics. 2015;(2):565-70
Abstract
The aim of this study was to compare the clinical effect of tacrolimus (TAC) versus cyclosporine (CycA) in post-transplant hepatic cancer patients undergoing adriamycin hydrochloride (ADM) chemotherapy. Patients with advanced hepatic cancer who underwent liver transplant and subsequent therapy between March 2007 and March 2009 in our hospital were selected for this study. All of these patients were treated with chemotherapeutic agent adriamycin, with respect to immunosuppressant, whereas they received either TAC or CycA, and hence represented two groups, TAC and controls, respectively. The short- and long-term outcomes of two therapies, ADM + TAC and ADM + CsA, were compared. The TAC group patients showed improved remission compared to the control group (40 cases with 46.0 % versus 32 cases with 31.1 % remission, respectively). The 5-year survival in TAC group was significantly prolonged (20.7 %) compared to that of the controls (8.7 %). The short-term outcomes, such as serum levels of calcium, biomarkers of cardiac toxicity/functioning, and regulatory T lymphocytes counts (markers of immune functioning), were found to be significantly more auspicious with TAC treatment than with CycA. Our study showed that use of TAC plus ADM resulted in improved patient survival, tolerance of the graft, and remission compared to CycA combined with ADM. The serum levels of various markers in the short follow-up analysis indicated a better cardiac and immune functioning with TAC than with CycA treatment.
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Trial of complete weaning from immunosuppression for liver transplant recipients: factors predictive of tolerance.
de la Garza, RG, Sarobe, P, Merino, J, Lasarte, JJ, D'Avola, D, Belsue, V, Delgado, JA, Silva, L, Iñarrairaegui, M, Sangro, B, et al
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2013;(9):937-44
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Abstract
Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4(+) , CD8(+) , and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range = 8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P = 0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P = 0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n = 7 for an interval > 10 years and an SI < 20), 100% reached tolerance; in the second group (n = 10 for an interval > 10 years and an SI > 20 or an interval < 10 years and an SI < 20), 60% reached tolerance; and in the third group (n = 7 for an interval < 10 years and an SI > 20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables-the time from transplantation and the SI-may help to identify these patients.
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Modified body mass index and time interval between diagnosis and operation affect survival after liver transplantation for hereditary amyloidosis: a single-center analysis.
Franz, C, Hoffmann, K, Hinz, U, Singer, R, Hund, E, Gotthardt, DN, Ganten, T, Kristen, AV, Hegenbart, U, Schönland, S, et al
Clinical transplantation. 2013;:40-8
Abstract
INTRODUCTION Familial amyloid polyneuropathy (FAP) is the most common subtype of hereditary amyloidosis. The amyloid protein transthyretin deposits as rigid amyloid fibers in the extracellular matrix of various tissues including peripheral nerves, heart, and gastrointestinal tract. As the mutated amyloid protein is mainly produced in the liver, one form of treatment to halt the progression of disease is liver transplantation (LT). This study was performed to identify risk factors for decreased overall survival. METHODS Clinical data of 21 transplant patients who underwent LT for FAP between 1996 and 2011 were analyzed retrospectively. RESULTS The majority of patients had cardiac symptoms (76%), gastrointestinal symptoms (71%), or peripheral polyneuropathy (71%). A conventional operating technique was performed on 11 patients using end-to-end caval anastomoses, while the modified piggyback technique by Belghiti was performed on 10 patients. Overall survival analysis revealed a one-yr survival rate of 74.3% and three- and five-yr survival rates of 60.0% and 52.5%, respectively. Pre-operative modified body mass index (mBMI) <700 kg g/L m² and time interval between diagnosis and operation before LT resulted in significantly lower overall survival (p = 0.0137; p = 0.033). CONCLUSION The pre-operative nutritional status and time interval between diagnosis and operation before LT influence overall survival after LT for hereditary amyloidosis.
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Regression of new-onset diabetes mellitus after conversion from tacrolimus to cyclosporine in liver transplant patients: results of a pilot study.
Lorho, R, Hardwigsen, J, Dumortier, J, Pageaux, GP, Durand, F, Bizollon, T, Blanc, AS, Di Giambattista, F, Duvoux, C
Clinics and research in hepatology and gastroenterology. 2011;(6-7):482-8
Abstract
INTRODUCTION New-onset diabetes mellitus (NODM) has important implications for long-term outcome following liver transplantation. AIM: To evaluate the impact of conversion from tacrolimus to cyclosporine in liver transplant patients presenting NODM. METHOD In a 12-month pilot study, 39 liver transplant patients with NODM were converted from tacrolimus to cyclosporine. Most patients (59%) were receiving antidiabetic therapy (18% insulin, 41% oral) and all patients had received dietary advice prior to the study. RESULTS At month 12, NODM had significantly resolved (FBG<7 mmol/L without treatment) in 36% of patients (95% CI 20.8-51.0%). In the 16 patients not receiving antidiabetic drugs at baseline, mean FBG decreased from 8.1 mmol/L to 6.6 mmol/L (P=0.008) and mean HbA(1c) decreased from 6.4 to 6.0% (P=0.05). Steroids were stopped rapidly in the nine patients receiving steroids at inclusion but NODM resolution was observed in only one of these nine patients. No significant factors were identified that could have affected NODM resolution. There were three episodes of biopsy-proven acute rejection (7.7%), no graft losses and one death. Overall, cyclosporine tolerance was good with no significant change in creatinine clearance at month 12. Total cholesterol increased from 4.6 mmol/L to 5.1 mmol/L (P<0.001). CONCLUSIONS These results suggest that liver transplant patients with NODM may benefit from conversion to cyclosporine from tacrolimus through improved glucose metabolism. Confirmation in a prospective, randomized comparative study is required.