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1.
Calciphylaxis in end-stage liver and renal disease patients before and after transplant.
Couri, T, Stier, M, Mikolajczyk, A, Aronsohn, A
Clinical transplantation. 2018;(6):e13272
Abstract
Calciphylaxis is a rare vascular disorder characterized by calcification of arterioles which causes tissue inflammation and necrosis. It is associated with the metabolic disturbances seen in end-stage renal disease (ESRD) and has also been described in patients with cirrhosis with preserved kidney function. Characteristic calciphylaxis lesions are black eschars surrounded by retiform purpura, and the gold standard for diagnosis is skin biopsy. Reported 1-year mortality rates range between 45% and 80%. No treatment modality has been evaluated in a prospective randomized trial, and reports of treatment efficacy vary. Kidney transplant has been reported as a successful therapy for calciphylaxis; however, cases exist of the initial onset of calciphylaxis following kidney transplant as well as simultaneous liver-kidney (SLK) transplant. The decision to maintain a patient with end-stage renal and liver disease on the waiting list for SLK transplant following the onset of calciphylaxis must consider the high 1-year mortality associated with this condition. More research is necessary to understand how to allocate donor allografts to manage patients with calciphylaxis and ESRD and/or cirrhosis effectively.
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2.
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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3.
Non Uremic Calciphylaxis Post Liver Transplantation: A Case Report and Literature Review of an Unusual Presentation of a Rare Disease.
Prabhakar, S, Tuffaha, AM
The American journal of case reports. 2018;:118-122
Abstract
BACKGROUND Calciphylaxis results from abnormal calcification of small to medium sized vessels, resulting in painful ischemic necrosis of the surrounding tissues. It is most commonly seen in patients with end stage renal disease on dialysis, but has also been reported in patients with preserved renal function. CASE REPORT We report a case of non uremic calciphylaxis in a 65-year-old female who presented with painful skin lesions and ulcerations involving both thighs one month after receiving a liver transplantation. She was treated with sodium thiosulfate along with wound care and hyperbaric oxygen with complete resolution of the lesions, but with residual scarring. CONCLUSIONS Non uremic calciphylaxis is a rare phenomenon that is poorly understood. It should be in the differential of unexplained skin lesions even in the absence of renal insufficiency. Sodium thiosulfate plays a role in treatment, but wound care remains the main focus of treatment.
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4.
Post-transplant Outcomes of Persons Receiving a Liver Graft for Alcoholic Liver Disease.
Rogal, S, Shenai, N, Kruckenberg, K, Rosenberger, E, Dew, MA, DiMartini, A
Alcohol and alcoholism (Oxford, Oxfordshire). 2018;(2):157-165
Abstract
AIMS: Liver transplantation (LT) for alcoholic liver disease (ALD) remains controversial yet following transplantation outcomes for patients with this disease are generally similar to patients transplanted for other types of liver diseases. METHODS In this review, we cover critical literature of ALD LT including established and recent findings of medical and psychosocial outcomes for ALD patients and compare their outcomes to other liver transplant recipients where evidence exists. RESULTS Overall medical and psychosocial outcomes for ALD LT recipients compare favorably to patients transplanted for other types of liver diseases. While alcohol relapse occurs following transplant, the rates of return to heavy alcohol use, especially at amounts that are health harmful, are low at ~20%-substantially under rates of relapse for non-transplant patients with alcohol use disorders. However, ALD LT recipients are more likely to be smokers and experience causes of death different than other LT recipients with cardiovascular and malignancies being more common. Depression is one of the more common mental health disorders experienced by ALD LT recipients and is especially important to consider due to increasing evidence of its negative impact on post-transplant survival. In general, ALD LT recipients' quality of life is as good as recipients transplanted for other types of liver disease. Post-LT re-employment and social reintegration are also comparable. CONCLUSIONS Early identification may improve outcomes with the first post-transplant year being an important time for close monitoring. Additionally, efforts to identify and treat tobacco use and depression may also improve overall outcomes in this specific population. SHORT SUMMARY In this review, we cover medical and psychosocial outcomes for ALD patients and compare their outcomes to other liver transplant recipients. While alcohol relapse occurs following transplant, the rates of return to heavy alcohol use, especially at amounts that are health harmful, are low at ~20%.
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5.
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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Combined Flush With Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions in Liver Transplantation: Preliminary Results.
León Díaz, FJ, Fernández Aguilar, JL, Nicolás de Cabo, S, Pérez Reyes, M, Sánchez Pérez, B, Montiel Casado, C, Pérez Daga, JA, Aranda Narváez, JM, Suárez Muñoz, MA, Arenas González, F, et al
Transplantation proceedings. 2018;(2):539-542
Abstract
INTRODUCTION Ischemia reperfusion injury (IRI) is the main cause of early allograft dysfunction (EAD) and subsequent primary allograft failure (PAF). OBJECTIVES The purpose of this study is to compare IRI, EAD, and PAF in liver transplantation in a cohort of patients perfused with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution versus HTK alone. METHODS A randomized trial was performed to compare outcomes in liver recipients who underwent transplantation surgery in the University Regional Hospital of Malaga, Spain. Forty patients were randomized to two groups. Primary endpoints included IRI, EAD, PAF, re-intervention, acute cellular rejection, retransplantation, arterial complications, and biliary complications at postoperative day 90. RESULTS Postoperative glutamic oxaloacetic transaminase (1869.15 ± 1559.75 UI/L vs. 953.15 ± 777.27 UI/L; P = .004) and glutamic pyruvic transaminase (1333.60 ± 1115.49 U/L vs. 721.70 ± 725.02 U/L; P = .023) were significantly higher in patients perfused with HTK alone. A clear tendency was observed in recipients perfused with HTK alone to present moderate to severe IRI (7 patients in the HTK + UW solution group vs. 15 patients in the HTK-alone solution group; P = .06), EAD (0 patients in the HTK + UW solution group vs. 0 patients in the HTK-alone solution group; P = .76), and PAF (3 patients in the HTK + UW solution group vs. 8 patients in the HTK-alone solution group; P = .15). CONCLUSIONS Initial perfusion with HTK solution followed by UW solution in liver transplantation improves early liver function as compared to perfusion with HTK alone.
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N-Acetylcysteine inhalation improves pulmonary function in patients received liver transplantation.
Li, X, Wei, X, Chen, C, Zhang, Z, Liu, D, Hei, Z, Yao, W
Bioscience reports. 2018;(5)
Abstract
Postoperative pulmonary complications (PPCs) following orthotopic liver transplantation (OLT) are associated with high morbidity and mortality rates. The effect of N-acetylcysteine (NAC) inhalation on the incidence of PPCs and the outcomes of patients undergoing OLT is unknown. This prospective randomized controlled clinical trial was conducted to investigate the effect of NAC inhalation during OLT on PPCs. Sixty patients were randomly assigned to the NAC group (n = 30) or the control group (n = 30) to receive inhaled NAC or sterilized water, respectively, for 30 min before surgery and 3 h after reperfusion. The incidence of early PPCs and outcomes including survival rate were assessed. Biomarkers including tumor necrosis factor (TNF)-α, interleukin (IL)-8, Clara cell secretory protein (CC16), intercellular adhesion molecule (ICAM)-1, and superoxide dismutase (SOD) were measured in exhaled breath condensate (EBC) at T1 (before surgery) and T2 (at the end of operation) as well as in serum at T1, T2, T3 (12 h after operation), and T4 (24 h after operation). A total of 42 patients (20 in the NAC group and 22 in the control group) were enrolled in the final analysis. Atomization inhaled NAC significantly reduced the incidence of PPCs after OLT. The levels of TNF-α, IL-8, CC16, and ICAM-1 in EBC were significantly lower, and SOD activity was higher, at T2 in the NAC group; similar data were found in serum at T2, T3, and T4. In summary, perioperative NAC inhalation may reduce the incidence of PPCs and improve patient outcomes after OLT.
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8.
Old and New Treatments for Pediatric Autoimmune Hepatitis.
Nastasio, S, Sciveres, M, Matarazzo, L, Maggiore, G
Current pediatric reviews. 2018;(3):187-195
Abstract
BACKGROUND Autoimmune hepatitis is a rare inflammatory disease of the liver that most frequently affects children and young adults. It is a multifactorial disease of unknown etiology, characteristically progressive in nature, and if left untreated, may lead to cirrhosis and terminal liver failure. It has been known for several decades now that immunosuppressive treatment convincingly alters the outcome of most patients with autoimmune hepatitis and as such it should be started as soon as diagnosis is made. Primary goals of treatment are: normalization of hepatocellular function, extinction of the hepatic necroinflammatory process, and maintenance of a stable remission, thus preventing progression to cirrhosis and its complications. This article aims to review old and new treatments for this rare chronic disorder, from the oldest and most frequently used treatment consisting of the association of prednisone and azathioprine, to alternative medical treatments, liver transplant and promising medical strategies currently under investigation. RESULT AND CONCLUSION The review will focus on the efficacy and safety profile of each drug, as well as on the published clinical experience with them in pediatric patients with autoimmune hepatitis.
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9.
Expanded Criteria Donor-Related Hyperkalemia and Postreperfusion Cardiac Arrest During Liver Transplantation: A Case Report and Literature Review.
Zhang, L, Tian, M, Wei, L, Zhu, Z
Annals of transplantation. 2018;:450-456
Abstract
BACKGROUND Liver transplantation (LT) using extended criteria donor (ECD) grafts is frequently associated with a high flush fluid potassium concentration (FFK) and acute hyperkalemia after reperfusion, which puts patients at greater risk of postreperfusion cardiac arrest (PRCA). CASE REPORT Herein, we present a case with an extremely high FFK that was successfully pretreated to avoid the risk of PRCA. A 3-year-old boy with biliary atresia underwent LT from a 623-g donation after brain death liver graft with localized frostbite on the right lobe surface. The FFK was 18.8 mmol/L after flushing with 1000 mL of 5% albumin. To prevent PRCA due to acute hyperkalemia, further portal vein (PV) flush, retrograde reperfusion via the inferior vena cava, and antegrade reperfusion via the PV were adopted to remove the excessive potassium ions. Ultimately, the liver graft was reperfused when the perfused blood potassium concentration was 7.5 mmol/L without subsequent development of PRCA during the immediate reperfusion period. Nevertheless, the patient still experienced vasoplegic syndrome during the late reperfusion period. CONCLUSIONS Our case illustrates that the FFK measurement is helpful for identifying ECD-related hyperkalemia and for providing advance warning of PRCA. Future investigations are warranted to confirm the relationship between high FFK and PRCA and to observe the effectiveness of other interventions to prevent PRCA due to ECD-related hyperkalemia.
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10.
Impact of etiological treatment on prognosis.
Su, CW, Yang, YY, Lin, HC
Hepatology international. 2018;(Suppl 1):56-67
Abstract
Portal hypertension (PHT) is a frequent and severe complication of cirrhosis. PHT may lead to the development of various complications with high mortality. Liver transplantation is the gold standard as a surgical curative treatment for end-stage liver disease. Theoretically, etiological treatment focusing on the pathophysiology of the underlying disease should be the objective of the nonsurgical management of cirrhotic PHT. Chronic viral hepatitis is the major etiology of cirrhosis and PHT. In cirrhotic patients with chronic hepatitis B virus infection, antiviral therapies can suppress viral replication, ameliorate hepatic inflammation, regress fibrosis, and restore liver functional reserve. Moreover, they can delay the progression of liver cirrhosis and ameliorate the severity of PHT. In patients with hepatitis C virus-induced liver cirrhosis, interferon and ribavirin combination therapy provide a favorable long-term prognosis, including lower rates of liver-related and non-liver-related deaths, hepatic decompensation, and hepatocellular carcinoma, particularly in those who have successful eradication of the virus after therapy. In patients with PHT, direct antivirals (DAAs) for hepatitis C virus infection have good safety profiles and excellent viral suppression. Moreover, DAAs can reduce hepatic venous pressure gradient. However, these effects are stronger during the earlier stage of liver cirrhosis. Abstinence is the cornerstone of etiological treatment for alcoholic liver disease. The effects of pharmacological treatments are not satisfactory, and additional studies are mandatory.