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1.
Pretransplant predictors of early mortality in adult recipients of liver transplantation in the MELD-Na Era.
Pozo-Laderas, JC, Rodríguez-Perálvarez, M, Muñoz-Villanueva, MC, Rivera-Espinar, F, Durban-García, I, Muñoz-Trujillo, J, Robles-Arista, JC, Briceño-Delgado, J
Medicina intensiva. 2019;(5):261-269
Abstract
AIMS: To identify pretransplant predictors of early mortality (90 days after transplantation) and evaluate their discriminating capacity in adult liver transplant recipients (LTR). DESIGN An observational, retrospective, nested cases-controls study from a consecutive cohort of LTRs was carried out. SETTING University hospital. PATIENTS All consecutive LTR between January 2003 and December 2016 were eligible for inclusion. Patients with acute liver failure, previous graft dysfunction, simultaneous multiple organ transplantation, non-heart beating donors, and those needing urgent retransplantation during the study period were excluded. The analysis comprised 471 patients. MAIN VARIABLES OF INTEREST Pretransplant characteristics were the main variables of interest. The LTR were grouped according to the dependent variable (early mortality). Multivariate logistic regression analysis was conducted to identify predictors of early mortality. The discriminating capacity of the models obtained was evaluated by comparing ROC curves (models versus MELD-Na). RESULTS The MELD-Na score (OR = 1.069, 95% CI = 1.014-1.127), age > 60 years (OR = 2.479, 95% CI = 1.226-5.015), and LTR height < 163cm (OR = 4.092, 95% CI = 2.115-7.917) were identified as independent predictors of early mortality. The cause of transplantation (hepatocellular carcinoma or decompensated cirrhosis) was identified as a confounding factor. CONCLUSIONS In LTR due to decompensated cirrhosis, the MELD-Na score, age > 60 years, and height < 163cm are independent predictors of early mortality. These factors provide a better classification model than the MELD-Na score for early post-transplant mortality.
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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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Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation.
Iavarone, M, Invernizzi, F, Czauderna, C, Sanduzzi-Zamparelli, M, Bhoori, S, Amaddeo, G, Manini, MA, López, MF, Anders, M, Pinter, M, et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019;(11):3176-3184
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Abstract
Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7-19.1) and 38.4 months (95% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.
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It takes a village: primary care of the pediatric liver transplant recipient.
Hassan, S, Ng, VL, Aqul, A
Current opinion in pediatrics. 2019;(5):636-644
Abstract
PURPOSE OF REVIEW Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. RECENT FINDINGS Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. SUMMARY Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.
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Liver Transplantation for Homozygous Familial Hypercholesterolemia.
Ishigaki, Y, Kawagishi, N, Hasegawa, Y, Sawada, S, Katagiri, H, Satomi, S, Oikawa, S
Journal of atherosclerosis and thrombosis. 2019;(2):121-127
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Abstract
Pharmacological treatments to decrease low-density lipoprotein (LDL) cholesterol (LDL-C) have limited effects on patients with homozygous familial hypercholesterolemia (HoFH). Since LDL receptors are located mainly in the liver, liver transplantation is considered to be the only way to correct the hepatic cholesterol metabolism abnormalities in HoFH. Liver transplantations, including those combined with heart transplantation, for HoFH have been increasing since 1984, making this a globally established therapeutic option for HoFH. Plasma LDL-C is reported to be dramatically lowered, by 80%, after transplantation, with the rapid regression of cutaneous and tendinous xanthomas. However, long-term cardiovascular benefits remain unclear. The major concerns about liver transplantation include surgical complications, the need for lifelong immunosuppressive therapy, and rejection. In addition, organ transplantations from deceased donors are extremely rare in Japan. We experienced two pediatric siblings with HoFH who received living-donor liver transplantations from their heterozygous parents. Their plasma LDL-C levels decreased immediately and stabilized at approximately 200 mg/dL. Both developed normally with the administration of lipid-lowering medications and have been free of severe problems for more than 10 years, to date, since transplantation. In Japan, where the shortage of deceased donors is critical, the combination of living-donor liver transplant from a heterozygous donor, that is, usually a parent, and medication is regarded as a valid therapeutic option for HoFH. Further studies and clinical experience are required to establish liver transplantation as a safe and effective treatment for HoFH.
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Perioperative Management of the Liver Transplant Recipient.
Kramer, DJ, Siegal, EM, Frogge, SJ, Chadha, MS
Critical care clinics. 2019;(1):95-105
Abstract
Perioperative management of the liver transplant recipient is a team effort that requires close collaboration between intensivist, surgeon, anesthesiologist, hepatologist, nephrologist, other specialists, and hospital staff before and after surgery. Transplant viability must be reassessed regularly and particularly with each donor organ. Regular discussions with patient and family facilitate realistic determinations of goals based on patient aspirations and clinical realities. Early attention to hemodynamics with optimal resuscitation and judicious vasopressor support, respiratory care designed to minimize iatrogenic injury, and early renal support is key. Preoperative and postoperative nutritional support and physical rehabilitation should remain a focus.
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Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.
Charles, FG, Murray, LJ, Giordano, C, Spiess, BD
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2019;(12):1501-1513
Abstract
PURPOSE Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.
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Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation.
Silva, JT, San-Juan, R, Fernández-Ruiz, M, Aguado, JM
World journal of gastroenterology. 2019;(26):3291-3298
Abstract
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.
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Deep vein thrombosis during long-term surveillance of patients with liver transplantation.
Balaceanu, A
Irish journal of medical science. 2019;(4):1191-1193
Abstract
BACKGROUND In the European Liver Transplant Registry, there are 137,863 liver transplantations recorded. Forty-one percent of patients survived 20 years after liver transplantation in the European countries. From 1988, when the US database for liver transplantation was created, to 2006, there are more than 56,000 liver transplants. Almost 80% of the liver transplant recipients survived 5 years after transplantation. The incidence of deep vein thrombosis (DVT) in the European population is 70-140/100.000 person-years. Cancer, paresis, immobilization, thrombophilia, inflammatory bowel disease, replacement hormonal or contraceptive therapies are associated with an increased risk of occurrence DVT or complications. The incidence of DVT in long-term surveillance of liver transplant recipients is unknown. Immunosuppressive therapy, thrombophilia abnormalities, hepatitis C and hepatocellular carcinoma recurrence, renal insufficiency, malignant tumours, obesity and diabetes were associated with DVT in long-term post-liver transplantation. The reported maximum time between liver transplantation and DVT was 210 days. AIM: The aim of the study is to update existing data in the literature regarding the occurrence and management of deep vein thrombosis in liver transplant patients over the long-term surveillence period. CONCLUSIONS There are no specific guideline recommendations regarding acute DVT treatment in long-term surveillance after liver transplantation. Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and vitamin K antagonist (VKA) are the anticoagulants used in specific complications post-transplantation. The safety and the efficacy of direct anticoagulants in liver transplantation recipients need to be assessed in future trials. Given that long-term survival of liver transplantation is much improved, complications associated with transplantation and ageing require appropriate cardiovascular guidelines.
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NAFLD and Liver Transplantation in Children-Working Group Report From the ILTS Single Topic Conference on NAFLD.
Cananzi, M, Vajro, P, Rela, M, Dhawan, A
Transplantation. 2019;(1):68-70
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has now become a common cause of chronic liver disease in children; however, unlike adults liver transplantation is rarely required as treatment. It is important that in children presenting with NAFLD, secondary causes of fatty liver particularly inherited metabolic defects should be excluded. METHODS A pediatric working group comprised of 3 hepatologists and a liver transplant surgeon was tasked with a set of questions to address the current state of evidence and knowledge about NAFLD in children with particular focus on liver transplantation. A systematic review of the English literature regarding pediatric NAFLD (from birth to 18 years of age) published in the last 2 decades (2000-2018) was carried out. The evidence was evaluated by the subgroup members and further discussed with the wider workshop faculty leading to the recommendations for best practice. RESULTS Given the paucity of literature on the subject good quality of evidence was only available on risk factors for NAFLD and medical treatment where the group could make recommendation with high/moderate strength. The evidence on natural history and indications for liver transplantation was poor hence group could not make any recommendations. CONCLUSIONS Based on the existing literature and subgroups, collective experience NAFLD unlike in adults is a very rare indication for liver transplantation in children. No definitive recommendations could be made about the natural history, indications, and outcome of liver transplantation for NAFLD in children.