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BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.
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Transplante de Rim , Transplante de Fígado , Adulto , Humanos , Tacrolimo/efeitos adversos , Transplante de Fígado/efeitos adversos , Basiliximab , Doadores Vivos , Preparações de Ação Retardada , Imunossupressores/efeitos adversos , Rejeição de Enxerto/prevenção & controleRESUMO
BACKGROUND: In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV. METHODS: Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems. RESULTS: There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group. CONCLUSION: In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality. REGISTRATION NUMBER: CTRI/2018/11/016315 (www.ctri.nic.in).
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Prótese Vascular , Veias Hepáticas/cirurgia , Transplante de Fígado , Politetrafluoretileno , Veia Porta/transplante , Adulto , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Sepse/mortalidade , Trombose Venosa/mortalidadeRESUMO
BACKGROUND: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.
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Transplante de Rim , Transplante de Fígado , Adulto , Basiliximab , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Proteínas Recombinantes de Fusão , EsteroidesRESUMO
Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue-specific NAT (nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNA indicative of a pretransplant naïve status. The prM-Envelope gene sequence analysis of the donor and recipient viral RNA identified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor-to-recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions.
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Dengue/etiologia , Dengue/transmissão , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado/efeitos adversos , Dengue/sangue , Vírus da Dengue , Humanos , Fígado/virologia , Hepatopatias Alcoólicas/complicações , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/sangue , Trombocitopenia/etiologiaRESUMO
Traditionally, deceased donor liver grafts receive dual perfusion (DP) through the portal vein and the hepatic artery (HA) either in situ or on the back table. HA perfusion is avoided in living donor liver grafts for fear of damage to the intima and consequent risk of hepatic artery thrombosis (HAT). However, biliary vasculature is predominantly derived from the HA. We hypothesized that antegrade perfusion of the HA in addition to the portal vein on the back table could reduce the incidence of postoperative biliary complications. Consecutive adult patients undergoing living donor liver transplantations were randomized after donor hepatectomy to receive graft perfusion of histidine-tryptophan-ketoglutarate solution either via both the HA and portal vein (DP group, n = 62) or only through the portal vein (standard perfusion [SP] group, n = 62). The primary endpoint was the occurrence of biliary complications (biliary leak/stricture). Secondary endpoints included HAT and patient survival. The incidence of biliary stricture was significantly lower in the DP group (6.5% versus 19.4%; odds ratio, 0.29; 95% confidence interval, 0.09-0.95; P = 0.04). There was no significant reduction in the incidence of HAT, bile leak, or hospital stay between the 2 groups. The 3-year mortality and graft survival rates were significantly higher among patients who received DP compared with SP (P = 0.004 and P = 0.003, respectively). On multivariate analysis, nonperfusion of the HA and preceding bile leak were found to be risk factors for the development of biliary stricture (P = 0.04 and P < 0.001, respectively). In conclusion, DP of living donor liver grafts through both the HA and portal vein on the back table may protect against the development of biliary stricture. This could translate to improved patient survival in the short term.
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Colestase/epidemiologia , Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Perfusão/métodos , Complicações Pós-Operatórias/epidemiologia , Trombose/epidemiologia , Adulto , Aloenxertos/irrigação sanguínea , Sistema Biliar/irrigação sanguínea , Sistema Biliar/patologia , Colestase/etiologia , Colestase/prevenção & controle , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/prevenção & controle , Doença Hepática Terminal/mortalidade , Feminino , Sobrevivência de Enxerto , Hepatectomia/métodos , Artéria Hepática/transplante , Humanos , Fígado/irrigação sanguínea , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Perfusão/efeitos adversos , Veia Porta/transplante , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Taxa de Sobrevida , Trombose/etiologia , Coleta de Tecidos e ÓrgãosRESUMO
The role of prostaglandin E1 (PGE1) infusion in improving early graft function has not been well defined, especially in the scenario of living donor liver transplantation (LDLT). We designed a randomized, double-blind, placebo-controlled trial to evaluate the role of perioperative PGE1 infusion in LDLT. Patients in the study arm received PGE1 (alprostadil) at the rate of 0.25 µg/kg/hour, starting at 1 hour after portal venous reperfusion, and continued for 96 hours. The primary endpoint was early allograft dysfunction (EAD). We analyzed multiple secondary endpoints including postoperative liver function and renal function parameters, acute kidney injury (AKI), hepatic artery thrombosis (HAT), postoperative bleeding, overall mortality, and posttransplant hospital stay. The incidence of EAD was lower in the PGE1 arm, although the difference did not reach statistical significance (22.4% versus 36%; P = 0.21). Among the secondary endpoints, the incidence of AKI was significantly lower in the PGE1 arm (8.2% versus 28%; P = 0.02), as were the peak and mean postoperative creatinine levels. The need for renal replacement therapy was similar between the 2 groups. Among the postoperative graft function parameters, postoperative alanine aminotransferase level was significantly lower in the PGE1 arm (P = 0.04), whereas the remaining parameters including serum bilirubin, aspartate aminotransferase, and international normalized ratio were similar between the 2 arms. There was no difference in the incidence of HAT and postoperative bleeding, in-hospital mortality, and posttransplant hospital stay between the 2 arms. Perioperative PGE1 infusion reduces the incidence of posttransplant renal dysfunction in patients undergoing LDLT. Liver Transplantation 22 1067-1074 2016 AASLD.
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Aloenxertos/efeitos dos fármacos , Alprostadil/uso terapêutico , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Substâncias Protetoras/uso terapêutico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Alprostadil/administração & dosagem , Creatinina/sangue , Método Duplo-Cego , Doença Hepática Terminal/mortalidade , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Artéria Hepática/patologia , Mortalidade Hospitalar , Humanos , Incidência , Testes de Função Renal , Tempo de Internação , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Substâncias Protetoras/administração & dosagem , Índice de Gravidade de Doença , Trombose/epidemiologia , Trombose/etiologiaRESUMO
Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late '90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.
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Ácido Quenodesoxicólico , Ácido Quenodesoxicólico/análogos & derivados , Receptores Citoplasmáticos e Nucleares , Humanos , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Ácido Quenodesoxicólico/farmacologia , Ácido Quenodesoxicólico/uso terapêutico , Animais , Ácidos e Sais Biliares/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacosRESUMO
Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.
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INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.
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Artéria Hepática , Transplante de Fígado , Complicações Pós-Operatórias , Sistema de Registros , Trombose , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Criança , Incidência , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Trombose/etiologia , Trombose/epidemiologia , Adolescente , Pré-Escolar , Feminino , Masculino , Constrição Patológica/etiologia , Lactente , Estudos Multicêntricos como AssuntoRESUMO
A young male presented with intermittent high-grade fever, asymmetric polyarthritis and erythematous, tender nodules over left shin for 2 months duration. He had a history of alcohol dependence with multiple episodes of acute pancreatitis. With polyarthritis progressing relentlessly, unresponsive to non-steroidal anti-inflammatory drugs and steroids, a provisional diagnosis of sarcoidosis was considered. Indeed, he was treated with azathioprine and rituximab with no effect. Biopsy of the skin nodule revealed subcutaneous fat necrosis, foam cells, deposition of eosinophilic amorphous material and calcification. Synovial fluid aspiration from the arthritic knee obtained purulent but surprisingly culture-negative material, rich in triglycerides. Abdominal CT confirmed chronic pancreatitis. Final diagnosis of pancreatitis, panniculitis and polyarthritis (PPP) syndrome was made. He underwent surgical pancreatic ductal drainage leading to complete remission of symptoms. PPP syndrome triad occurs due to leakage of pancreatic enzymes into systemic circulation and subsequent fat necrosis. Surgical drainage of pancreatic duct is often curative.
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Artrite , Necrose Gordurosa , Pancreatite , Paniculite , Humanos , Masculino , Pancreatite/complicações , Pancreatite/diagnóstico , Doença Aguda , Paniculite/diagnóstico , Paniculite/etiologia , Paniculite/tratamento farmacológico , Artrite/diagnóstico , Artrite/etiologia , Artrite/tratamento farmacológico , Gordura Subcutânea/patologia , Necrose Gordurosa/complicações , Necrose Gordurosa/diagnósticoRESUMO
Gastrointestinal mucormycosis (GIM) is an uncommonly encountered fungal infection following solid-organ transplantation. GIM is known to be associated with immunocompromised states, remains difficult to diagnose and often results in fatal outcomes. It is plausibly the delay in initiation of appropriate treatment strategies that leads to failure of response and patient demise. We report two cases of GIM following live donor liver transplantation, presenting with bleeding and perforation, respectively, highlighting the challenges in making a timely diagnosis of mucormycosis, particularly in immunocompromised patients.
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Transplante de Fígado , Mucormicose , Humanos , Transplante de Fígado/efeitos adversos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologia , Doadores Vivos , Cognição , Evolução FatalRESUMO
ABO incompatible liver transplants (ABOi LT) are considered as a life-saving option when compatible donor grafts are unavailable. Fourteen adults (right lobe graft) and three children (left lateral segment/lobe) who underwent ABOi LT from living donors between 2011 and 20 period were analysed for transfusions and desensitisation protocols. All recipients received packed red blood cells (PRBC) of their own group. AB plasma that does not contain any antibody was transfused in eight patients and donor group plasma in others. None of the patients developed transfusion related complications. Plasmapheresis and rituximab/bortezumab desensitisation was practised in 11 patients, only rituximab in four, only plasmapheresis in one, and no treatment in a 1 year child. Rejection was manifest in three patients while nine patients developed infections and sepsis. A working knowledge of the blood and product transfusions in ABOi LT is crucial for the anaesthesiologist. Perioperative management and impact of desensitisation protocol are discussed.
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BACKGROUND AND AIMS: Accurate blood pressure measurements are the mainstay for the efficient management of abrupt cardiovascular changes during reperfusion in liver transplant. We sought to compare the femoral and radial pressures during reperfusion and at T1:baseline, T2: 1 h in dissection: T3:portosystemic shunt, T4:reperfusion, T5: at bile duct anastomosis. METHODS: A retrospective study was performed amongst 102 adult patients who underwent R lobe living donor liver transplantation. Mean arterial pressure (MAP) and systolic arterial pressure (SAP) at 10 s intervals at reperfusion and at five fixed time points were compared by intraclass correlation coefficient (ICC) and limits of agreement by Bland-Altman statistics. RESULTS: MAP by both routes had a good correlation at all time points during reperfusion (overall ICC: 0.946 [0.938, 0.949]) in comparison with SAP (overall ICC: 0.650 [0.6128, 0.684]). At the lowest reperfusion pressure (reperfusion point), MAP showed high levels of agreements (ICC: 0.833 [0.761, 0.885]), whereas SAP showed only a poor level of agreement (ICC 0.343 [0.153, 0.508]). The Bland-Altman analysis for MAP showed a bias of 7.18 (5.94) mmHg and limits of agreement of - 4.5 mmHg to + 18.8 mmHg and for SAP a bias of 25.2 (22.04) mmHg and limits of agreement of - 18.0 mmHg to + 68.4 mmHg at the reperfusion point. The incidence of post-reperfusion syndrome (PRS) was 52.94% by femoral and 57.84% by radial routes. CONCLUSIONS: Radial MAP correlated well with femoral MAP during reperfusion and at predefined time points and can be used interchangeably for intraoperative monitoring. A high incidence of PRS was noted by our technique of measurement.
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The novel coronavirus disease 2019 (COVID-19) pandemic has impacted health care worldwide, with specific patient populations, such as those with diabetes, cardiovascular disease, and chronic lung disease, at higher risk of infection and others at higher risk of disease progression. Patients with decompensated cirrhosis fall into the latter category and are a unique group that require specific treatment and management decisions because they can develop acute-on-chronic liver failure. In liver transplant recipients, the atypical immunity profile due to immunosuppression protects against downstream inflammatory responses triggered by COVID-19. This exhaustive review discusses the outcomes associated with COVID-19 in patients with advanced cirrhosis and in liver transplant recipients. We focus on the immunopathogenesis of COVID-19, its correlation with the pathogenesis of advanced liver disease, and the effect of immunosuppression in liver transplant recipients to provide insight into the outcomes of this unique patient population.
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BACKGROUND/OBJECTIVES: Although much has been learnt regarding pregnancy after liver transplantation, data from India are scant. Hence, we evaluated the maternal and fetal outcomes of pregnancies after liver transplantation at our center. METHODS: We conducted a retrospective review of all patients who underwent liver transplantation and later conceived at our center between 2006 and 2019. RESULTS: Of the 750 liver transplantations performed at our center, 129 were female and 62 of them were in the childbearing age group (15-44 years). A total of seven conceptions occurred in seven patients during the study period. All the pregnancies occurred spontaneously. The median age of the patients at the time of liver transplantation and conception was 25 years (range, 24-33 years) and 29 years (range, 26-36 years), respectively. The median interval between transplantation and conception was 40 months (range, 7-48 months). All patients were on tacrolimus monotherapy. None of the patients had rejection during pregnancy despite a low median tacrolimus trough level of 2.7 ng/mL. Live birth (five cesarean and one normal) occurred in six of seven pregnancies at a median gestation age of 37.5 weeks. Mean birth weight was 3055.8 g (range, 2470-3635 g). Antenatal rubella infection and grade III intrauterine growth restriction resulting in still birth at 29 weeks occurred in one patient. The median postnatal follow-up was 25 months (range, 2-81 months). All babies and mothers were healthy. CONCLUSIONS: Pregnancy after liver transplantation has a favorable outcome with a multidisciplinary team approach. There is a physiological reduction of tacrolimus trough levels during pregnancy for which dose augmentation is not usually required.
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BACKGROUND: The role of N-acetylcysteine (NAC) in improving outcomes following live donor liver transplantation (LDLT) is not well established. We designed a randomized double-blind placebo-controlled trial to study the role of NAC infusion in recipients undergoing LDLT. METHODS: We assigned 150 patients who underwent LDLT by computer-generated random sequence on 1:1 ratio to either NAC group or placebo group. Patients in the NAC group received NAC infusion which was started at beginning of graft implantation at an initial loading dose of 150 mg/kg/h over 1 h, followed by 12.5 mg/kg/h for 4 h and then at 6.25 mg/kg/h continued for 91 h. Placebo group received normal saline. The primary endpoint was composite occurrence of acute kidney injury (AKI) and early allograft dysfunction (EAD) in the recipient. Secondary endpoints included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, INR, primary graft non-function, intraoperative bleeding, post-transplant hospital stay and in-hospital mortality. RESULTS: The composite endpoint did not show any significant difference between the NAC and placebo group (21.3% vs 29.3%, p = 0.35). Peak AST (425.65 IU/L vs 702.24 IU/L, p = 0.02) and peak ALT (406.65 IU/L vs 677.99 IU/L, p = 0.01) levels were significantly lower in the study group. Time to normalization of transaminases was also significantly low in the study group. CONCLUSIONS: Perioperative NAC infusion following LDLT resulted in significantly lower postoperative AST and ALT levels. Rapid normalization of transaminases was also observed. This, however, did not translate to improvement in AKI or EAD.
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Injúria Renal Aguda , Transplante de Fígado , Acetilcisteína/uso terapêutico , Método Duplo-Cego , Humanos , Doadores VivosRESUMO
BACKGROUND: Although, ABO-incompatible (ABOi) liver transplantation is considered a high-risk procedure, using newer and more effective preoperative B cell desensitisation techniques, many transplant centres are routinely performing ABOi living donor liver transplantation (LDLT). METHODS: This was a retrospective study of 12 patients (adult:pediatric = 10:2; M:F = 9:3; median age, 45.5 years [range 1 to 56 years]) who underwent ABOi LDLT at a tertiary care centre. RESULTS: The median model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) scores were 28 (range 18 to 35) and 30.5 (range 24 to 37), respectively. For desensitisation, we initially used two doses of rituximab and two sessions of plasmapheresis preoperatively. We faced high mortality in the initial seven patients (five deaths) due to overwhelming sepsis from multidrug-resistant (MDR) pathogens. Subsequently, we restricted the rituximab to one dose and performed plasmapheresis only when isoagglutinin titre value was more than 1:64. With this regimen, out of the last five patients, four did well. For the whole cohort, the incidence of antibody-mediated rejection, acute cellular rejection, biliary complications, hepatic artery thrombosis, infection, and 5-year patient survival were 16.7%, 16.7%, 16.7%, 8.3%, 75%, and 40%, respectively. The risk factors for mortality were high MELD score, O blood group, and more intense desensitisation protocol. CONCLUSIONS: Careful selection of patients and less intense desensitisation protocol are probably important in improving the outcomes in ABOi LDLT.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Dessensibilização Imunológica/métodos , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado , Doadores Vivos , Plasmaferese , Rituximab/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Incidência , Índia/epidemiologia , Lactente , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Utilization of liver grafts from hepatitis B core antibody (anti-HBc) positive donors carries the risk of reactivation of hepatitis B virus (HBV) in recipients because of post-transplant immunosuppressive therapy. METHODS: This was a retrospective study of patients who had received liver grafts from anti-HBc positive live donors between 2006 and 2016 at our institute. RESULTS: Out of 22 recipients [all males, mean age 45.4 years (range 18-64 years)], four patients were hepatitis B surface antigen (HBsAg) positive preoperatively and received entecavir post-transplantation. One among these patients who temporarily stopped entecavir had a recurrence of hepatitis B 39 months post-transplantation. Among the 13 non-immune [hepatitis B surface antibody (anti-HBs) < 10 mIU/mL] recipients, eight were prescribed lamivudine (100 mg daily) as monoprophylaxis. Four compliant patients remain negative for HBV so far. Out of the remaining four, two died secondary to sepsis unrelated to hepatitis B; two were non-compliant and developed reactivation of hepatitis B. Lamivudine was missed out in five non-immune patients; three of them developed hepatitis B reactivation while two remain negative. Anti-HBs titer was immune in five patients. Over a period of 4 to 8 years follow up, three remain immune without prophylaxis, while two expired due to causes unrelated to hepatitis B. Following the detection of hepatitis B infection, five patients have been started on tenofovir 300 mg once daily. CONCLUSIONS: Anti-HBc positive liver grafts can be safely used for live donor liver transplantation. If the recipients are immune preoperatively, they can be merely followed up without HBV prophylaxis. However, it is extremely important to prophylactically treat the non-immune recipients with an antiviral agent lifelong.