Cold stress-induced ferroptosis in liver sinusoidal endothelial cells determines liver transplant injury and outcomes.

Although cold preservation remains the gold standard in organ transplantation, cold stress-induced cellular injury is a significant problem in clinical orthotopic liver transplantation (OLT). Because a recent study showed that cold stress activates ferroptosis, a form of regulated cell death, we investigated whether and how ferroptosis determines OLT outcomes in mice and humans. Treatment with ferroptosis inhibitor (ferrostatin-1) during cold preservation reduced lipid peroxidation (malondialdehyde; MDA), primarily in liver sinusoidal endothelial cells (LSECs), and alleviated ischemia/reperfusion injury in mouse OLT. Similarly, ferrostatin-1 reduced cell death in cold-stressed LSEC cultures. LSECs deficient in nuclear factor erythroid 2-related factor 2 (NRF2), a critical regulator of ferroptosis, were susceptible to cold stress-induced cell death, concomitant with enhanced endoplasmic reticulum (ER) stress and expression of mitochondrial Ca2+ uptake regulator (MICU1). Indeed, supplementing MICU1 inhibitor reduced ER stress, MDA expression, and cell death in NRF2-deficient but not WT LSECs, suggesting NRF2 is a critical regulator of MICU1-mediated ferroptosis. Consistent with murine data, enhanced liver NRF2 expression reduced MDA levels, hepatocellular damage, and incidence of early allograft dysfunction in human OLT recipients. This translational study provides a clinically applicable strategy in which inhibition of ferroptosis during liver cold preservation mitigates OLT injury by protecting LSECs from peritransplant stress via an NRF2-regulatory mechanism.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm.

Colorectal cancer is a leading cause of cancer-related mortality, with nearly half of the affected patients developing liver metastases. For three decades, liver resection (LR) has been the primary curative strategy, yet its applicability is limited to about 20% of cases. Liver transplantation (LT) for unresectable metastases was attempted unsuccessfully in the 1990s, with high rates of perioperative death and recurrence. There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques. A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60% chance of survival after five years. Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria, especially in the Norvegian SECA trials. This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases. The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced, highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Blood salvage and autotransfusion during orthotopic liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT. METHODS: Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. RESULTS: Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group. CONCLUSION: IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC.

Evaluation of Vitamin D Levels in Children With Liver Transplant.

OBJECTIVES: Vitamin D deficiency is common in pediatric chronic liver disease despite oral replacement. We evaluated vitamin D deficiency before and after liver transplant and the relationship between posttransplant and pretransplant vitamin D deficiency and graft rejection. MATERIALS AND METHODS: Pediatric recipients with chronic liver disease (N =138) were divided into 4 groups: cholestatic liver diseases, cirrhosis, metabolic disorders, and acute liver failure. Pretransplant and posttransplant vitamin D levels, liver function tests, Pediatric End-Stage Liver Disease scores, rejection activity index scores by graft liver biopsy, and posttransplant patient survival were recorded. RESULTS: There were 62 (45%) female and 76 (55%) male participants (mean transplant age, 6.1 ± 5.6 years). Pretransplant mean available vitamin D of 90 patients was 25.2 ± 20.9 ng/mL, with 36 (40%) within reference range. Posttransplant level for 109 patients was 27.3 ± 18 ng/mL, with 64 (58.7%) within reference range. Pretransplant and posttransplant levels were available for 61 patients, and mean pretransplant levels were lower than posttransplant levels (23.7 ± 19.3 vs 28.3 ± 16.9 ng/mL; P = .01). Patients with cholestatic liver disease had lower pretransplant vitamin D levels (P = .04), which disappeared after transplant. Pretransplant vitamin D levels were positively correlated with serum albumin levels (r = 0.20) in all patients and negatively correlated with total/direct bilirubin (r = 0.29 and r = -0.30) in those with liver diseases and cirrhosis. No correlations were found between pretransplant vitamin D levels and Pediatric End-Stage Liver Disease scores, rejection activity index scores, and posttransplant mortality. CONCLUSIONS: Vitamin D deficiency is prevalent in pediatric chronic liver disease before and after transplant, especially for cholestatic liver diseases. However, no association between vitamin D levels and liver graft rejection or patient survival was noted. We recommend close monitoring and individualized vitamin D supplementation before and after liver transplant.

Assessment of the need for routine intraoperative cell salvage in liver transplantation.

PURPOSE: This study aimed to assess the necessity of routine intraoperative cell salvage in liver transplantations. METHODS: A total of 327 liver transplants performed between 2014 and 2016 was included in the analysis. Patient data, including pre-transplant examinations, intraoperative red blood cell transfusions, and procedural information, were collected. RESULTS: The median age of the patients was 54 years old, with 67% (219) being male. The most prevalent ABO blood type was O, accounting for 48% (155) of cases. The leading causes of liver disease were hepatitis C (113 cases, 34.6%) and alcohol-related liver disease (97 cases, 29.7%). Out of the 327 liver transplants, allogeneic red blood cell transfusions were administered in 110 cases (34%) with a median of two units of red blood cells per case. Cell salvage was employed in 237 transplants (73%), and successful blood recovery was achieved in 221 cases (93%). Among the group that recovered more than 200 mL of blood, the median volume of recovered blood was 417 mL, with no transfusion of allogeneic blood required. A total of 90 transplants was performed without utilizing cell salvage, and, among these cases, 19 required blood transfusions, with a median of zero units transfused. CONCLUSIONS: This study suggests that routine cell salvage is unnecessary for all liver transplantations. The most suitable indication for its use is in patients presenting with portal vein thrombosis and abnormal creatinine levels.

Pharmacokinetics and Therapeutic Target Attainment of Meropenem in Pediatric Post-Liver Transplant Patients: Extended vs Intermittent Infusion.

PURPOSE: The aim of this study is to characterize the concentration-time profile, pharmacokinetics parameters, and therapeutic target attainment of meropenem in pediatric post-liver transplant patients according to the duration of infusion. METHODS: This is a prospective cohort of pediatric transplant recipients with preserved renal function receiving meropenem 40 mg/kg every 8 hours. The patients were stratified into 2 groups based on infusion duration: G1 (15 minutes of intermittent infusion) and G1 (3 hours of extended infusion). Two blood samples per child were collected during the same interval within 48 hours of starting the antimicrobial. Meropenem concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were assessed using a noncompartmental analysis. The therapeutic target was defined as 100% of the time above the minimum inhibitory concentration. FINDINGS: Fourteen patients with 28 measured meropenem concentrations were included. Lower values of volume of distribution and meropenem clearance compared with other critically ill pediatric populations were found. All patients achieved the therapeutic target against gram-negative pathogens with a minimum inhibitory concentration of ≤8 mg/L. Patients receiving a 15-minute infusion had higher values of peak and trough concentrations, resulting in unnecessary increased total drug exposure when compared to patients receiving a 3-hour infusion (P < .05). CONCLUSIONS: Meropenem at 120 mg/kg/d attained the therapeutic target against sensitive microorganisms in pediatric liver transplant recipients. The extended infusion should be preferred for patient safety. Because of the pharmacokinetic changes resulting from liver transplantation, individualized meropenem dosing regimens may be necessary.

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

Liver Transplantation for Acute Liver Failure Due to Yellow Phosphorus Poisoning - A Comprehensive Review.

Yellow phosphorus or metal phosphide (YP-MP) rodenticide poisoning has been a known cause of acute liver failure (ALF) in many countries of Asia and North and South America over the last decade. It is a highly toxic compound and is a well-known cause of intentional or accidental poisoning in both adults and children. In lower doses, it causes gastrointestinal symptoms and mild hepatic injury, and patients may spontaneously recover. In higher doses, hepatic necrosis and fatty infiltration may cause significant injury and may even lead to ALF, characterized by hepatic encephalopathy, coagulopathy, and lactic acidosis. Cardiotoxicity, rhabdomyolysis, and neutropenia are other well-documented complications. If untreated, it may lead to multi-organ dysfunction and death. Plasmapheresis and continuous renal replacement therapy (CRRT) have been used with limited success in patients who do not recover spontaneously. However, patients who develop ALF often need liver transplantation (LT). Liver transplantation has been successfully performed in ALF due to YP-MP poisoning in several countries, with good results in both adult and pediatric patients. Separate criteria for LT are important to ensure early and rapid listing of critical patients on the waiting list. The success rates of LT for ALF due to YP-MP rodenticide poisoning are very promising, provided there are no contra-indications to transplant. Plasma exchange, CRRT, or cytosorb can be used as a bridge to transplant in selected patients. In the long term, only with an increase in public awareness and sale restrictions can we prevent the intentional and accidental poisoning caused by this easily available, highly toxic compound.

Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation. / è‚ç§»æ¤æœ¯åŽé©å °æ°é˜³æ€§çƒèŒçš„æ„ŸæŸ“ç‰¹ç‚¹åŠé˜²æ²»æ•ˆæžœ.

OBJECTIVES: Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections. METHODS: In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed. RESULTS: Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001). CONCLUSIONS: Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Preferred language and disease severity predict evaluation for liver transplantation among patients admitted with alcohol-associated hepatitis.

BACKGROUND: Liver transplantation (LT) for alcohol-associated hepatitis (AH) is a relatively new practice and limited work exists surrounding the role social determinants of health may play in evaluation. This includes language that defines how patients interact with the healthcare system. We explored characteristics of patients with AH evaluated for LT within an integrated health system. METHODS: Using a system-wide registry, we identified admissions for AH from 1 January 2016 to 31 July 2021. A multivariable logistic regression model was developed to evaluate independent predictors of LT evaluation. RESULTS: Among 1723 patients with AH, 95 patients (5.5%) underwent evaluation for LT. Evaluated patients were more likely have English as their preferred language (95.8% vs 87.9%, P = 0.020), and had higher INR (2.0 vs 1.4, P < 0.001) and bilirubin (6.2 vs 2.9, P < 0.001). AH patients who underwent evaluation had a lower burden of mood and stress disorders (10.5% vs 19.2%, P < 0.05). Patients with English preferred language had a greater than three times adjusted odds of LT evaluation compared with all others when adjusting for clinical disease severity, insurance status, sex, and psychiatric comorbid conditions (OR, 3.20; 95% CI, 1.14-9.02). CONCLUSION: Patients with AH evaluated for LT were more likely to have English as their preferred language, more psychiatric comorbidities, and more severe liver disease. Despite adjustment for psychiatric comorbidities and disease severity, English preferred language remained the strongest predictor of evaluation. As programs expand LT for AH, it is vital to build equitable systems that account for the interaction between language and healthcare in transplantation.

Postoperative Supplemental Oxygen in Liver Transplantation (PSOLT) does not reduce the rate of infections: results of a randomized controlled trial.

BACKGROUND: Despite inconsistent evidence, international guidelines underline the importance of perioperative hyperoxygenation in prevention of postoperative infections. Further, data on safety and efficacy of this method in liver transplant setting are lacking. The aim was to evaluate efficacy and safety of postoperative hyperoxygenation in prophylaxis of infections after liver transplantation. METHODS: In this randomized controlled trial, patients undergoing liver transplantation were randomly assigned to either 28% or 80% fraction of inspired oxygen (FiO2) for 6 postoperative hours. Infections occurring during 30-day post-transplant period were the primary outcome measure. Secondary outcome measures included 90-day mortality, 90-day severe morbidity, 30-day pulmonary complications, durations of hospital and intensive care unit stay, and 5-day postoperative bilirubin concentration, alanine and aspartate transaminase activity, and international normalized ratio (INR) (clinicatrials.gov NCT02857855). RESULTS: A total of 193 patients were included and randomized to 28% (n = 99) and 80% (n = 94) FiO2. With similar patient, operative, and donor characteristics in both groups, infections occurred in 34.0% (32/94) of patients assigned to 80% FiO2 as compared to 23.2% (23/99) of patients assigned to 28% FiO2 (p = 0.112). Patients randomized to 80% FiO2 more frequently developed severe complications (p = 0.035), stayed longer in the intensive care unit (p = 0.033), and had higher bilirubin concentration over first 5 post-transplant days (p = 0.043). No significant differences were found regarding mortality, duration of hospital stay, pulmonary complications, and 5-day aspartate and alanine transaminase activity and INR. CONCLUSIONS: Postoperative hyperoxygenation should not be used for prophylaxis of infections after liver transplantation due to the lack of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02857855. Registered 7 July 2016.

Clinical analysis of Wernicke encephalopathy after liver transplantation.

BACKGROUND: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation. METHODS: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed. RESULTS: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia. CONCLUSIONS: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.

Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation / 中南大学学报(医学版)

OBJECTIVES@#Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections.@*METHODS@#In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed.@*RESULTS@#Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001).@*CONCLUSIONS@#Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Effect of cell salvage on bleeding, transfusion of blood products, and bleeding parameters in patients undergoing liver transplantation with intraoperative massive blood transfusion.

BACKGROUND: Autologous transfusion using a cell saver system has been used in liver transplantation with controversial outcomes. Its efficiency in patients with massive intraoperative transfusion has not been studied yet. This study aimed to evaluate effect of cell salvage (CS) on intraoperative bleeding and transfusion practices in liver transplantation with massive intraoperative transfusion. METHODS: Consecutive patients aged ≥18 years with intraoperative massive blood transfusion (≥ 6 units) between March 2014 and September 2020 were included. Patients subjected to CS were grouped as CS, whereas other patients were grouped as control. Number of transfused red blood cells was study's primary outcome. RESULTS: There were 38 and 32 patients in CS and control groups, respectively. Median blood loss was significantly lower in CS group than in control group (2500 mL vs. 4000 mL, p = 0.010). There were significantly more transfusions of red blood cells, fresh frozen plasma, platelets, and cryoprecipitates in CS group (p < 0.05). Postoperative median hemoglobin levels were determined as 4.8 g/dL and 8.2 g/dL in CS and control groups (p < 0.001). The decrease in postoperative hemoglobin levels compared to preoperative values was significantly higher in the CS group (p < 0.001). The mortality rate in postoperative first year was significantly higher in CS group than in control group (36.8% vs. 12.5%, p = 0.041). DISCUSSION: Use of CS in patients undergoing liver transplantation with massive intraoperative transfusion did not improve clinical and transfusion-related outcomes. In conclusion, its usage can be questionable given the absence of any clinical benefit and presence of poor outcomes.

The effect of taurine supplementation on delirium post liver transplantation: A randomized controlled trial.

BACKGROUND & AIMS: Delirium is a prevalent complication of liver transplantation (LT). It may enhance the risk of morbidity and mortality. Taurine is considered to have antioxidant and neuroprotective activities. The aim of this study was to evaluate taurine supplementation effect on post-LT delirium. METHODS: Patients older than 18 years old who had received LT in Abu-Ali Sina transplantation center in Shiraz, Iran from September 2020 to June 2021, were enrolled in this double-blinded randomized clinical trial. Exclusion criteria was known hypersensitivity to taurine, pregnancy or breast-feeding and death within 72 h post-LT. Patients were randomly divided into two groups, each received 2 g/day placebo or taurine from the first day post-LT for 30 days. Delirium was assessed using Confusion Assessment Method-Intensive Care Unit (CAM-ICU). Mortality and rejection rates and length of Intensive Transplantation Unit (ITU) and hospital stays were evaluated within one month after transplantation. RESULTS: Two hundred and seven patients were divided into two groups. Twenty-eight and 23 patients were excluded due to their refuse to participate in the study and death within 72 h post-LT, respectively. Delirium rate within the first month was 23.08% and was significantly lower in taurine group (9.46%) compared with placebo (35.36%, P = 0.012). Length of ITU stay was significantly higher among delirious patients (P = 0.015) in this analysis. CONCLUSION: we reached to the result that taurine can prevent post-LT delirium, dramatically. Placebo receiving and longer stay in ITU were the only independent risk factors in this trial. REGISTRATION NUMBER OF CLINICAL TRIAL: The study was registered at the Iranian Registry of Clinical Trials (IRCT20200312046755N1; http://www.irct.ir/).

Antithrombin supplementation for prevention of vascular thrombosis after pediatric liver transplantation.

AIMS: After liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential pro thrombotic imbalance. We studied the thrombotic and hemorrhagic complications in our pediatric LT series, providing supplementation of fresh frozen plasma (FFP) and/or antithrombin (AT) in the prophylactic antithrombotic regimen. METHODS: This was a retrospective observational single center study. All isolated pediatric LTs performed between 1/11/2009 and 31/12/2019 (n = 181) were included. Postoperatively, in addition to low molecular weight heparin, 22 patients (12%) received FFP (10 ml/kg twice daily for 10 days), 27 patients (15%) were given FFP (reduced duration) and AT (50-100 IU/kg/day if AT activity remained <70%), and 132 (73%) received AT only. Complications, outcome, and coagulation profiles in postoperative days 0-10 were analyzed. RESULTS: In all three treatment groups, AT activity normalized by day 4 while prothrombin remained <70% of normal until day 9. Hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and hemorrhagic complications occurred in 2.8%, 3.3%, and 3.9% of LTs. One- and 5-year patient and graft survival were 88% (±2.4% Standard Error) and 84% (±2.5%), and 86% (±2.6%) and 84% (±2.7%), respectively, without difference between groups. HAT were associated with low AT on days 0 and 1, and PVT with low AT on day 0. CONCLUSIONS: Low antithrombin activity after LT was associated with postoperative thromboses. FFP and/or AT supplementation allowed early normalization of AT activity, while thrombotic or hemorrhagic complications were rare, suggesting efficient and safe management of post-LT coagulopathy.

An Alternative Abdominal Closure Technique After Pediatric Liver Transplant: Bogota Bag Technique.

OBJECTIVES: In conditions such as large-for-size syndrome, postreperfusion hepatic edema, and intestinal edema, primary closure of the abdominal wall can cause respiratory complications and thrombosis of vascular structures. Here, we compared results of primary abdominal closure versus a temporary patch closure technique (the Bogota bag technique) in pediatric liver transplant recipients. MATERIALS AND METHODS: We performed primary abdominal closure in 295 recipients. In 39 pediatric liver transplant recipients, the Bogota bag technique was used as the abdominal closure technique because of suspected intraoperative tense abdominal closure. In patients who had the Bogota bag technique, we sutured the sterilized saline bag to the skin at the edge of the defect by shaping the defect so as not to cause abdominal hypertension. Primary abdominal closure was achieved in patients after control laparotomies at 48-hour intervals. RESULTS: The mean age of the primary abdominal closure group was 8.38 years, whereas the mean age of the Bogota bag group was 2 years. The average weight of patients in the primary abdominal closure group was 26.38 kg, and the average weight of patients in the Bogota bag group was 7.93 kg. Biliary atresia was the most common indication in both groups. Mean length of hospital stay was 21 days in the primary abdominal closure group and 24 days in Bogota bag group. Six patients in the Bogota bag group died from sepsis or bleeding in the early postoperative period. In the Bogota bag group, wound closure was achieved within 2 weeks in 25 patients and within 3 weeks in 8 patients. CONCLUSIONS: Temporary patch closure techniques can be used safely in low-weight and young children, children with large-for-size grafts, and those who display increased intra-abdominal pressure.

Management of Alcohol-Related Liver Disease and Its Complications.

Alcohol-related liver disease (ALD) is a major healthcare/economic burden and one of the leading causes of liver transplantation. New epidemiological studies that detail the course of the disease are needed since, despite its high prevalence, it is still a stigmatised condition with underlying pathology. Alcoholic hepatitis, as the highest expression of ALD, has high morbidity. Current treatments have suboptimal results with the exception of liver transplantation. Epidemiological studies must also be developed to improve prevention and implement early diagnosis policies. It is essential to develop multidisciplinary health models that allow the liver transplantation candidate to be approached in a holistic way, both for indication and follow up. The implementation of alcohol consumption biomarkers (ethyl glucuronide, phosphatidylethanol) can assist in diagnosing and supporting recovery. There are several initiatives with new therapies that must be validated to establish their effectiveness and indication.

Eight-Fold Increase in Dietary Supplement-Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States.

We investigated the trends in listing and outcomes of drug-induced acute liver failure (DIALF) over the last quarter century in the United States using the United Network for Organ Sharing (UNOS) database. We examined waitlisted patients in the UNOS database between 1995 and 2020 with a diagnosis of DIALF and assessed trends in etiologies, demographic and clinical characteristics, and outcomes over 3 periods: 1995-2003, 2004-2012, and 2013-2020. Patients with DIALF and cirrhosis were classified as drug-induced acute-on-chronic liver failure. Implicated agents including acetaminophen (APAP) and herbal or dietary supplements (HDSs) were ascertained. There were 2146 individuals with DIALF during the study period. The observed demographic trends between the earliest and latest period included fewer pediatric patients (18.8% to 13.5%) but with an increasing number of males in non-APAP DIALF (31.8% to 41.4%) and increased racial diversity in APAP DIALF. Antimicrobials remained the most common non-APAP agents across all periods, but antiepileptics, propylthiouracil, and mushroom poisoning decreased, while HDSs markedly increased from 2.9% to 24.1% of all non-APAP DIALF patients. The overall 5-year post-liver transplantation (LT) patient survival improved significantly over the 3 periods (69.9% to 77.4% to 83.3%) and was evident for both APAP and non-APAP DIALF. Over the last quarter century, there has been an 8-fold increase in HDS-related liver failure necessitating waitlisting for liver transplantation in the United States. There are other important temporal trends during the study period, including improved survival following LT among both APAP and non-APAP DIALF patients.