Intraoperative vascular air embolism and intracardiac thrombosis complicating liver transplantation: a case report.

BACKGROUND: Intracardiac thrombus and vascular air embolism represent rare complications in the context of orthotopic liver transplantation. While isolated reports exist for intracardiac thrombus and vascular air embolism during orthotopic liver transplantation, this report presents the first documentation of their simultaneous occurrence in this surgical setting. CASE PRESENTATION: This case report outlines the clinical course of a 60-year-old white female patient with end-stage liver disease complicated by portal hypertension, ascites, and hepatocellular carcinoma. The patient underwent orthotopic liver transplantation and encountered concurrent intraoperative complications involving intracardiac thrombus and vascular air embolism. Transesophageal echocardiography revealed the presence of air in the left ventricle and a thrombus in the right atrium and ventricle. Successful management ensued, incorporating hemodynamic support, anticoagulation, and thrombolytic therapy, culminating in the patient's discharge after a week. CONCLUSIONS: This report highlights the potential for simultaneous intraoperative complications during orthotopic liver transplantation, manifesting at any phase of the surgery. It underscores the critical importance of vigilant monitoring throughout orthotopic liver transplantation to promptly identify and effectively address these rare yet potentially catastrophic complications.

Combined Sleeve Gastrectomy with Liver Transplant in Patients with Obesity: a Feasibility Study.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) associated with obesity is one of the leading causes of liver failure requiring transplant, yet guidelines for the management of obesity in these scenarios are not always followed. In order to decrease incidence of NASH in the new liver, we studied the feasibility of simultaneous liver transplant and bariatric surgery. MATERIALS AND METHODS: We retrospectively identified patients who underwent simultaneous liver transplant and sleeve gastrectomy at our hospital site between November 24, 2019, and April 14, 2022. Demographics, surgical data, postoperative adverse events, and weight loss data were collected. RESULTS: Ten patients met inclusion criteria. Mean body mass index (BMI) at the time of transplant was 43.1 ± 5.3 kg/m2, and mean length of hospital stay was 10.8 ± 5.22 days. Within 30 days after surgery, 7 patients reported adverse effects, and 2 were readmitted. Mean BMI at 6-month follow-up was 30.6 ± 2.5 kg/m2. Mean percentage excess weight (in pounds) loss was 48.1 ± 11.4%, 58.6 ± 8.9%, and 66.1 ± 15.3% at 3-, 6-, and 12-month follow-up, respectively. Three patients had an increase in weight at 12-month follow-up when compared to 6-month follow-up. Most patients required fewer comorbidity-related medications, and none reported adverse effects related to sleeve gastrectomy. CONCLUSIONS: Bariatric surgery at the time of liver transplant is safe and has minimal adverse effects. Results include substantial postoperative weight loss, improvement in comorbidities, and decreased risk of NASH in the new liver. Further studies with larger cohorts are required to confirm the findings of this study.

Radiation Segmentectomy for the Treatment of Solitary Hepatocellular Carcinoma: Outcomes Compared with Those of Surgical Resection.

PURPOSE: To investigate the outcomes of radiation segmentectomy (RS) versus standard-of-care surgical resection (SR). MATERIALS AND METHODS: A multisite, retrospective analysis of treatment-naïve patients who underwent either RS or SR was performed. The inclusion criteria were solitary hepatocellular carcinoma ≤8 cm in size, Eastern Cooperative Oncology Cohort performance status of 0-1, and absence of macrovascular invasion or extrahepatic disease. Target tumor and overall progression, time to progression (TTP), and overall survival rates were assessed. Outcomes were censored for liver transplantation. RESULTS: A total of 123 patients were included (RS, 57; SR, 66). Tumor size, Child-Pugh class, albumin-bilirubin score, platelet count, and fibrosis stage were significantly different between cohorts (P ≤ .01). Major adverse events (AEs), defined as grade ≥3 per the Clavien-Dindo classification, occurred in 0 patients in the RS cohort vs 13 (20%) patients in the SR cohort (P < .001). Target tumor progression occurred in 3 (5%) patients who underwent RS and 5 (8%) patients who underwent SR. Overall progression occurred in 19 (33%) patients who underwent RS and 21 (32%) patients who underwent SR. The median overall TTP was 21.9 and 29.4 months after RS and SR, respectively (95% confidence interval [CI], 15.5-28.2 and 18.5-40.3, respectively; P = .03). Overall TTP subgroup analyses showed no difference between treatment cohorts with fibrosis stages 3-4 (P = .26) and a platelet count of <150 × 109/L (P = .29). The overall progression hazard ratio for RS versus SR was not significant per the multivariate Cox regression analysis (1.16; 95% CI, 0.51-2.63; P = .71). The median overall survival was not reached for either of the cohorts. Propensity scores were calculated but were too dissimilar for analysis. CONCLUSIONS: RS and SR were performed in different patient populations, which limits comparison. RS approached SR outcomes, with a lower incidence of major AEs, in patients who were not eligible for hepatectomy.

The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure.

BACKGROUND: Neoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated. METHODS: A single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed. RESULTS: Twenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17-88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3-33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3-10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9-46.8 months) from major hepatectomy and 37.6 months (range, 25.2-53.1 months) from TARE. CONCLUSIONS: Major hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.

Outcomes of Minimally Invasive Versus Open Major Hepatic Resection.

Introduction: Minimally invasive major hepatic resection (MIMHR) is increasingly being performed in tertiary centers using either hand-assisted laparoscopic surgery (HALS) or totally laparoscopic surgery (TLS). The outcomes data of MIMHR are scarce, especially in comparison to open major hepatic resection (OMHR). Our aim was to compare 90-day outcomes in major hepatic resections when minimally invasive approaches are attempted. Methods and Procedures: At our institution, minimally invasive liver resection was formally introduced in January 2007, initially using the HALS approach. Since then, the use of TLS approach has increased. We collected data on all patients who underwent major liver resection between January 2007 and December 2017 at our institution. In an intention to treat fashion, we then compared MIMHR to OMHR. Results: From January 2007 to December 2017, 669 patients underwent liver resection. Of these, 203 patients (30%) underwent major hepatic resection and MIMHR and OMHR were performed in 68 (33%) and 135 (67%) patients, respectively. The rate of conversion from minimally invasive to open was 30.9%. Overall, there were no significant differences in 90-day mortality (2.9% versus 1.5%; P = .499) or major complications (14.7% versus 14.8%; P = .985). MIMHR was associated with a shorter average postoperative hospital stay (6.2 days versus 7.9 days; P = .0110) and shorter average ICU stay (0.66 days versus 0.90 days; P = .0299) compared with OMHR. Conclusions: The minimally invasive approach to major liver resection is a safe and reasonable alternative to an open approach when performed by a surgeon experienced with the relevant surgical techniques. MIMHR may be associated with similar outcomes and a shorter postoperative hospital stay with no increase in 90-day postoperative complications to OMHR.

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.

Intraoperative Events in Liver Transplantation Using Donation After Circulatory Death Donors.

Liver grafts from donation after circulatory death (DCD) are a source of organs to decrease wait-list mortality. While there have been lower rates of graft loss, there are concerns of an increased incidence of intraoperative events in recipients of DCD grafts. We aim to look at the incidence of intraoperative events between recipients of livers from DCD and donation after brain death (DBD) donors. We collected data for 235 DCD liver recipients between 2006 and 2017. We performed a 1:1 propensity match between these patients and patients with DBD donors. Variables included recipient age, liver disease etiology, biological Model for End-Stage Liver Disease (MELD) score, allocation MELD score, diagnosis of hepatocellular carcinoma, and year of transplantation. DCD and DBD groups had no significant differences in incidence of postreperfusion syndrome (P = 0.75), arrhythmia requiring cardiopulmonary resuscitation (P = 0.66), and treatments for hyperkalemia (P = 0.84). In the DCD group, there was a significant increase in amount of total intraoperative and postreperfusion blood products (with exception of postreperfusion packed red blood cells) utilized (P < 0.05 for all products), significant differences in postreperfusion thromboelastography parameters, as well as inotropes and vasopressors used (P < 0.05 for all infusions). There was no difference in patient (P = 0.49) and graft survival (P = 0.10) at 1, 3, and 5 years. In conclusion, DCD grafts compared with a cohort of DBD grafts have a similar low incidence of major intraoperative events, but increased incidence of transient vasopressor/inotropic usage and increased blood transfusion requirements. This does not result in differences in longterm outcomes. While centers should continue to look at DCD liver donors, they should be cognizant regarding intraoperative care to prevent adverse outcomes.

Looking inward: The impact of operative time on graft survival after liver transplantation.

BACKGROUND: Operative time often has been cited as an important factor for postoperative outcomes. Despite this belief, most efforts to improve liver transplant outcomes have largely focused on only patient and donor factors, and little attention has been paid on operative time. The primary objective of this project was to determine the impact of operative time on graft survival after liver transplant. METHODS: A retrospective review of 2,877 consecutive liver transplants performed at a single institution was studied. Data regarding recipient, donor, and operative characteristics, including detailed granular operative times were collected prospectively and retrospectively reviewed. Using an instrument variable approach, Cox multivariate modeling was performed to assess the impact of operative time without the confounding of known and unknown variables. RESULTS: Of the 2,396 patients who met the criteria for review, the most important factors determining liver transplant graft survival included recipient history of Hepatitis C (hazard ratio 1.45, P = .02), donor age (hazard ratio 1.23, P = .03), use of liver graft from donation after cardiac death donor (hazard ratio 1.50, P < .01), and operative time (hazard ratio 1.26, P = .01). In detailed analysis of stages of the liver transplant operation, the time interval from incision to anhepatic phase was associated with graft survival (hazard ratio 1.33; P = .02). CONCLUSION: Using a novel instrument variable approach, we demonstrate that operative time (in particular, the time interval from incision to anhepatic time) has a significant impact on graft survival. It also seems that some of this efficiency is under the influence of the transplant surgeon.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center

ABSTRACT Introduction and aim. Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. Material and methods. We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. Results. From 2003-2014,978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 -1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. Conclusions. In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center.

INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 - 1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. CONCLUSIONS: In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Wait Time of Less Than 6 and Greater Than 18 Months Predicts Hepatocellular Carcinoma Recurrence After Liver Transplantation: Proposing a Wait Time "Sweet Spot".

BACKGROUND: It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes. METHODS: This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012. RESULTS: Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis. CONCLUSIONS: This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant.

IMPORTANCE: Several factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence. OBJECTIVE: We aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging. DESIGN, SETTING, AND PARTICIPANTS: Predictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California-San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index. MAIN OUTCOMES AND MEASURES: Characteristics associated with post-LT HCC recurrence. RESULTS: A total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P < .001). In the development cohort of 721 patients (542 men), median α-fetoprotein (AFP) level at the time of LT was 8.3 ng/mL; 9.4% had microvascular invasion (n = 68), and 22.1% were beyond Milan criteria on explant (n = 159) owing to understaging by pretransplantation imaging. Cumulative probabilities of HCC recurrence at 1 and 5 years were 5.7% and 12.8%, respectively. On multivariable Cox proportional hazards regression, 3 variables were independently associated with HCC recurrence: microvascular invasion, AFP at time of LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RETREAT score was created using these 3 variables, with scores ranging from 0 to 5 or higher that were highly predictive of HCC recurrence (C statistic, 0.77). RETREAT was able to stratify 5-year post-LT recurrence risk ranging from less than 3% with a score of 0 to greater than 75% with a score of 5 or higher. The validation cohort (n = 340; 283 men) had significantly higher microvascular invasion (23.8% [n = 81], P < .001), explant beyond Milan criteria (37.3% [n = 159], P < .001), and HCC recurrence at 5 years (17.9% [n = 159], P = .03). RETREAT showed good model discrimination (C statistic, 0.82; 95% CI, 0.77-0.86) and superior recurrence risk classification compared with explant Milan criteria (net reclassification index, 0.40; P = .001) in the validation cohort. CONCLUSIONS AND RELEVANCE: We have developed and validated a simple and novel prognostic score that may improve post-LT HCC surveillance strategies and help identify patients who may benefit from future adjuvant therapies.

Hepatic Resection for Metastatic Neuroendocrine Cancer in Patients with Bone Metastases.

BACKGROUND: Hepatic resection (HR) of metastatic neuroendocrine cancer has been associated with prolonged survival and durable symptom control for selected patients with metastatic neuroendocrine tumor (NET). The present study investigates the outcomes of this operative approach in selected patients with known bone metastases. METHODS: All patients undergoing HR at Mayo Clinic Rochester and Mayo Clinic Florida for metastatic NET between January 1989 and August 2015 were identified, and were divided into two groups: those undergoing HR with a known diagnosis of bone metastases (HRmNET/LB) and those who had metastatic disease confined to the liver (HRmNET/L). RESULTS: A total of 25 patients in the HRmNET/LB group were propensity matched with 100 patients in the HRmNET/L group. Major liver resection was performed in 60 % of patients in the HRmNET/LB group and 55 % of patients in the HRmNET/L group (p = 0.42). Median survival for the HRmNET/LB group was 54.0 months, compared with 97.7 months for the HRmNET/L group (p = 0.03). In the HRmNET/LB group, median survival was 73.3 months for patients with gastrointestinal NET(GNET), compared with 42.7 months for patients with pancreatic NET (PNET). The median number of bone metastases was 2 (range 1-10), and the sites of bone metastases were the spine (68 %), pelvis (24 %), and ribs (12 %). Bone metastases were treated with radiotherapy in ten (40 %) patients, by radiofrequency ablation in two (8 %) patients, and by resection in one (4 %) patient. CONCLUSIONS: The present study is the first report to describe HR for patients with metastatic NET and known bone metastases. We demonstrated that in properly selected cases, excellent survival can be achieved with liver debulking in these patients.

Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations.

Identification of a molecular signature unique to metal-reducing Gammaproteobacteria.

Functional genes required for microbial (dissimilatory) metal reduction display high sequence divergence, which limits their utility as molecular biomarkers for tracking the presence and activity of metal-reducing bacteria in natural and engineered systems. In the present study, homologs of the outer membrane beta-barrel protein MtrB of metal-reducing Gammaproteobacteria were found to contain a unique N-terminal CXXC motif that was missing from MtrB homologs of nonmetal-reducing Gammaproteobacteria and metal- and nonmetal-reducing bacteria outside the Gammaproteobacteria. To determine whether the N-terminal CXXC motif of MtrB was required for dissimilatory metal reduction, each cysteine in the CXXC motif of the representative metal-reducing gammaproteobacterium Shewanella oneidensis was replaced with alanine, and the resulting site-directed mutants were tested for metal reduction activity. Anaerobic growth experiments demonstrated that the first, but not the second, conserved cysteine was required for metal reduction by S. oneidensis. The ability to predict metal reduction by Gammaproteobacteria with unknown metal reduction capability was confirmed with Vibrio parahaemolyticus, a pathogen whose genome encodes an MtrB homolog with an N-terminal CXXC motif. MtrB homologs with an N-terminal CXXC motif may thus represent a molecular signature unique to metal-reducing members of the Gammaproteobacteria.

Laparoscopic cholecystectomy in the cirrhotic patient: predictors of outcome.

BACKGROUND: We sought to determine the outcome predictors of 94 cirrhotic patients undergoing laparoscopic cholecystectomy (LC). METHODS: We performed a single-center, retrospective review of cirrhotic patients undergoing LC for symptomatic gallbladder disease. Statistical analysis was completed using the Chi-square, Wilcoxon rank-sum, and Student t tests as appropriate. RESULTS: Ninety-four procedures were completed. The median Child-Turcotte-Pugh (CTP) score was 6 (range, 5-12), and the average Model for End-Stage Liver Disease (MELD) score was 11 ± 5. Hepatitis C was the most common etiology of liver disease (50%) followed by Laennec's cirrhosis (22%). The average length of stay was 2.6 ± 4.3 days; 21% were outpatient procedures. The conversion rate was 11%. Conversion risk factors were decreased serum albumin, increased MELD score, and blood loss. Morbidity occurred in 32 patients. Predictors of morbidity were decreases in serum albumin, increases in International Normalized Ratio (INR) and CTP score, and the number of intraoperative red blood cell transfusions. Mortality occurred in 4 patients. Increased INR, CTP score, CTP class, the number of intraoperative blood and platelet transfusions were predictors of mortality. CONCLUSION: LC can be safely performed in cirrhotic patients with appropriate patient selection. Liver synthetic function, operative blood loss, transfusion requirement, CTP, and MELD scores may be used to predict outcomes in these patients.

Interleukin-33 is hepatoprotective during liver ischemia/reperfusion in mice.

UNLABELLED: Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. In the current study, we sought to determine whether IL-33 is an important regulator in the hepatic response to ischemia/reperfusion (I/R). Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia, followed by up to 8 hours of reperfusion. Some mice received recombinant IL-33 (IL-33) intraperitoneally (IP) before surgery or anti-ST2 antibody IP at the time of reperfusion. Primary hepatocytes and Kupffer cells were isolated and treated with IL-33 to assess the effects of IL-33 on inflammatory cytokine production. Primary hepatocytes were treated with IL-33 to assess the effects of IL-33 on mediators of cell survival in hepatocytes. IL-33 protein expression increased within 4 hours after reperfusion and remained elevated for up to 8 hours. ST2L protein expression was detected in healthy liver and was up-regulated within 1 hour and peaked at 4 hours after I/R. ST2L was primarily expressed by hepatocytes, with little to no expression by Kupffer cells. IL-33 significantly reduced hepatocellular injury and liver neutrophil accumulation at 1 and 8 hours after reperfusion. In addition, IL-33 treatment increased liver activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), cyclin D1, and B-cell lymphoma 2 (Bcl-2), but reduced serum levels of CXC chemokines. In vitro experiments demonstrated that IL-33 significantly reduced hepatocyte cell death as a result of increased NF-κB activation and Bcl-2 expression in hepatocytes. CONCLUSION: The data suggest that IL-33 is an important endogenous regulator of hepatic I/R injury. It appears that IL-33 has direct protective effects on hepatocytes, associated with the activation of NF-κB, p38 MAPK, cyclin D1, and Bcl-2 that limits liver injury and reduces the stimulus for inflammation.

Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells.

BACKGROUND AND AIM: The purpose of the present study was to determine the effects of interleukin-37 (IL-37) on liver cells and on liver inflammation induced by hepatic ischemia/reperfusion (I/R). METHODS: Mice were subjected to I/R. Some mice received recombinant IL-37 (IL-37) at the time of reperfusion. Serum levels of alanine aminotransferase, and liver myeloperoxidase content were assessed. Serum and liver tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemokine (KC) were also assessed. Hepatic reactive oxygen species (ROS) levels were assessed. For in vitro experiments, isolated hepatocytes and Kupffer cells were treated with IL-37 and inflammatory stimulants. Cytokine and chemokine production by these cells were assessed. Primary hepatocytes underwent induced cell injury and were treated with IL-37 concurrently. Hepatocyte cytotoxicity and Bcl-2 expression were determined. Isolated neutrophils were treated with TNF-α and IL-37 and neutrophil activation and respiratory burst were assessed. RESULTS: IL-37 reduced hepatocyte injury and neutrophil accumulation in the liver after I/R. These effects were accompanied by reduced serum levels of TNF-α and MIP-2 and hepatic ROS levels. IL-37 significantly reduced MIP-2 and KC productions from lipopolysaccharide-stimulated hepatocytes and Kupffer cells. IL-37 significantly reduced cell death and increased Bcl-2 expression in hepatocytes. IL-37 significantly suppressed TNF-α-induced neutrophil activation. CONCLUSIONS: IL-37 is protective against hepatic I/R injury. These effects are related to the ability of IL-37 to reduce proinflammatory cytokine and chemokine production by hepatocytes and Kupffer cells as well as having a direct protective effect on hepatocytes. In addition, IL-37 contributes to reduce liver injury through suppression of neutrophil activity.