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Purpose: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation., Methods: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion., Results: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1)., Conclusions: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.

Background: Hepatic artery thrombosis is the most common vascular complication of liver transplantation. When occurring late in the postoperative course, it may have no clinical repercussions, and conservative treatment may be implemented. Some patients, however, will develop severe biliary complications due to ischemic cholangiopathy and require retransplantation. The aim of this study is to report the outcomes of retransplantation in this population., Methods: This is a single-center retrospective study involving all adult patients who underwent liver retransplantation due to late hepatic artery thrombosis from January/2010 to December/2022., Results: During the study period, 1378 liver transplants were performed in our center; 147 were retransplantations, with 13 cases of late hepatic artery thrombosis (0.94%). All had symptomatic ischemic cholangiopathy. Twelve of them had already presented previous cholangitis, bilomas, or liver abscesses and had undergone biliary stenting or percutaneous drainage. The median time between the first liver transplant and late hepatic artery thrombosis diagnosis and between this diagnosis and retransplantation were 73 and 50 days, respectively. Arterial reconstruction using splenic artery, celiac trunk, or arterial conduit from the aorta was performed in 7 cases, whereas biliary reconstruction was mostly done with choledochojejunostomy (n = 8). There were 4 perioperative deaths, 2 due to primary non-function and 2 due to refractory shock after exceedingly complex retransplants., Conclusion: Liver retransplantation due to late hepatic artery thrombosis is a rare condition that should be offered to patients who develop severe biliary complications and recurrent infections. It is nonetheless a challenging procedure associated with significant perioperative mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers., Objective: The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly., Methods: This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023., Results: A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P = .002 and 50% vs 0%, P = .004, respectively)., Conclusion: Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Summary: People with cirrhosis of the liver are at risk for complications that can worsen their quality of life and increase morbidity and mortality. Contrary to previous beliefs, cirrhosis does not protect against the development of thromboembolic events, and cirrhotic patients may have higher rates of deep vein thrombosis (DVT)., Background and Aims: The study of chronic venous disease and its impact on patients with cirrhosis is unknown in the literature and may be an important fact since this condition also had impact on quality of life and morbidity. The aim of this study is to evaluate the prevalence of DVT (Deep Venous thrombosis) in outpatients with cirrhosis and the degree of chronic venous insufficiency, evaluating possible correlations between clinical and laboratory aspects of cirrhotic patients with these pathologies., Methods: Patients with cirrhosis were evaluated in the outpatient clinic of the Liver Transplantation and Hepatology Service of HC-FMUSP from November 2018 to November 2022, with clinical evaluation, venous disease questionnaires, data collection of imaging and laboratory tests, and venous color Doppler ultrasound. The information was analyzed by the University of São Paulo (USP) Statistics Department., Results: There was a prevalence of 7.6% of DVT in studied patients, VCSS score 6.73 and severe CEAP classification (C4-6) 32.1%. There was no association of DVT with qualitative variables by the Fisher test such as Child Turcotte Pugh Scale (CTP) ( p = 0.890), dichotomized INR values ( p = 0.804), etiology of cirrhosis ( p = 0.650) and chronic kidney disease ( p > 0.999), nor with quantitative variables by t-student's such as age ( p = 0.974), Body Mass Index (BMI) ( p = 0.997), MELD score ( p = 0.555), Albumin ( p = 0.150) and Platelets ( p = 0.403). We found that as the severity of ascites increases, there is an increase in the proportion of patients classified in the category indicating more severe clinical manifestations of chronic venous disease (C4 to C6). The mean age (54 years) was higher in patients with DVT than in those without. The mean BMI of patients without DVT (25.7 kg/m 2 ) is lower than that of patients with DVT (27.0 kg/m 2 ). The prevalence of DVT is higher in patients with thrombophilia (20.0%) than in those without (7.0%). This suggests an association between the two variables. The descriptive measures of the MELD score, the cirrhosis scale used for liver transplant waiting lists, did not indicate an association of this scale with the occurrence of DVT., Conclusion: The incidence of VTE (Venous Thromboembolic Events) and CVD (Chronic Venous Disease) within the sample surpassed that of the general population; nevertheless, more studies are required to validate these results. Concerning venous thromboembolism, no correlation was observed between the variables within the sample and the augmented risk of VTE. Regarding chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales. Statistical dispersion methods suggest that patients with higher BMI and more severe liver disease (according to the Child-Pugh score) are more likely to experience worsening of CVD. About chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 da Cruz Renó, Tustumi, Waisberg, Santos, Pinheiro, Macedo, Nacif, Ducatti, De Martino, Trevisan, D’Albuquerque and Andraus.)

Background: Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disorders. Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats., Donor Operation: We performed a perineal (including the genitalia, anus, muscles, and ligaments) and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian (female), or penile, testis and its ducts (male) was removed en bloc , flushed, and cold-stored., Recipient Operation: The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery., Results: We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2 h after transplantation., Conclusion: The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Galvao, Araki, Fonseca, Cruz, Lanchotte, Waisberg, Chaib, Nacif, Traldi, Mello, Andraus and Carneiro-D'Albuquerque.)

Background: Isolated intestinal transplantation (IT) is indicated in cases of intestinal failure (IF) in the absence of severe liver dysfunction. Short bowel syndrome (SBS) is the most frequent IF etiology, and due to the absence or considerable reduction of intestinal loops in the abdominal cavity in these patients, there is atrophy and muscle retraction of the abdominal wall, leading to loss of the abdominal domain and elasticity and preventing the primary closure of the abdominal wall. This study aimed to describe a technique for the closure of the abdominal wall after IT without using prostheses., Methods: Four patients underwent IT with the impossibility of primary closure of the abdominal wall. We describe a novel technique, associating a series of vacuum-assisted closure dressings, components separation, and relaxation incisions., Results: All patients presented a successful closure of the abdominal wall with the described technique, with no complications related to the abdominal wall., Conclusion: The technique proved to be safe, effective, and reproducible as an option for abdominal wall closure after IT. Employing this technique in a greater number of cases is necessary to confirm these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pinheiro, Andraus, Fortunato, Galvão, Nacif, Waisberg, Arantes, Lee, Rocha-Santos, Martino, Ducatti, Haddad, Bezerra and Carneiro-D'Albuquerque.)

BACKGROUND Adequate donor and recipient matching in liver transplantation is crucial to improve patient survival. Our objective was to propose and validate a new model for predicting outcomes using donor and recipient scoring criteria. MATERIAL AND METHODS We retrospectively analyzed data of all patients (n=932) who underwent liver transplantation (n=1106) from January 2006 to December 2018. For score standardization, 30% (n=280) of patients were randomly selected for analysis and divided into 3 categories: ≤4 points, 5 to 8 points, and >8 points. Scoring system validation was performed on a dataset with 70% (n=652) of the patients. RESULTS Survival of the stratified group (30%) was significant (P<0.001). Scores of 4 to 8 points presented lower risk of death (1.74 [CI 0.97-3.13; P=0.062]), while >8 points presented higher risk (2.74 [CI 1.36-5.57; P=0.005]). In the validation score (70%), global survival was significant (P<0.0016); patients with scores of 4 to 8 points had lower risk of death (1.16 [CI 1.16-2.38; P=0.005]); and scores >8 points (2.22 [CI 1.40-3.50; P<0.001]), retransplant, fulminant hepatitis, previous large abdominal/biliary tree surgery, MELD score, and serum creatinine before liver transplantation >1.5 mg/dL (P<0.05) presented higher risk. Individual recipient factors with 4 to 8 points had a lower risk of death (2.29 [CI 1.82-2.87; P<0.0001]) than those with scores >8 points (4.02 [CI 2.22-7.26; P<0.0001]). CONCLUSIONS A novel prognostic-based scoring system using donor and recipient characteristics was proposed and clinically validated. Two-factor scoring indicated the superiority of the predictability outcome and improved prediction of higher mortality.

Background: The classic piggyback technique uses the union of the 3 hepatic veins to perform the cavo-caval anastomosis. However, due to the lateral localization of the right hepatic vein, the partial clamping of the vena cava in this technique significantly reduces the venous return to the right atrium. To avoid this, we adopted in 2015 a modified piggyback technique, in which we use the common trunk of the middle and left hepatic veins and also perform a lateral incision toward the right in the anterior wall of the vena cava in order to widen the final ostium of the cavo-caval anastomosis. The aim of the study was to analyze the incidence of hepatic venous outflow obstruction between those 2 techniques., Methods: Retrospective study of liver transplant recipients undergoing venography for suspected hepatic venous outflow obstruction from January 2009 to June 2021. Patients undergoing transplantation with living donors or split grafts and pediatric cases were excluded from the study., Results: From January 2009 to December 2014 and from January 2015 to June 2021, 587 (group 1) and 730 (group 2) deceased-donor liver transplants were performed with the classic and the modified piggyback techniques, respectively. The incidence of cases with suspected hepatic venous outflow obstruction in groups 1 and 2 were 1.87% (n = 11) and 0.95% (n = 7), respectively (P = 0,15). The number of confirmed patients with outflow blockage that required endovascular treatment during venography in groups 1 and 2 were 4 (0.68%) and 5 (0.68%), respectively (P = 0,31)., Conclusions: This modified piggyback technique did not increase the incidence of hepatic venous outflow obstruction at our service., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The number of elderly patients who have end-stage liver disease and require liver transplantation has dramatically increased. On the other hand, liver grafts from elderly donors have been offered more frequently for transplantation. The present study aims to analyze the results of liver transplants performed with donors and recipients aged ≥70 years., Methods: We performed a single-center retrospective study of deceased donors liver transplants that involved recipients aged ≥7070 years or recipients who received grafts from donors aged ≥70 years from 2011 to 2021. A literature review on the results of liver transplantation in elderly recipients was also performed., Results: Thirty septuagenarian recipients were included; their overall 1- and 5-years survival was 80% and 76.6%, respectively. The prevalence of recipients aged ≥70 years in our department was 2.65%. Twenty recipients received grafts form septuagenarian donors; their overall 1- and 5-years survival was 75%. The prevalence of donors aged ≥70 years in our department was 1%. In the literature review, 17 articles were analyzed. The 5-years survival of recipients aged ≥70 years ranged from 47.1% to 78.5%., Conclusions: Septuagenarian recipients and patients who received grafts from elderly brain-dead donors present adequate overall survival after liver transplantation. Optimized donor-recipient matching is paramount for achieving good outcomes. The combination of high-risk donors with septuagenarian recipients should be avoided as well as using grafts of elderly donors that present others risk factors. Thus, the age of the donor or recipient alone cannot be considered an absolute contraindication for liver transplantation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Donor hepatic artery thrombosis (dHAT) identified during liver procurement and backtable is a rare and little-reported event that can make liver transplants unfeasible., Methods: This is a retrospective study of dHAT identified during liver grafts procurements or backtable procedures. All grafts were recovered from brain-dead donors. The demographic characteristics of the donors and the incidence of dHAT were analyzed. The data were also compared to a cohort of donors without dHAT., Results: There was a total of 486 donors during the study period. The incidence of dHAT was 1.85% (n = 9). The diagnosis of dHAT was made during procurement in 5 cases (55.5%) and during the backtable in 4 (44.4%). Most donors were female (n = 5), with an average BMI of 28.14 ± 6.9 kg/m 2 , hypertensive (n = 5), and with stroke as cause of brain death (n = 8). The most prevalent site of dHAT was a left hepatic artery originating from the left gastric artery (n = 4). Of the 9 cases reported, 2 livers were used for transplantation, and 7 were discarded. Comparing those cases to a cohort of 260 donors without dHAT, we found a higher incidence of anatomic variations in the hepatic artery (P = .01) and of stroke as cause of brain death (P = .05)., Conclusion: The occurrence of dHAT before liver procurement is a rare event, however it may become a treacherous pitfall if the diagnosis is late. Grafts with anatomic variations recovered from women with brain death due to stroke and with past history of hypertension seem to be at a higher risk of presenting dHAT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Terlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge., Case Report: A 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease-Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event., Conclusions: We described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest with regards to the content of this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Living donor liver transplant (LDLT) is a valuable therapeutic option for overcoming the deceased donor shortage. Modified right lobe graft (MRLG) keeps the middle hepatic vein (MHV) trunk with the remnant liver to improve donor safety. Hemostasis in the MHV tributary reconstruction can be tricky; surgical stitches and energy coagulation are ineffective. Fibrin glues are excellent vascular sealants but are poor in maintaining hemostasis in an active hemorrhage or preventing resection surface-related complications after liver resection. We propose applying fibrin sealant during back table graft preparation to seal the hepatic edge and MHV reconstruction to avoid bleeding after graft revascularization., Methods: Our retrospective cohort study included all adult patients undergoing LDLT between August 2017 and December 2021. During the back table procedure, we performed the reconstruction of the inferior right hepatic vein and/or MHV tributaries from segment 5 (V5) and segment 8 (V8) using a vein harvested from a nonrelated deceased donor. Before initiating the hepatic graft implantation, we applied fibrin sealant in the resected parenchyma, especially in the V5 and V8 anastomosis, to seal the hepatic edge and hepatic vein reconstruction., Results: No bleeding was identified in the hepatic edge, and blood product transfusion was unnecessary for any recipients after reperfusion., Conclusion: In LDLT using MRLG with MHV reconstruction, the fibrin sealant, when applied on the raw hepatic surface, and vascular reconstruction during back table graft preparation avoided bleeding after graft revascularization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Liver transplantation in an animal model is challenging due to hemodynamics and intraoperative anesthetic care. Several models are described in the literature employing different techniques such as venovenous bypass or aortic cross-clamping to maintain hemodynamic stability, although few groups keep the animal alive in the postoperative period. This study aims to evaluate a liver transplantation clinical model in pigs without venovenous bypass or aortic cross-clamping., Methods: Male pigs weighing 20 to 35 kg underwent liver transplantation surgery without using venovenous bypass or aorta cross-clamping. Protocols were approved by the Animal Care and Use Committee of the University of São Paulo, Brazil., Results: Ten LTs were performed. Cold ischemia and warm ischemia were 119 ± 33.28 minutes and 26 ± 9.6 minutes, respectively. Hemodynamic changes were significantly higher after the postrevasculazation phase: heart rate (P < .001), medium arterial pressure (P < .001), and cardiac output (P = .03). Hypotension was treated with intravenous fluids and, in some cases, with vasoactive drugs especially during the post-reperfusion period. No animals died during the procedure and almost survival until the first postoperative day. Serum aspartate aminotransferase and lactate increased their values in the post-reperfusion phase., Conclusions: Practice-based on laboratory animals improves surgical skills and the development of experimental models aimed at new advances in this field. Perfecting our technique on the swine model, we could move forward to create a small-for-size model, test new therapeutic strategies, and define the boundaries for safely performing an enlarged liver resection or a partial liver graft transplant., (Copyright © 2022. Published by Elsevier Inc.)

Background: Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching., Methods: Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT)., Results: Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P = .001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P = .004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P = .000), and recipient age >60 years (OR, 1.86; 95% CI, 1.27-2.73; P = .001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P = .003). Donor intensive care unit time >7 days (OR, 1.46; 95% CI, 1.04-2.06; P = .02) was also associated with overall mortality., Conclusions: We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality., (Copyright © 2022. Published by Elsevier Inc.)

Background: Identifying anatomic variations of the hepatic artery is essential in liver transplantation. The artery supply is crucial for the procedure's success, and, in some cases of anatomic variations, they need reconstruction. Hepatic artery thrombosis is a severe vascular complication. This study evaluated the prevalence of anatomic variations and correlated arterial reconstructions with hepatic artery thrombosis., Methods: We performed a retrospective analysis of medical records, adult patients undergoing liver transplant, donor's arterial anatomy, arterial reconstructions, and thrombosis after transplant from January 2019 to December 2020., Results: Among 226 cases, 71% had normal anatomy. All these patients met Michel's classification subtypes, of which 161 (71%) were class I, which is the most common. The second most common variation was class II, with 25 donors (11%), followed by class III, with 17 donors (7.5%). Anatomic artery variations were a risk factor for hepatic artery thrombosis development (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1-22.5; P = .002). In the same way, the artery reconstruction was associated with hepatic artery thrombosis arising with postoperative time (OR, 18.0; 95% CI, 4.9-57.5; P < .001). Global hepatic artery thrombosis occurred in 11 cases (4.87%)., Conclusion: Anatomic hepatic artery variations are frequent and do not make liver transplant unfeasible. However, variations that require reconstruction may raise the risk of thrombosis., (Copyright © 2022. Published by Elsevier Inc.)

Background: COVID-19 has spread worldwide and has become a public health emergency and a pandemic of international concern. The solid organ donation system was no different. This study aimed to investigate the effect of COVID-19 on the liver transplant (LT) system in Brazilian territory., Methods: We retrospectively reviewed all liver donor records allocated in São Paulo State, Brazil, 1 year before and 1 year during the COVID-19 pandemic. We defined the pre-COVID-19 (PRE) period as between April 2019 and April 2020 and the post-COVID-19 (POST) period as between April 2020 and April 2021. Moreover, we compared LT performed in our institution during these periods. To evaluate outcomes, we compared 30-day survival after LT., Results: In the PRE period, 1452 livers were offered for donation in São Paulo State and other Brazilian territories. Of these, 592 were used in LT. In the POST period, 1314 livers were offered for donation, but only 477 were used in LT. Organ refusal was higher in the POST period (P < .05). Our center performed 127 and 156 LTs in these periods, respectively, and an increase above 20% was significant (P = .039). There was no difference in 30-day survival between the periods (87.2% vs 87.9%, P > .5, respectively)., Conclusions: The COVID-19 pandemic harmed potential and allocated donors and LTs performed. However, it is possible to maintain the LT volume of a transplant center without compromising survival outcomes through preventive strategies against COVID-19 propagation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM)., Methods: We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION"., Results: Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process., Conclusions: The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided., (Copyright © 2022. Published by Elsevier Inc.)

Background: Pancreas transplantation remains a challenging procedure for small and medium-sized transplants teams, despite improvements in graft survival. Data regarding the impact of the procurement team's experience on the outcomes of pancreas transplant are lacking. The objective of this study was to evaluate risk factors that lead to pancreatic allograft thrombosis, especially the experience of the pancreas procurement team., Methods: A retrospective study of 137 patients who underwent pancreas transplantation between March 2005 and May 2017 was conducted. Donor's and recipient characteristics were evaluated as well as their relationship to pancreatic allograft thrombosis. Cases were divided according to the number of pancreas procurements previously done by the procurement surgeon: group 1 (30 to 40 retrievals) and group 2 (≥40 retrievals)., Results: Simultaneous pancreas-kidney transplants accounted for 89.8% of cases (n = 123). Surgeons from group 2 performed 62.8% (n = 86) of the procurements. The graft was removed in 19 cases (13.8%) due to thrombosis. In univariate analysis, lower experience of the retrieval team was associated with allograft loss (P = .04). In multivariate analysis, donor intensive care unit time ≥5 days (P = .03) and lower experience of the procurement team were associated with increased risk of pancreatic allograft thrombosis (P = .02), whereas recipient's age from 30 to 40 years (P = .018) or ≥40 years (P = .02) was found as a protective factor., Conclusions: Pancreatic allograft thrombosis remains an important cause of graft loss in pancreas transplantation. Recipient's age, prolonged donor intensive care unit time, and lower experience of the procurement team directly influence pancreatic allograft thrombosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted., Material and Methods: The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on., Results: The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship., Conclusion: The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved., Competing Interests: The authors declare that they have no conflicts of interest to declare.

Short bowel syndrome is the most common etiology of intestinal failure, resulting from either resections of different intestinal segments or a congenital condition. Due to the absence or considerable reduction of intestinal loops in the abdominal cavity, patients with short bowel syndrome present with atrophy and muscle retraction of the abdominal wall, which leads to loss of abdominal domain and elasticity. This complication is an aggravating factor of intestinal transplantation since it can prevent the primary closure of the abdominal wall. A vast array of surgical techniques to overcome the challenges of the complexity of the abdominal wall have been described in the literature. The aim of our study was to review the modalities of abdominal wall closure in intestinal/multivisceral transplantation. Our study consisted of a systematic review following the methodological instructions described in the PRISMA guidelines. Duplicate studies and studies that did not meet the criteria for the systematic review were excluded, especially those without relevance and an explicit relationship with the investigated theme. After this step, 63 articles were included in our study. The results obtained with these techniques have been encouraging, but a high incidence of wound complications in some reports has raised concerns. There is no consensus among transplantation centers regarding which technique would be ideal and with higher success rates and lower rates of complications.

Background: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI)., Aim: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI., Methods: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI ., Results: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival., Conclusions: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic., Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were "COVID-19" and "Liver transplantation"., Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5‒44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%., Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The aim of this study was to analyze prognostic indicators of in-hospital mortality among patients listed for urgent liver transplantation (LT) for non-acetaminophen (APAP)-induced acute liver failure (ALF)., Methods: ALF patients listed for LT according to the King's College Criteria were retrospectively reviewed. Variables were recorded from medical records and electronic databases (HCMED and RedCap)., Results: The study included 100 patients, of which 69 were subject to LT and 31 died while waiting for LT. Patients were 35.5 ± 14.73 years old, and 78% were females. The main etiologies were virus (17%), drug-induced (32%), autoimmune (15%), and indeterminate hepatitis (31%). The prioritization-to-LT time interval was 1.5 days (0-9). The non-LT patients showed higher lactate (8.71 ± 5.36 vs. 4.48 ± 3.33 mmol/L), creatinine (229 ± 207 vs. 137 ± 136 µm/L), MELD (44 ± 8 vs. 38 ± 8), and BiLE scores (15.8 ± 5.5 vs. 10.3 ± 4.1) compared to LT patients (p < 0.05). Multiple logistic regression analysis identified creatinine and lactate as independent prognostic factors, and a creatinine-lactate (CL) score was developed. ROC analysis showed that creatinine, lactate, MELD, BiLE, and CL scores had considerable specificity (71-88%), but only BiLE, lactate, and CL presented high sensitivities (70%, 80%, and 87% respectively). AUCs were 0.696 for creatinine, 0.763 for lactate, 0.697 for MELD, 0.814 for BiLE, and 0.835 for CL., Conclusions: CL and BiLE scores predict mortality with more accuracy than MELD in patients with ALF during prioritization time. Creatinine and lactate are independent prognostic factors for mortality.

Background: Liver ischemia reperfusion injury is still an unsolved problem in liver surgery and transplantation. In this setting, hypothermia is the gold standard method for liver preservation for transplantation. Hypertonic saline solution reduces inflammatory response with better hemodynamic recovery in several situations involving ischemia reperfusion injury. Here, we investigated the effect of hypertonic saline solution in hypothermic liver submitted to ischemia reperfusion injury., Methods: Fifty male rats were divided into 5 groups: SHAM, WI (animals submitted to 40 minutes of partial warm liver ischemia and reperfusion), HI (animals submitted to 40 minutes hypothermic ischemia), HSPI (animals submitted to hypothermic ischemia and treated with 7.5% hypertonic saline solution preischemia), and HSPR (animals submitted to hypothermic ischemia and treated with hypertonic saline solution previously to liver reperfusion). Four hours after reperfusion, the animals were euthanized to collect liver and blood samples., Results: Aspartate aminotransferase and alanine aminotransferase, histologic score, and hepatocellular necrosis were significantly decreased in animals submitted to hypothermia compared with the warm ischemia group. Malondialdehyde was significantly decreased in hypothermic groups with a further decrease when hypertonic saline solution was administrated preischemia. Hypothermic groups also showed decreased interleukin-6, interleukin-10, and tumor necrosis factor-α concentrations and better recovery of bicarbonate, base excess, lactate, and glucose blood concentrations. Moreover, hypertonic saline solution preischemia was more effective at controlling serum potassium concentrations., Conclusion: Hypertonic saline solution before hypothermic hepatic ischemia decreases hepatocellular oxidative stress, cytokine concentrations, and promotes better recovery of acid-base disorders secondary to liver ischemia reperfusion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

The impact of coronavirus disease-19 (COVID-19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single-center case series of five consecutive patients in the early postoperative period of deceased-donor liver transplantation who developed nosocomial COVID-19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID-19 diagnosis on 9th postoperative day. The other was 67 years old with non-alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti-thymocyte globulin for treating steroid-resistant rejection. Our novel experience highlights that COVID-19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID-19 nosocomial spread in the early postoperative period., (© 2020 Wiley Periodicals LLC.)

Non-tumoral portal vein thrombosis (PVT) is associated with higher morbidity and mortality in liver transplantation (LT). In this study, we aimed to evaluate the impact of PVT in LT outcomes and analyze the types of surgical techniques used for dealing with PVT during LT. A systematic review was conducted in Cochrane, MEDLINE, and EMBASE databases, selecting articles from January 1990 to December 2019. The MESH-terms used were ("Portal Vein"[Mesh] AND "Thrombosis"[Mesh] NOT "Neoplasms"[Mesh]) AND ("Liver Transplantation"[Mesh]). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendation was used, and meta-analysis was performed with Review Manager Version 5.3 software. A total of 1,638 articles were initially found: 488 in PubMed, 289 in Cochrane Library, and 861 in EMBASE, from which 27 were eventually selected for the meta-analysis. Surgery time of LT in patients with PVT was longer than in patients without LT (p<0.0001). Intraoperative red blood cell (p<0.00001), fresh frozen plasma (p=0.01), and platelets (p=0.03) transfusions during LT were higher in patients with PVT. One-year (odds ratio [OR] 1.17; p=0.002) and 5-year (OR 1.12; p=0.01) patient survival after LT was worse in the PVT group. Total occlusive PVT presented higher mortality (OR 3.70; p=0.00009) and rethrombosis rates (OR 3.47 [1.18-10.21]; p=0.02). PVT Yerdel III/IV classification exhibited worse 1-year [2.04 (1.21-3.42); p=0.007] and 5-year [0.98 (0.59-1.62); p=0.93] patient survival. Thrombectomy with primary anastomosis was associated with better outcomes. LT in patients with non-tumoral PVT demands more surgical time, needs more intraoperative transfusion, and presents worse 1- and 5-year patient survival. Total occlusive PVT and Yerdel III/IV PVT classification were associated with higher mortality. (PROSPERO, registration number: CRD42020132915).

Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were "COVID-19" AND "Transplant." Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299).

Background: Liver transplantation (LT) has evolved to improve graft and patient survival. Early graft dysfunction (EGD) and primary nonfunction are an important cause of morbi-mortality. We had formulated the scientific hypothesis that the liver function can be evaluated by the indocyanine green (IG) after LT. The aim was to evaluate the EGD by plasma disappearance rate (PDR) of IG after LT., Method: Prospective and observational clinical study, from July 2014 to June 2015. IG evaluation by pulse densitometry, Limon system. Degree analysis of ischemia and reperfusion injury in groups as follows: 1 (G0/G1/G2) and 2 (G3/G4). Donor risk index (DRI), Wagener and Olthoff criteria, and prognostic predictors were evaluated. All tests were performed with bidirectional α of 0.05 and a confidence interval of 95% and support by IBM SPSS 25., Results: A total of 40 patients, mean age 53.3 ± 14.0 years and a majority of men and hepatitis C virus. PDR were more relevant with high degrees of ischemia and reperfusion injury grades G3/G4 (P = .030). The PDR related to the donor risk index showed positive significance at DRI >1.5 (P = .066). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death (P = .063)., Conclusion: EGD can be assessed by PDR with high degrees of ischemia and reperfusion injury (G3/G4) and with marginal donors (DRI >1.5). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death of the patient., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Living donor liver transplant (LDLT) is a well-established treatment for end-stage liver disease. A better recipient selection and hemodynamic evaluation may improve transplant outcomes. The aim of this study was to establish recipient parameters that could enhance the results of adult-to-adult LDLT., Methods: We performed a retrospective study of all adult-to-adult LDLTs from a single center between January 2006 and December 2018. Variables analyzed included demographic and clinical parameters, laboratory tests, performance of intraoperative temporary portocaval shunt (TPCS), graft weight/recipient weight ratio (GW/RW), preoperative portal vein thrombosis (PVT), previous major abdominal surgery, and patient survival. Patients were divided in 2 groups according to GW/RW (0.8% cutoff point)., Results: A total of 92 adult-to-adult LDLTs were analyzed, encompassing 53 male patients (57.6%). Mean Model for End-Stage Liver Disease score was 13.97 (SD, 4.74), and 57 patients (61.95%) had Child-Pugh-Turcotte score B. Mean GW/RW was 1.1% (SD, 0.37%). Group 1 with GW/RW > 0.8% (n = 74) and group 2 with it ≤ 0.8% (n = 13) presented mean GW/RW of 1.14% (SD, 0.24%) and 0.69% (SD, 0.09%) and P < .01, respectively. Eighteen patients (19.56%) presented PVT, with a worse survival than those without PVT (P = .006). Sixteen patients (17.39%) with previous major abdominal or biliary operations also presented higher mortality (P = .341). Forty-six (50%) intraoperative TPCSs were performed with a better 1- and 3-year patient survival. Receiver operating characteristic curve analysis showed PVT area under the curve of 0.701 (95% CI, 0.526-0.876; P = .018), positive predictive value of 0.69, and negative predictive value of 0.62. Multivariate analysis showed important risk regarding PVT (odds ratio, 6.160; 95% CI, 1.566-24.223; P = .004) and retransplant (odds ratio, 4.452; 95% CI, 0.843-23.503; P = .06)., Conclusions: Better recipient selection without PVT or previous major abdominal surgery, an adequate GW/RW, and intraoperative TPCS with hemodynamic modulation significantly improve outcomes of adult-to-adult LDLT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Uterine transplantation (UTx) is a surgical therapeutic modality designed for the treatment of patients with exclusive uterine factor infertility. Experimental models are paramount to study this transplant modality, and as the ewes' uteri are very similar to that of humans, they are frequently used with this purpose. The aim of this study is to describe a novel technical variation for UTx in sheep., Methods: This study was conducted at Laboratory of Medical Investigation 37 of the University of São Paulo School of Medicine in São Paulo, Brazil, and was approved by the Ethics Committee of Animal Use of the university. We used 3 adult female sheep that weighed approximately 45 kg and were not pregnant. We performed the technique of uterine autotransplantation with a novel technical variation that we called sequential vascularization: first, we performed the right uterine artery and vein anastomoses, after which the uterine graft was vascularized, and then the contralateral vascular anastomoses were performed., Conclusion: We described 3 successful uterine autotransplants in sheep models with sequential vascularization. This variation technique will probably allow warm ischemia time in UTx to significantly decrease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Currently, the diagnosis of acute on chronic liver failure (ACLF) is clinical, and its early identification and proper management are essential for a better prognosis. The aim of this study was to identify histopathologic parameters by analyzing cirrhotic liver explants that could aid in the early recognition of this entity and to determine prognostic factors that would influence ACLF management., Method: We performed a retrospective analysis of histopathologic material from liver explants from patients transplanted because of chronic hepatitis C virus infection from January 2007 to July 2017. Twenty-nine (n = 29) cases without hepatocellular carcinoma were selected. Histopathologic analysis included the Laennec classification, vascularization, and portal vein thrombosis., Results: According to the diagnosis of ACLF, patients were divided in 2 groups: group ACLF (n = 10) and group no acute on chronic liver failure (NO-ACLF) (n = 19). Considering the whole series, mean age was 51 ± 11.48 years and prevalence of men was 58.62%. The mean Model of End-Stage Liver Disease (MELD) score at time of transplantation was significantly higher in the ACLF group than in the NO-ACLF group (35 ± 7 vs 22 ± 6, respectively, P < .05) as was the mean total bilirubin (14.38 ± 13.31 vs 8.84 ± 10.46 mg/dl, respectively, P < .05). Histopathologic analysis of explanted livers according to Laennec staging system of cirrhosis was as follows: 1. Group NO-ACLF: 1 case (5.25%) grade 3, 6 cases (31.58%) grade 4B, and 12 cases (63.16%) grade 4C; and 2. Group ACLF: 4 cases (40%) grade 4B and 6 cases (60%) grade 4C. Cholestasis was found in 1 patient in the NO-ACLF group (5%) and in 4 patients in the ACLF group (40%) (P = .03). We studied 30-day and 10-year survival respectively, which were 80% and 60% in the ACLF group and 83% and 70% in the NO-ACLF group (P = .794 and P = .657)., Conclusion: In this preliminary approach, clinical and histologic findings contributed to the differential diagnosis of ACLF. The mean MELD score at time of liver transplantations, total bilirubin levels, and histologically evident cholestasis were significantly higher in patients with ACLF than in those without ACLF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Routinely, pediatric donor (PD) grafts are allocated to pediatric liver transplantation (LT) recipients; however, occasionally they can be allocated for adult recipients (ARs). Some authors reported decreased patient/graft survival and higher vascular complications, such as hepatic artery thrombosis (HAT), in LT in ARs using PDs., Methods: It is a retrospective study enrolling 1202 ARs undergoing LT using whole liver grafts during the period of January 2002 to April 2019. The patients were categorized according to donor age in 2 groups: PDs and adult donors (ADs). The variables were collected from the database including the graft to recipient weight ratio (GWRW) and the incidence of HAT and graft primary nonfunction (PNF)., Results: The AD group had 1152 patients, and the PD group had 50 patients. PNF occurred in 68 (5.66%) patients, and the distribution between the 2 groups were similar: 65 (5.64%) in the AD group, and 3 (6%) in the PD group (P = .915). HAT was diagnosed in 30 (2.6%) patients in the AD group and in 6 (12%) patients in the PD group. HAT was significantly higher in the PD group (P = .001). In the PD group, the GWRWs among patients diagnosed with HAT were similar (P = .152)., Conclusion: HAT is higher in PDs, although it is a viable alternative with satisfactory results. Serial Doppler in the first week and early introduction of platelet antiaggregants and/or anticoagulants may be beneficial, albeit it is not clear if it could reduce the incidence of HAT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Transient elastography is a noninvasive method used to estimate the liver stiffness. There are few studies using elastography in acute cellular rejection (ACR). ACR is one of the main complications after liver transplantation. The golden pattern diagnostic is by liver biopsy, which is invasive and subject to complications. Therefore, this paper aims to evaluate the use of elastography in ACR., Methods: Prospective and comparative study of patients transplanted from January 2017 to March 2019. Comparison group (ACR vs non-ACR) through liver biopsy. The variables analyzed were liver elastography (FibroScan and acoustic radiation force impulse [ARFI]), laboratory tests, liver biopsy, and ultrasound. Mann-Whitney U test was used to compare independent samples, and P < .05 was considered significant. All tests performed with α of 0.05 and a confidence interval of 95%, by IBM SPSS 25 software., Results: Forty patients, 25 (62.5%) with ACR and 15 (37.5%) without ACR. Five (20%) cases with early acute rejection, late acute rejection in 19 cases (76%), and chronic rejection in 3 (12%). Comparative ACR vs non-ACR showed results of total bilirubin (P = .03), direct bilirubin (P = .015), aspartate aminotransferase (0.001), alanine aminotransaminase (0.001), and gamma-glutamyl transferase (P = .026). The mean elastography (FibroScan) value in ACR was 12.5 ± 8.2 kPa and without was 8.9 ± 3.7 kPa, P = .05. The mean elastography (ARFI) in ACR was 1.9 ± 0.6 m/s and without was 1.6 ± 0.2 m/s, P > .05. The receiver operator characteristic curve analysis shows the FibroScan for ACR with AUC 0.688 (95% CI 0.511-0.865), P = .049, positive predictive value 0.76, and negative predictive value 0.60., Conclusions: Transient elastography is an important tool for ACR. There is a significant correlation between ACR and the value of hepatic elastography., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Size mismatch between donor and recipients may negatively influence postoperative results of liver transplantation (LT). In deceased donor LT for adults, large grafts are occasionally rejected due to the fear of primary nonfunction. The aim of this study is to assess the feasibility of using large liver grafts in adults undergoing deceased donor LT., Methods: We performed a retrospective study including adult patients who underwent deceased donor LT at our center between January 2006 and September 2019. Recipients with donors aged less than 18 years and those receiving split-liver grafts were excluded. Graft weight of 1800 grams was the cutoff used to divide patients in 2 groups: group 1 (graft weighing < 1800 g) and group 2 (grafts weighing ≥ 1800 g)., Results: A total of 806 patients were included in the study. group 1 and 2 included 722 and 84 recipients, respectively. A larger proportion of male recipients was obseved in group 2: 64.8% vs 76.2% (P = .0037). Mean graft weight in group 1 and 2 was, respectively, 1348 ± 231.81 g and 1986.57 ± 165.51 g (P < .001), which resulted in significantly higher graft weight/recipient weight ratio and graft weight/standard liver volume ratio in group 2. In group 2, there were 9 (10.71%) patients with portal vein thrombosis as well as 24 patients (28.5%) with bulky ascites and 44 grafts (52.3%) with steatosis. Primary closure of the abdominal wall was not possible in 5 patients (5.9%) from this group. Primary nonfunction was diagnosed in 14 cases (16.6%), with liver retransplantation being performed in 6 of them. Male to female sex combination occurred in 19% of LT in group 2., Conclusion: The use of large grafts is feasible; however, proper matching between donor and recipient is paramount, especially taking into consideration graft steatosis, portal vein thrombosis and the presence of bulky ascites., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Intraoperative temporary portocaval shunt (TPCS) has been performed during liver transplant to improve hemodynamics and renal function as well as to decrease bleeding during hepatectomy. The aim of this study was to evaluate the impact of TPCS on liver transplant in a long-term single-center study., Methods: From January 2006 to December 2018, all deceased donor transplants were retrospectively evaluated. Patients were divided in 2 groups: group 1, including those in whom intraoperative TPCS was performed and group 2, including those without TPCS. We analyzed recipient characteristics, survival, mortality, and complication rates in the intraoperative and postoperative periods., Results: A total of 999 deceased donor liver transplants were studied, with 509 patients in group 1 and 490 in group 2. There were 156 cases (15.61%) of preoperative portal vein thrombosis in the whole series. Postoperative renal function (P = .029) as well as length of hospital and intensive care unit stay (P = .0001) were better in group 1. Surgery time and warm ischemia time was also shorter in group 1 (P = .0001). Complications with Clavien-Dindo score ≥ 3 were higher in group 2 (P = .006). Multivariate analysis showed important risk with fulminant hepatitis (odds ratio, 2.127; 95% CI, 1.408-3.213; P < .0001) and Model for End-Stage Liver Disease > 29 (odds ratio, 2.492; 95% CI, 1.862-3.336; P < .0001). Overall survival in group 1 at 1, 5, and 10 years were 78%, 70%, and 68%, respectively. In group 2, they were 70%, 60%, and 58%, respectively (P = .027)., Conclusions: Patients who underwent intraoperative TPCS presented better postoperative renal function, less intraoperative blending, shorter surgical and warm ischemia time, shorter length of hospital and intensive care unit stay, and better overall survival after transplant. Moreover, TPCS should be used patients with severe conditions, such as fulminant hepatitis and Model for End-Stage Liver Disease score > 29., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Surgical treatment of abdominal hernias in cirrhotics is often delayed due to the higher morbidity and mortality associated with the underlying liver disease. Some patients are followed conservatively and only operated on when complications occur ("wait and see" approach). The aim of this study is to compare outcomes of cirrhotic patients undergoing conservative non-operative care or elective hernia repair., Methods: A prospective observational study including 246 cirrhotic patients with abdominal hernia was carried out. Patients were given the option to select their treatment: elective hernia repair or conservative non-operative care. Demographics, characteristics of underlying liver disease, type of hernia, complications and mortality were analyzed. During follow-up of patients who opted for the "wait and see" approach, emergency hernia repair was performed in case of hernia complications., Results: Elective hernia repair was performed in 57 patients and 189 patients were kept in conservative care, of which 43 (22.7%) developed complications that required emergency hernia repair. Elective surgery provided better five-years survival than conservative care (80% vs. 62%; p = 0.012). Multivariate analysis identified multiples hernias [Hazards Ratio (HR):6.7, p < 0.001] and clinical follow-up group (HR 3.62, p = 0.005) as risk factors for mortality. Among patients undergoing surgical treatment, multivariate analysis revealed MELD>11 (HR 7.8; p = 0.011) and emergency hernia repair (HR 5.35; p = 0.005) as independent risk factors for 30-day mortality., Conclusions: Elective hernia repair offers an acceptable morbidity and ensures longer survival. "Wait and see" approach jeopardizes cirrhotic patients and should be avoided, given the higher incidence of emergency surgery due to hernia complications., Competing Interests: All authors declare no conflict of interest related to this study., (© 2019 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Translational medicine has become a priority, but there is still a big difference between the arrival of new treatments and investment. Basic science should not be neglected because the translation from basic research is not sustained in the absence of basic research. The purpose of this literature review was to analyze the translational medicine in the liver transplant field: liver ischemia-reperfusion injury (IRI), immunosuppression, clinical and surgical complications, small-for-size syndrome (SFSS), rejection, and ongoing innovations (liver machine, liver preservation, artificial livers, and regenerative medicine). We performed a systematic literature review that were updated in October 2016. The searches were performed in the Cochrane Central Register of Controlled Trials and Review, PubMed/Medline, Embase, and LILACS databases. All the selected studies on the management of translational medical research in liver transplantation (LT) were analyzed. Initially the search found 773 articles. Methodological viewing and analysis of the articles, followed by the application of scientific models, including translational medicine in the liver transplant field. In conclusions, this review demonstrates the application of scientific research with translation medical benefits regarding the LT. The literature has a great tendency, improvements and investments in the study of translational medicine in LT. Innovative studies and technologies from basic science help to clarify clinical doubts. Moreover, evidence increases the importance of scientific research in quality of clinical practice care., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

BACKGROUND Expanded clinical and surgical techniques in liver transplantation can markedly improve patient and graft survival. The main purpose of this study was to evaluate the efficacy of intraoperative portocaval shunts in liver transplantation. MATERIAL AND METHODS Searches were conducted in Cochrane, MEDLINE, and EMBASE databases, and updated in January 2018. The following specific outcomes of interest were defined and evaluated separated using 2 different reviews and meta-analyses for 1) hemi-portocaval shunt (HPCS) and 2) temporary portocaval shunt (TPCS). Comparative studies were analyzed separately for both surgical portocaval shunt modalities. RESULTS Only 1 well-designed randomized controlled trial was found. Most studies were retrospective or prospective. Initially, we found 1479 articles. Of those selected, 853 were from PubMed/MEDLINE, 32 were from Cochrane and 594 were from EMBASE. Our meta-analysis included a total of 3232 patients for all the included studies. Results found that 41 patients with HPCS experienced increased 1-year patient survival (OR 16.33; P=0.02) and increased 1-year graft survival (OR 17.67; P=0.01). The TPCS analysis with 1633 patients found patients had significantly shorter intensive care unit length of stay (days) (P=0.006) and hospital length of stay (P=0.02) and had decreased primary nonfunction (PNF) (OR 0.30, P=0.02) and mortality rates (OR 0.52, P=0.01). CONCLUSIONS Intraoperative surgical portosystemic shunt in relation to liver transplantation with TPCS was able to prevent PNF, decrease hospital length of stay and unit care length of stay. Furthermore, in analyzing data for patients with HPCS, we observed increases in the 1-year graft and patient survival rates. More prospective randomized trials are needed to arrive at a more precise conclusion.

Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent primary liver neoplasm after hepatocellular carcinoma (HCC), corresponding to 10% to 15% of cases. Pathologies that cause chronic biliary inflammation and bile stasis are known predisposing factors for development of ICC. The incidence and cancer-related mortality of ICC is increasing worldwide. Most patients remain asymptomatic until advance stage, commonly presenting with a liver mass incidentally diagnosed. The only potentially curative treatment available for ICC is surgical resection. The prognosis is dismal for unresectable cases. The principle of the surgical approach is a margin negative hepatic resection with preservation of adequate liver remnant. Regional lymphadenectomy is recommended at time of hepatectomy due to the massive impact on outcomes caused by lymph node (LN) metastasis. Multicentric disease, tumor size, margin status and tumor differentiation are also important prognostic factors. Staging laparoscopy is warranted in high-risk patients to avoid unnecessary laparotomy. Exceedingly complex surgical procedures, such as major vascular, extrahepatic bile ducts and visceral resections, ex vivo hepatectomy and autotransplantation, should be implemented in properly selected patients to achieve negative margins. Neoadjuvant therapy may be used in initially unresectable lesions in order to downstage and allow resection. Despite optimal surgical management, recurrence is frustratingly high. Adjuvant chemotherapy with radiation associated with locoregional treatments should be considered in cases with unfavorable prognostic factors. Selected patients may undergo re-resection of tumor recurrence. Despite the historically poor outcomes of liver transplantation for ICC, highly selected patients with unresectable disease, especially those with adequate response to neoadjuvant therapy, may be offered transplant. In this article, we reviewed the current literature in order to highlight the most recent advances and recommendations for the surgical treatment of this aggressive malignancy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Liver elastography have been reported in hepatocellular carcinoma (HCC) with higher values; however, it is unclear to identify morbimortality risk on liver transplantation waiting list., Aim: To assess liver stiffness, ultrasound and clinical findings in cirrhotic patients with and without HCC on screening for liver transplant and compare the morbimortality risk with elastography and MELD score., Method: Patients with cirrhosis and HCC on screening for liver transplant were enrolled with clinical, radiological and laboratory assessments, and transient elastography., Results: 103 patients were included (without HCC n=58 (66%); HCC n=45 (44%). The mean MELD score was 14.7±6.4, the portal hypertension present on 83.9% and the mean transient elastography value was 32.73±22.5 kPa. The median acoustic radiation force impulse value of liver parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC group was significantly associated with HCV infection (OR 26.84; p<0.0001), higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under the receiver operating characteristics (AUROC) showed sensitivity and specificity for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value (cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value 2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival group had a mean transient elastography value of 31.65±22.2 kPa vs. 50.87±20.9 kPa (p=0.098) and higher MELD scores (p=0.035)., Conclusion: Elastography, ultrasound and clinical findings are important non-invasive tools for cirrhosis and HCC on screening for liver transplant. Higher values in liver elastography and MELD scores predict mortality.

Background: Transient elastography (TE) is a noninvasive technique that measures liver stiffness. When an inflammatory process is present, this is shown by elevated levels of stiffness. Acute cellular rejection (ACR) is a consequence of an inflammatory response directed at endothelial and bile epithelial cells, and it is diagnosed through liver biopsy. This is a systematic review of the viability of TE in ACR following liver transplantation., Methods: The Cochrane Library, Embase, and Medline PubMed databases were searched and updated to November 2016. The MESH terms used were "Liver Transplantation," "Graft Rejection," "Elasticity Imaging Techniques" (PubMed), and "Elastography" (Cochrane and Embase)., Results: Seventy studies were retrieved and selected using the PICO (patient, intervention, comparison or control, outcome) criteria. Three prospective studies were selected to meta-analysis and evaluation. A total of 33 patients with ACR were assessed with TE. One study showed a cutoff point of >7.9 kPa to define graft damage and <5.3 kPa to exclude graft damage (receiver operating characteristic 0.93; P < .001). Another study showed elevated levels of liver stiffness in ACR patients. However, in this study, no cutoff point for ACR was suggested. The final prospective study included 27 patients with ACR at liver biopsy. Cutoff points were defined as TE > 8.5 kPa, moderate to severe ACR, with a specificity of 100% and receiver operating characteristic curve of 0.924. The measurement of TE < 4.2 kPa excludes the possibility of any ACR (P = .02)., Conclusions: TE may be an important tool for the severity of ACR in patients following liver transplantation. Further studies should be performed to better define the cutoff points and applicability of the exam., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the Model for End-Stage Liver Disease (MELD) system, patients with "MELD exceptions" points may have unfair privilege in the competition for liver grafts. Furthermore, organ distribution following identical ABO blood types may also result in unjust organ allocation. The aim of this study was to investigate access to liver transplantation in a tertiary Brazilian center, regarding "MELD exceptions" situations and among ABO-blood groups., Methods: A total of 465 adult patients on the liver waitlist from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to ABO-blood type and presence of "exceptions points.", Results: No differences in outcomes were observed among ABO-blood groups. However, patients from B and AB blood types spent less time on the list than patients from A and O groups (median, 46, 176, 415, and 401 days, respectively; P = .03). "Exceptions points" were granted for 141 patients (30.1%), hepatocellular carcinoma being the most common reason (52.4%). Patients with "exceptions points" showed higher transplantation rate, lower mortality on the list, and lower delta-MELD than non-exceptions patients (56.7% vs 19.1% [P < .01]; 18.4% vs 38.5% [P < .01], and 2.0 ± 2.6 vs 6.9 ± 7.0 [P < .01], respectively). Patients with refractory ascites had a higher mortality rate than those with other "exceptions" or without (48%)., Conclusions: The MELD system provides equal access to liver transplantation among ABO-blood types, despite shorter time on the waitlist for AB and B groups. The current MELD exception system provides advantages for candidates with "exception points," resulting in superior outcomes compared with those without exceptions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Liver transplantation has evolved significantly in recent years, with each advancement part of the effort toward increasing patient and graft survival as well as quality of life. The objective of this study was to evaluate the prognostic factors and selection criteria for liver transplantation., Methods: Our study was a statistical analysis, logistic regression, and survival evaluation of a total of 80 liver transplants that were performed between June 1, 2016 and September 24, 2016. Recipient factors evaluated included age, retransplantation, hemodialysis, cardiac risk, portal vein thrombosis, hospitalization, fulminant hepatitis, previous surgery, renal failure, and Model for End-stage Liver Disease (MELD) score. Donor factors included age, cardiac arrest, acidosis, days in the intensive care unit, steatosis, and vasoactive drug use., Results: Of the 80 patients transplanted, 65 deceased donor liver transplants (DDLTs) and 15 living donor liver transplants (LDLTs) were performed. LDLT overall 1-year patient survival was 77.5% and graft survival 75%, and DDLT overall patient survival was 89.23% and graft survival was 86.15%. On evaluated score criteria analyzed we observed a significant score on recipient (P = .01) and not significant on donor (P =.45). Isolated factors evaluated included recipient age (relative risk [RR] 3.15, 95% confidence interval [CI] 0.89 to 11.09; P = .074), retransplant (RR 4.22, 95% CI 1.36 to 13.1; P = .013), and hemodialysis (RR 4.23, 95% CI 1.45 to 12.31, P = .008). On donor evaluation, we observed moderate and severe steatosis (RR 3.8, 95% CI 0.86 to 16.62; P = .06)., Conclusion: In conclusion, we demonstrate a relevant model of criteria selection of liver transplant patients that is able to make a better match between the donor and recipient allocation for a better graft and patient survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)