Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model.

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.

Liver Transplantation for Benign Massive Hepatomegaly: Results From a Single Center and Contribution of the Left-to-Right Piggyback Approach.

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.

Retransplantation for Late Hepatic Artery Thrombosis: Results from a Single Center.

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.

Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model

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.

Multivisceral transplantation of pelvic organs in rats.

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%.

Clinical Validation of a Novel Scoring System Based on Donor and Recipient Risk Factors for Predicting Outcomes in Liver Transplantation.

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.

Liver transplant after SARS-CoV-2 infection: A systematic review.

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).

Experimental Clinical Model of Liver Transplantation in Large White Pigs Without Venovenous Bypass: Pre-, Intra-, and Maintenance Care.

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.

Techniques for Closing the Abdominal Wall in Intestinal and Multivisceral Transplantation: A Systematic Review.

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.

CIRRHOTIC PATIENTS WITH ACUTE KIDNEY INJURY (AKI) HAVE HIGHER MORTALITY AFTER ABDOMINAL HERNIA SURGERY.

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.

Liver transplant after SARS-CoV-2 infection: A systematic review

Abstract 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)

Hypertonic saline solution decreases oxidative stress in liver hypothermic ischemia.

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.

Living-donor liver transplantation in Budd-Chiari syndrome with inferior vena cava complete thrombosis: A case report and review of the literature.

BACKGROUND: Budd-Chiari syndrome (BCS) is a challenging indication for liver transplantation (LT) due to a combination of massive liver, increased bleeding, retroperitoneal fibrosis and frequently presents with stenosis of the inferior vena cava (IVC). Occasionally, it may be totally thrombosed, increasing the complexity of the procedure, as it should also be resected. The challenge is even greater when performing living-donor LT as the graft does not contain the retrohepatic IVC; thus, it may be necessary to reconstruct it. CASE SUMMARY: A 35-year-old male patient with liver cirrhosis due to BCS and hepatocellular carcinoma beyond the Milan criteria underwent living-donor LT with IVC reconstruction. It was necessary to remove the IVC as its retrohepatic portion was completely thrombosed, up to almost the right atrium. A right-lobe graft was retrieved from his sister, with outflow reconstruction including the right hepatic vein and the branches of segment V and VIII to the middle hepatic vein. Owing to massive subcutaneous collaterals in the abdominal wall, venovenous bypass was implemented before incising the skin. The right atrium was reached via a transdiaphragramatic approach. Hepatectomy was performed en bloc with the retrohepatic vena cava. It was reconstructed with an infra-hepatic vena cava graft obtained from a deceased donor. The patient remains well on outpatient clinic follow-up 25 mo after the procedure, under an anticoagulation protocol with warfarin. CONCLUSION: Living-donor LT in BCS with IVC thrombosis is feasible using a meticulous surgical technique and tailored strategies.

Portal vein surgical treatment on non-tumoral portal vein thrombosis in liver transplantation: Systematic Review and Meta-Analysis.

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).

Portal vein surgical treatment on non-tumoral portal vein thrombosis in liver transplantation: Systematic Review and Meta-Analysis

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).

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

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.

Cirrhotic patients with acute kidney injury (aki) have higher mortality after abdominal hernia surgery / Pacientes cirróticos com lesão renal aguda tem maior mortalidade após cirurgia de hérnia abdominal

ABSTRACT 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.

RESUMO Racional: A incidência de hérnia abdominal em pacientes cirróticos é elevada, em torno de 20%. Em casos de ascite volumosa, a incidência atinge valores até 40%. Uma das principais e mais graves complicações no pós-operatório de correção de hérnias de pacientes cirróticos é a insuficiência renal aguda (IRA). Objetivo: Analisar a função renal de pacientes cirróticos submetidos a herniorrafias, comparando aqueles que apresentavam IRA pós-operatório com os demais, para determinar os fatores relacionados à sua ocorrência. Método: Seguimento de pacientes cirróticos submetidos à cirurgia de hérnia entre 2001 e 2014 no Serviço de Transplante de Fígado. Foram coletados exames laboratoriais para avaliar a função renal no pós-operatório rotineiramente. A IRA foi definida com base no consenso do clube da ascite em 2015. Resultados: Dos 174 pacientes incluídos, ocorreu IRA em 58 pacientes (34,9%). Houve diferença entre grupos para as seguintes variáveis: MELD inicial, creatinina basal e creatinina, o grupo com IRA apresentou medias superiores ao grupo que não apresentou IRA. No grupo IRA PO, 74,1% das cirurgias, foram realizadas em caráter de emergência, enquanto que no grupo sem IRA no pós-operatório, 34,6%. No grupo IRA, 90,4% dos indivíduos apresentaram complicações no pós-operatório, enquanto no grupo sem IRA, 29,9%. As variáveis idade, MELD inicial, creatinina basal e creatinina no pós-operatório inicial foram estatisticamente significantes na análise de sobrevida. Conclusões: Existe uma associação entre IRA pós-operatória e cirurgia de emergência e IRA pós-operatóri e complicações pós-operatórias. Os fatores relacionados à maior ocorrência de IRA em pacientes cirróticos submetidos à cirurgia de hérnia são o MELD inicial, creatinina basal, creatinina pós-operatória inicial. O preparo de pacientes cirróticos com hérnia abdominal antes de procedimentos cirúrgicos deve ocorrer sistematicamente, pois apresentam alta incidência de IRA pós-operatória.

Histopathologic Evaluation of Acute on Chronic Liver Failure.

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.

Adult-to-Adult Living Donor Liver Transplant: Hemodynamic Evaluation, Prognosis, and Recipient Selection.

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.