COVID-19 Pandemic Impact on Liver Donation in the Largest Brazilian Transplantation Center.

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.

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).

Prognostic Factors Evaluation for Liver Transplant Mismatching: A New Way of Selecting and Allocating Organs.

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.

Duodenal Necrosis and Nonvariceal Digestive Bleeding After Terlipressin Administration for Treatment of Hepatorenal Syndrome: a Case Report of a Novel Side Effect of a Commonly Used Drug.

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.

Relationship of Anatomic Variations and Arterial Reconstruction of the Hepatic Artery: Prevalence and Effect on Orthotopic Liver Transplantation.

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.

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.

Hepatic Venous Outflow Obstruction in Adult Deceased Donor Liver Transplantation: Classic Piggyback Implantation Versus a Modified Technique that Widens the Ostium of the Recipient's Left and Middle Hepatic Veins.

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.

Septuagenarian Donors and Recipients in Deceased Donor Liver Transplantation: A Brazilian Single Center Experience and Literature Review.

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.

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model.

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.

Innovative Technique Avoiding Bleeding After Reperfusion in Living Donor Liver Transplant Using a Modified Right Lobe Graft.

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.

Incidence of Donor Hepatic Artery Thrombosis in Liver Grafts Recognized During Organ Procurement and Backtable: A Rare but Treacherous Pitfall In Liver Transplantation.

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/m2, 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.

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)

Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy: A case report and review of literature.

BACKGROUND: Primary extra-gastrointestinal stromal tumors (E-GIST) of the liver are rare. The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect. Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care. However, under specific circumstances, a cytoreductive approach may represent a therapeutic option. We describe herein the case of an 84-year-old woman who presented with a tender, protruding epigastric mass. Abdominal computed tomography scan revealed a large, heterogeneous mass located across segments III, IV, V, and VIII of the liver. The initial approach was transarterial embolization of the tumor, which elicited no appreciable response. Considering the large size and central location of the tumor and the advanced age of the patient, non-anatomic complete resection was indicated. Due to substantial intraoperative bleeding and hemodynamic instability, only a near-complete resection could be achieved. Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver. Considering the risk/benefit ratio for therapeutic options, debulking surgery may represent a strategy to control pain and prolong survival. CASE SUMMARY: Here, we present a case report of a patient diagnosed with E-GIST primary of the liver, which was indicated a cytoreductive surgery and adjuvant therapy with imatinib. CONCLUSION: E-GIST primary of the liver is a rare conditional, the treatment is with systemic therapy and total resection surgery. However, a cytoreductive surgery will be necessary when a complete resection is no possible.