Safety Of Liver Transplantation Research Articles

Liver transplantation consideration and evaluation: a life-saving treatment in acute-on-chronic liver failure

With the rising prevalence of chronic liver disease worldwide, the incidence and prevalence of acute-on-chronic liver failure (ACLF) are increasing and attribute to higher morbidity, mortality, and healthcare costs. Many of such patients die without being considered for the lifesaving treatment option of liver transplantation. The underutilization of liver transplantation as a therapeutic option in the setting of ACLF, is due to multiple reasons; with the heterogeneity of ACLF and the lack of universal definition being the key players. Liver transplantation listing and allocation are based on MELD score. As of now, we do not know where MELD score stands in regard to defining ACLF and the prognostication of such patients. This insight is very important for the efficient identification of potential liver transplantation candidates in the setting of ACLF. This review paper investigates the role of liver transplantation in the setting of ACLF. In light of recent evidence, MELD score is not the perfect model in the setting of ACLF either. The safety of liver transplantation, either deceased donor or living donor, among ACLF patients has been debated. The short-term mortality rate of ACLF patients has created a need for a standard liver transplant selection criterion for these patients. Based on published literature, we find that three commonly used ACLF definitions may be used in combination to define the sensitivity, specificity, and futility of ACLF and we propose an algorithm to best identify patients for urgent liver transplantation in the setting of ACLF. Moreover, we discuss the data on the safety of liver transplantation in the setting of ACLF. Future validation of this multifaceted approach could bridge the gap between ACLF patients and appropriately guided medical intervention.

Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial)

BackgroundPatients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. Patients and MethodsThe COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). ResultsPrimary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). ConclusionLT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Liver Transplantation Using Allografts With Recent Liver Blunt Trauma: A Nationwide Audit From the French CRISTAL Biomedicine Agency Registry.

In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking. All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint. Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels ( P < 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system ( P < 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively. Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.

Liver transplantation as a treatment for Wilson\u2019s disease with neurological presentation: a systematic literature review

IntroductionWilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. However, in almost 50% of WD patients, neurological symptoms persist despite treatment, and in up to 10% of patients, neurological deterioration is irreversible. International guidelines on WD treatment do not recommend liver transplantation (LT) as a treatment for neurological symptoms in WD. However, such treatment has been assessed in retrospective analyses, case and series reports. We aimed to systematically assess all available evidence on the effectiveness and safety of LT in WD patients with neurological presentation.MethodsThis systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 6 April 2021) and by screening reference lists.ResultsBased on the systematic literature review, 48 articles were identified, showing outcomes of LT in 302 WD patients with neurological symptoms. Of these patients, major improvement was found in 215 cases (71.2%), with no difference in neurological status before and after LT in 21 cases (6.9%). There were 29 deaths (9.6%), neurological worsening in 24 cases (7.9%), and 13 cases (4.3%) were lost to follow-up.ConclusionsThe results suggest that LT is a promising method of WD management in patients with severe, neurological symptoms, particularly if the patient has not responded to pharmacological de-coppering treatment. Further studies of LT in these patients are warranted.

Orthotopic Liver Transplantation Using Allografts from Donors with Recent Liver Trauma Injury: A Nationwide Snapshot from the French Cristal Biomedecine Agency Registry

Introduction: In the current setting of organ shortage, brain dead liver donors with recent liver injury (RLI) represents a potential pool of donors. Yet, data on safety of liver transplantation (LT) using grafts with RLI are lacking. Methods: All liver grafts from brain-dead donors with RLI proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating both feasibility and safety of LT with 1-year survival as the primary endpoint. Results: Among 11073 LT, 142 (1.2%) using grafts with RLI were performed. These 142 LT including 23 split LT were performed from 131 donors (46.1%) out of 284 donors with RLI proposed for LT. Transplanted grafts were procured from donors with significantly lower liver enzymes levels (p<0.001) and less advanced liver trauma according to the AAST liver grading system (p=0.013) as compared to not transplanted grafts. Before allocation, 19 (6.7%) out of 284 donors underwent damage control intervention. During transplantation, surgical management directed to the liver was reported in 19 patients (13%), consisting in local hemostatic control (n=15), partial hepatic resection (n=3) or perihepatic packing (n=1). Ninety-day mortality and severe morbidity rates were 8.5% (n=12) and 29% (n=42), respectively. One-year OS and GS rates were 85% and 84%. Five-year OS and GS rates were respectively of 77% and 74%. Conclusion: Using grafts from donors with RLI appears safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma including liver injury should be considered for organ allocation.

S2739 Successful Use of Plasmapheresis in Concurrent Fulminant Acute Fatty Liver of Pregnancy and COVID-19 Infection

Introduction: Acute fatty liver of pregnancy (AFLP) is a rare condition characterized by maternal liver dysfunction and/or failure during the third trimester or early postpartum period, thought to be caused by defects in fatty acid metabolism during pregnancy. Management includes prompt delivery and supportive care. In the following case, we describe a patient found to have fulminant liver failure after delivery but was unable to undergo liver transplantation due to Coronavirus Disease 2019 (COVID-19) infection. Fortunately, with plasmapheresis, the patient recovered from both fulminant liver failure and COVID-19. Case Description/Methods: A 26-year-old female 38 weeks pregnant with recent diagnosis of COVID-19 infection presented with 3 days of nausea, vomiting, abdominal pain, and polydipsia. Due to non-reassuring fetal heart rate tracings, emergency cesarean section was performed. On post-partum day one, she was noted to be somnolent and jaundiced. Laboratory testing revealed a leukocytosis of 17,800, platelets 168,000, creatinine 3.95 mg/dL, glucose 26 mg/dL, uric acid 8.4 mg/dL, total bilirubin 8.5 mg/dL, AST 234 U/L, ALT 224 U/L, ALP 466 U/L, PT 57.3 s, and ammonia 69 µmol/L. A chest x-ray showed bibasilar opacities; abdominal ultrasound revealed a mildly fatty liver and ascites. Viral, autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson’s serologies were unremarkable. Thirteen Swansea criteria were met, thus a diagnosis of AFLP was made. Liver transplantation was initially considered but was high risk due to active COVID-19 infection resulting in respiratory failure requiring intubation. After multidisciplinary discussion, she was started on plasmapheresis. After 6 days of plasmapheresis, liver and renal function improved. She was discharged home on post-partum day 19. Discussion: In the above case, we describe a patient with COVID-19 infection with fulminant liver failure from AFLP. The patient needed a liver transplant due to rapidly worsening liver function. However, due to limited data on the safety of liver transplantation in active COVID-19 infection, it was deemed high-risk. Fortunately, the patient’s condition improved with plasmapheresis, and liver transplant was not needed. Plasmapheresis removes toxins, ammonia, and inflammatory cytokines while replacing coagulation factors, albumin, and biologically active substances that are typically produced by liver cells. The therapy has also been reported to be an effective salvage treatment for severe cases of COVID-19.

Safe surgery checklist: content validation proposal for liver transplantation.

to develop the safe surgery checklist for liver transplantation according to the original model of the World Health Organization and perform content validation. a methodological research developed in four stages: integrative review; expert participation; consensus among researchers; and content validation using the Delphi technique in two rounds, by five judges. For data analysis, the Content Validation Index was used. the first version of the checklist consisted of four surgical moments with 64 items of verification, with an average Content Validation Index of 0.80. After adjustments, in the second round the checklist maintained four surgical moments with 76 items and a Content Validation Index of 0.87. the checklist was validated and adequate for the safety of liver transplantation in the surgical environment, given that each item established must be mapped and managed for the success and effectiveness of the procedure.

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma

BackgroundThe benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC. MethodsPatients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE. ResultsAmong 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p < 0.001), an efficient downsizing (p < 0.001) as well as a significant downstaging based on BCLC classification (p < 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively. DiscussionLiver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC.

Efficacy and safety of liver transplantation in patients with cholangiocarcinoma: A systematic review and meta‐analysis

The aim of our study was to evaluate the efficacy and safety of liver transplantation in patients with cholangiocarcinoma. According to the requirements of Cochrane systematic review, a thorough literature search was performed in PubMed/Medline, Embase and Cochrane electronic databases between 1995 and 2009 in terms of the key words "liver transplantation" and "cholangiocarcinoma," "cholangiocellular carcinoma" or "bile duct cancer," with restricted articles for the English language. Data were processed for a meta-analysis by Stata 10 software. Altogether 14 clinical trials containing 605 transplanted patients of bile duct cancers were finally enrolled in our study. The overall 1-, 3- and 5-year pooled survival rates were 0.73 [95% confidence interval (CI) = 0.65-0.80], 0.42 (95% CI = 0.33-0.51) and 0.39 (95% CI = 0.28-0.51), respectively. Of note, preoperative adjuvant therapies [orthotopic liver transplantation (OLT)-PAT group] rendered the transplanted individuals with comparably favorable outcomes with 1-, 3- and 5-year pooled survival rates of 0.83 (95% CI = 0.57-0.98), 0.57 (95% CI = 0.18-0.92) and 0.65 (95% CI = 0.40-0.87). In addition, the overall pooled incidence of complications was 0.62 (95% CI = 0.44-0.78), among which that of OLT-PAT group (0.58; 95% CI = 0.20-0.92) was relatively acceptable compared to those of liver transplantation alone (0.61; 95% CI = 0.33-0.85) and liver transplantation with extended bile duct resection (0.78; 95% CI = 0.55-0.94). In comparison to curative resection of cholangiocarcinoma with the 5-year survival rate reported from 20 to 40%, the role of liver transplantation alone is so limited. In the future, attention will be focused on liver transplantation following neoadjuvant radiochemotherapy, which requires a well-designed, prospective randomized controlled study.

Safety of liver transplantation with chagas disease-seropositive donors for seronegative recipients

The shortage of organs for transplantation has prompted the investigation of extended criteria donors, such as donors with transmissible infectious diseases. Here we report our recent experience with liver transplantation using organs from donors who were serologically positive for Chagas disease. We also provide a review of the literature and emphasize donor screening and preventive measures.

Liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma

Sorafenib is a multikinase inhibitor currently used in the palliative treatment of advanced hepatocellular carcinoma. In patients with small hepatocellular carcinoma, sorafenib could be suggested as neoadjuvant therapy to control tumor growth during waiting time for liver transplantation. However, up to now, safety of liver transplantation in patients undergoing sorafenib treatment is not known. Herein, we report a case of successful liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma. In this patient, liver transplantation was performed safely and histological examination of explanted liver evidenced complete necrosis of the largest tumor nodule.

Split liver transplantation: two grafts from one donor is the optimal use of a scarce resource

T he effort of establishing the efficacy and safety of liver transplantation has been a victim of its own success now that there are insufficient numbers of donor organs available for grafting. Some expansion of the donor pool has been brought about by the use of living donors, first successfully performed in Brisbane,’ extensively developed by Broelsch et al,29 and vigorously deployed in Japan4 Although there are reports now appearing of its use in adult transplantationP6 it is principally a technique for paediatric recipients. 4,7 A hugely increased donor pool will be realised if xenotransplantation becomes clinically viable, but this is unlikely to happen before the next millenium. Some of the forrnidable problems related to hyperacute rejection are now being successfully addressed, but the issue of potential zoonotic infection reminds us that the use of animal donors is complex and not yet so1ved.s The report of viable sheep derived from adult mammary epithelial cells9 raises the spectre of generating genetically modified organs to order, but this is even further from the clinical arena for both scientific and moral reasons.‘O In this review, the contribution of a technical strategy to donor shortage is considered. Split liver grafting, in which a donor liver is divided into two grafts, was first reported in 1988” and since that time has evolved from its use in urgent cases to the elective situation. In the next section, stages in the development of split grafting are discussed. Subsequent sections address logistical and practical details, anatomical constraints and considerations, reported results from centres worldwide and from our own program, and an appraisal of the strategy on transplant numbers.