History Of Liver Transplantation Research Articles

Daño renal asociado al trasplante hepático

IntroductionKidney injury associated with paediatric liver transplantation (LT) is common, but its evaluation is challenging. Our aim was to analyse the presence of perioperative acute kidney injury (AKI) and study the prevalence of chronic kidney disease (CKD) using different glomerular filtration rate (GFR) estimation formulas. MethodsWe conducted a cross-sectional study in a cohort of children aged less than 18years with a history of LT followed up for 5.42years. We estimated the GFR using the creatinine-based Schwartz bedside formula (2009), the cystatin C-based Caucasian Asian Pediatric and Adult cohort (CAPA) equation and the combined full-age spectrum (FAS) formula as modified by Pottel. We analysed the agreement between them using the Bland-Altman method and the kappa statistic. We measured the albumin level in urine, the urine volume adjusted to 100mL of GFR and blood pressure. We performed univariate and multivariate analyses of the risk factors associated with CKD. ResultsThe sample included 52 patients with a median age of 9.21years. Fifteen (28.8%) had AKI. Five (10%) had CKD and the only associated risk factor was acute liver failure at the time of LT (odds ratio, 8.57; P=.04). There was poor agreement between the different estimation formulas. One patient was classified as having CKD with the Schwartz formula compared to four patients with the CAPA and the Pottel combined FAS formulas. Up to 42% of children without CKD had some positive marker of kidney injury. ConclusionsThe exclusive use of the 2009 Schwartz bedside formula to estimate GFR may lead to underdiagnosis of CKD in children post LT. Other markers of kidney injury are common, and their detection may help prevent the progression of CKD.

Kidney injury associated with liver transplantation

IntroductionKidney injury associated with paediatric liver transplantation (LT) is common, but its evaluation is challenging. Our aim was to analyse the presence of perioperative acute kidney injury (AKI) and study the prevalence of chronic kidney disease (CKD) using different glomerular filtration rate (GFR) estimation formulas. MethodsWe conducted a cross-sectional study in a cohort of children aged less than 18 years with a history of LT followed up for 5.42 years. We estimated the GFR using the creatinine-based Schwartz bedside formula (2009), the cystatin C-based Caucasian Asian Pediatric and Adult cohort (CAPA) equation and the combined Full-Age Spectrum (FAS) formula as modified by Pottel. We analysed the agreement between them using the Bland–Altman method and the kappa statistic. We measured the albumin level in urine, the urine volume adjusted to 100 mL of GFR and blood pressure. We performed univariate and multivariate analyses of the risk factors associated with CKD. ResultsThe sample included 52 patients with a median age of 9.21 years. Fifteen (28.8%) had AKI. Five (10%) had CKD and the only associated risk factor was acute liver failure at the time of LT (odds ratio, 8.57; P = 0.04). There was poor agreement between the different estimation formulas. One patient was classified as having CKD with the Schwartz formula compared to four patients with the CAPA and the Pottel combined FAS formulas. Up to 42% of children without CKD had some positive marker of kidney injury. ConclusionsThe exclusive use of the 2009 Schwartz bedside formula to estimate GFR may lead to underdiagnosis of CKD in children post LT. Other markers of kidney injury are common, and their detection may help prevent the progression of CKD.

Intrahepatic cholangiocarcinoma: The role of liver transplantation, adjunctive treatments, and prognostic biomarkers.

Intrahepatic cholangiocarcinoma (iCCA) is a primary epithelial cell malignancy of the liver with rising incidence rate globally. Its insidious presentation, heterogeneous and aggressive biology, and recalcitrance to current therapies results in unacceptably high morbidity and mortality. This has spurred research efforts in the last decade to better characterize it molecularly with translation to improved diagnostic tools and treatments. Much of this has been driven by patient advocacy. This has renewed interest in orthotopic liver transplantation (LT) with adjunctive therapies for iCCA, which was historically disparaged due to poor recipient outcomes and donor organ scarcity. However, the optimal use of LT as a treatment for iCCA care remains unclear. Here, we review the epidemiology of iCCA, the history of LT as a treatment modality, alternative approaches to iCCA local control, the evidence for peri-operative systemic therapies, and the potential roles of biomarkers and targeted agents. In doing so, we hope to prioritize areas for continued research and identify areas where multidisciplinary care can improve outcomes.

COVID Cholangiopathy Can Occur Despite Mild COVID

Abstract Introduction/Objective Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19. Methods/Case Report Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts; repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic. Results (if a Case Study enter NA) NA. Conclusion Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.

Abstract 14084: Safety and Outcomes of Percutaneous Coronary Intervention in Patients Presenting With Acute Coronary Syndrome With Prior Liver Transplantation

Background: There is a paucity of data about the outcomes of performing Percutaneous coronary intervention (PCI) for Liver transplant (LT) patients presenting with acute coronary syndrome (ACS). Methods: We queried the national readmission database for patients who underwent PCI hospitalized between 2016 and 2019, patient were classified into two groups based on prior LT status. International classification of disease codes (ICD-10) were used for diagnosis and procedures codes. Our outcomes were In-hospital mortality and 90-day readmission rate. A multivariate adjusted regression model was performed to risk adjust for predictors of 90-day readmission (all-cause). Results: A total of 1400,861 patients underwent PCI between the years 2016 and 2019 for ACS and underwent PCI. 1,532 patients had a history of LT (0.1%). Hospitalized patients with prior LT were of similar age (65.2 ±0.31 vs 65.3 ±0.04 years, p=0.9), and less likely to be women (20.8.6% vs. 32.5%, p<0.01) compared with those without prior LT history. Hospitalized patients with prior LT had similar In-hospital mortality rate (3.9% vs 2.9%, p=0.3), shock (5.3% vs 4.5%, p=0.34), and Mechanical circulatory support utilization rate (4.9% vs 4.3%, p=0.452) but longer length of stay (5.8±0.3 vs 4.1±0.02, P<0.001) compared to the cohort that had no prior LT. Patients with prior LT had a higher readmission rate within 90 days 29.6% vs 19.4%, p= 0.001), and were less likely to have repeat PCI in the readmission (7.9% vs 12.3%, p<0.001), however more likely and acute kidney injury. Both cohorts had similar rates of acute heart failure exacerbation, bleeding complications, or in-hospital mortality in the readmission. Conclusion: There was no significant difference in mortality between both cohorts, however, readmission rate was higher in the LT cohort, Further studies exploring these differences may help to mitigate these readmissions.

COVID-19 infection in liver transplant recipients: Clinical features and outcomes from a Canadian multicentre cohort.

BACKGROUND: Prior studies have assessed risk factors and clinical outcomes in liver transplant (LT) recipients infected with COVID-19 globally; however, there is a paucity of Canadian data. Our multicentre study aims to examine the characteristics and clinical outcomes of LT patients with COVID-19 infection in Canada. METHODS: Adult LT recipients with reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19, from Canadian tertiary care centres between March 2020 and June 2021 were included. RESULTS: A total of 49 patients with a history of LT and COVID-19 infection were identified. Twenty-nine patients (59%) were male, median time from LT was 66 months (IQR 1-128), and median age was 59 years (IQR 52-65). At COVID-19 diagnosis, the median alanine transaminase (ALT) was 37 U/L (IQR 21-41), aspartate aminotransferase (AST) U/L was 34 (IQR 20-37), alkaline phosphatase (ALP) U/L was 156 (IQR 88-156), total bilirubin was 11 μmol/L (IQR 7-14), and international normalized ratio (INR) was 1.1 (IQR 1.0-1.1). The majority of patients (86%) were on tacrolimus (monotherapy or combined with mycophenolate mofetil); median tacrolimus level at COVID-19 diagnosis was 5.3 μg/L (IQR 4.0-8.1). Immunosuppression was modified in eight (16%) patients post-infection. Eighteen patients (37%) required hospitalization, and three (6%) required intensive care unit (ICU) admission and mechanical ventilation. Four patients (8%) died from complications related to COVID-19 infection. On univariate analysis, neither age, sex, comorbidities, nor duration post-transplant were associated with risk of hospitalization or ICU admission. CONCLUSIONS: LT recipients with COVID-19 have high rates of hospitalization but fortunately have low rates of ICU admission and mortality in this national registry.

Liver transplantation in patients with liver failure: Twenty years of experience from China.

Liver transplantation (LT) is the only effective method of treating end-stage liver disease, such as various types of liver failure. China has the largest number of patients with hepatitis B virus-related disease, which is also the main cause of liver failure. From the first LT performed in 1977, and especially over the past two decades, LT has experienced rapid development as a result of continuous research and innovation in China. China performs the second-highest number of LTs every year worldwide, and the quality of LT continues to improve. Starting January 1, 2015, all donor's livers have been from deceased donors and familial donors. Thus, China entered into a new era of LT. However, LT is still a challenging procedure in China. In this review, we introduced the brief history of LT in China, the epidemiology, aetiology and clinical outcomes of LT for liver failure in China and summarized the experience of LT from Chinese LT surgeons and scholars. The future perspectives of LT were also discussed, and it is expected that China's LT research could be further integrated elsewhere in the world.

A224 COVID-19 INFECTION IN LIVER TRANSPLANT RECIPIENTS: CLINICAL FEATURES, HOSPITALIZATION, AND MORTALITY FROM A CANADIAN MULTICENTRE COHORT

BackgroundThe COVID-19 pandemic has brought significant challenges to clinicians caring for liver transplant (LT) recipients. Researchers have sought to better understand the risk and clinical outcomes of LT recipients infected with COVID-19 globally, however, there is a paucity of data from within Canada.AimsOur multi-center study aims to examine the characteristics and clinical outcomes of LT patients with COVID-19 in Canada.MethodsWe identified a retrospective cohort of adult LT recipients with RT-PCR confirmed COVID-19 from 7 Canadian tertiary care centers between March 2020 and June 2021. Demographic and clinical data were compiled by clinicians within those centers. We identified liver enzyme profile at the time of COVID-19 infection, immunosuppression type and post-infection adjustments, rate of hospitalization, ICU admission, mechanical ventilation, and death.ResultsA total of 49 patients with a history of LT and COVID-19 infection were identified. Twenty nine patients (59%) were male, the median time from LT was 66 months (1, 128) and the median age at COVID-19 infection was 59 years (52, 65). At COVID-19 diagnosis, the median ALT was 37 U/L (21, 41), AST U/L was 34 (20, 37), ALP U/L was 156 (88, 156), Total Bilirubin was 11 umol/L (7, 14), and INR was 1.1 (1.0, 1.1). The majority of patients (92%) were on tacrolimus monotherapy or a combination of tacrolimus and mycophenolate mofetil (MMF); median tacrolimus level at COVID-19 diagnosis was 5.3 ug/L (4.0, 8.1). Immunosuppression was modified in 8 (16%) patients post-infection; either the tacrolimus dose was reduced or MMF was held. One patient developed acute cellular rejection which recovered after re-initiation of the prior regimen. Eighteen patients (37%) required hospitalization, 6 (12%) were treated with dexamethasone, and 3 (6%) required ICU admission and mechanical ventilation. Four patients (8%) died due to complications of COVID-19. On univariate analysis, neither age, sex, co-morbidities nor duration post-transplant were associated with risk of hospitalization.ConclusionsIn our national retrospective study, approximately 40% of patients required hospitalization with a mortality rate of < 10%. Previous studies have shown proximity to LT as an independent factor for mortality with COVID-19; the median time from LT for our patients was 5 years, which may explain the lower mortality rate. Of note, the median tacrolimus levels were much lower in comparison to the target of 8–10 ug/L used in the first year post-transplant. As the landscape of COVID-19 changes with vaccination, evolving treatments, and increasing rates of variant transmission, additional studies are required to continue identifying trends in clinical outcomes.Funding AgenciesNone

Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis.

To advance our understanding of monogenic forms of intrahepatic cholestasis. Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data. Ninety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported. In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.

Clinical Characteristics, Hospitalization, and Mortality Rates of Coronavirus Disease 2019 Among Liver Transplant Patients in the United States: A Multicenter Research Network Study

Clinical Characteristics, Hospitalization, and Mortality Rates of Coronavirus Disease 2019 Among Liver Transplant Patients in the United States: A Multicenter Research Network Study

A Changing Etiologic Scenario in Liver Transplantation: A Single-Center Cohort Study From Turkey

PurposeNonalcoholic steatohepatitis (NASH) is an increasing cause of liver transplantation (LT) worldwide, especially in Europe and North America. In this study, we aimed to investigate the changing pattern of etiologic causes of LT in our center for the past 15 years. Materials and methodsA cohort of 967 consecutive adult patients with history of LT between 2004 and 2018 in our center was reviewed regarding etiologies for LT. All patients who had a transplant during this time frame were divided into 3 time periods as follows: 2004 to 2009, 2010 to 2013, and 2014 to 2018. All explanted liver samples were sent to pathology for establishment of a definitive etiologic cause. ResultsChronic hepatitis B virus (HBV) infection was the leading cause of LT in the overall cohort (37%), followed by hepatitis C virus (HCV) infection (11%), and alcoholic liver disease (9.5%). NASH accounted for 7.5% of the cases. While HBV decreased from 44% in 2004 to 2009 to 36% in 2014 to 2018, NASH increased from 1.1% to 9.4% in overall transplants during the same period, accounting for one-third of the etiologies for LT following HBV and HCV. ConclusionsThere might be a global changing figure regarding etiology for LT in Turkey, especially NASH, which is the fastest growing cause of LT. However, this topic needs to be evaluated in large cohort series from collaborative multicenter studies from Turkey.

Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: the Mayo Clinic experience.

Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3-21.1) and 1.8 (0.7-21.1) months, respectively. In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.

PTU-035 Endoscopic treatment of biliary anastomotic strictures in patients with liver transplant. a terciary centre experience

<h3>Introduction</h3> Biliary anastomotic strictures are a frequent complication of liver transplantation (LT), that is associated with important morbidity and high costs. ERCP is considered the treatment of choice, however, the optimal management of these patients has not yet been shown. <h3>Objective</h3> To evaluate the efficacy and complicaitons of endoscopic treatment with ERCP of patients with LT and stricture of biliary anastomosis, and to identify predictors of good response to endoscopic treatment. <h3>Method</h3> Retrospective study, which included all patients with previous history of LT and subsequent diagnosis of biliary anastomotic stenosis and underwent ERCP between January 2002 and December 2013. Good response was defined as total resolution of the stricture with no need of further interventions. <h3>Results</h3> 103 patients were included in the study, 79 (77%) were men, mean age of 53 years (range 35 to 70 years). The most frequent indications for LT were hepatocellular carcinoma (33%), alcoholic cirrosis (20.4%) and hepatitis C (18%). 44% of the patients presented early anastomotic stricture, that developed after a mean time of 79 weeks after LT. Furthermore, 4% of the patients associated a biliary fistula. The mean number of ERCP sessions was 3,4 (range 1–10), with mean success rate of 80%. As for the endoscopic technique, endoscopic dilatation was performed in 77% of cases (mean number of dilatations of 1,9); plastic stent was placed in 73% (average 3,9 stents per patient), and in 16% of the patients, plastic stents were initially placed and changed for metalic stents in subsequent ERCPs (1,5 stents per patient). The complication rate was of 9,1%: migration of stent was observed in 11 cases (10 plastic stents and 1 metal stent); colangitis/bacteriaemia in 3,1%, pancreatitis in 3,1%, bleeding in 1,1% and perforation in 0,3%. Two patients died as a direct complication of ERCP, both due to pancreatitis. 57 patients (55%) presented complete response to endoscopic treatment, with posterior reappearance of stricture in 11 (11%) cases, and 31 patients did not respond, 17 of those underwent surgery. <h3>Conclusion</h3> In our experience, ERCP is a reasonably safe technique of treatment of biliary strictures in LT patients, that can avoid surgical procedures in a high proportion of them. <h3>Disclosure of interest</h3> None Declared.

The challenges of liver transplantation for hepatocellular carcinoma on cirrhosis

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and liver transplantation (LT) has potentials to improve survival for patients with HCC. However, expansion of indications beyond Milan Criteria (MC) and use of bridging/downstaging procedures to convert intermediate-advanced stages of HCC within MC limits are counterbalanced by graft shortage and increasing use of marginal donors, partially limited by the use of donor-division protocols applied to the cadaveric and living-donor settings. Several challenges in technique, indications, pre-LT treatments and prioritization policies of patients on the waiting list have to be precised through prospective investigations that have to include individualization of prognosis, biological variables and pathology surrogates as stratification criteria. Also, liver resection has to be rejuvenated in the general algorithm of HCC treatment in the light of salvage transplantation strategies, while benefit of LT for HCC should be determined through newly designed composite scores that are able to capture both efficiency and equity endpoints. Innovative treatments such as radioembolization for HCC associated with portal vein thrombosis and molecular targeted compounds are likely to influence future strategies. Accepting this challenge has been part of the history of LT and will endure so also for the future.