Years Of Liver Transplantation Research Articles

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with Primary Biliary Cholangitis- an ELTR study

BackgroundTacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the relation between the type of calcineurin inhibitor (CNI) and long-term outcomes following LT in patients with PBC. MethodsSurvival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the dataset of the European Liver Transplant Registry. Patients who received a donation after brain death (DBD) graft between 1990 and 2021 with at least one year of event-free follow-up were included. ResultsIn total, 3175 PBC patients were followed for a median duration of 11.4 years (IQR 5.9 – 17.9) after LT. Tacrolimus (Tac) was registered in 2056 (64.8%) patients and cyclosporin (CsA) in 819 (25.8%). Adjusted for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (aHR 1.07, 95%CI 0.92-1.25, p=0.402) or death (aHR 1.06, 95%CI 0.90-1.24, p=0.473) over CsA. In this model maintenance mycophenolate was associated with a lower risk of graft loss (aHR 0.72, 95%CI 0.60-0.87, p<0.001) or death (aHR 0.72, 95%CI 0.59-0.87, p<0.001), while these risks were higher with use of steroids (aHR 1.31, 95%CI 1.13-1.52, p<0.001, and aHR 1.34, 95%CI 1.15-1.56, p<0.001, respectively). ConclusionsIn this large LT registry, type of CNI was not associated with long-term graft or recipient survival, reassuring us to continue the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that threshold for combination treatment with Tac and MMF should be low. Impact And ImplicationsThis study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following DBD liver transplantation (LT). While tacrolimus has been previously related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patient transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings reassure physicians on the continued use of Tac after LT in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Incidence and risk factors of graft-versus-host disease after liver transplantation: A national study 2010-2020.

Graft-versus-host disease (GVHD) is a common complication of hematopoietic cell transplantation, and its incidence is low in liver transplantation (LT). Estimating the incidence of GVHD after LT is challenging due to the paucity of available data from the United Network for Organ Sharing. This is the first national analysis of the incidence and risk factors of GVHD after LT. This retrospective cohort study used the National Readmission Database to calculate the incidence rate of GVHD within 1 year of LT using survival analysis. The predictors of GVHD were identified using univariate and multivariate Cox regression analyses. From 2010 to 2020, of 88,433 LTs, 383 cases of GVHD occurred within 1 year after LT, resulting in an incidence rate of 1.0% (95% CI: 0.8%-1.3%). We observed no statistically significant change in the incidence of GVHD after LT from 2010 to 2020 (beta-coefficient, -0.07%; 95% CI: -0.17% to 0.04%, p = 0.188). Interestingly, alcohol-associated liver disease was associated with a lower risk of GVHD (adjusted HR, 0.57; 95% CI: 0.36-0.91, p = 0.018), whereas a higher risk was found to be related to a secondary diagnosis of COVID-19 on index admission. Our study found that the incidence rate of GVHD within 1 year of LT in the United States was 1.0% and remained stable from 2010 to 2020. The predictors associated with GVHD include alcohol-associated liver disease and COVID-19. Our study provides valuable insights into the incidence, risk factors, and outcomes of GVHD after LT.

No Additional Risk of Ampicillin Rash Among Pediatric Liver Transplant Recipients With Concurrent Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV) infection frequently develops in children undergoing liver transplantation (LT) because of mandated immunosuppressive therapy. There is a risk of ampicillin rash when penicillin derivatives are used in patients with EBV-associated infectious mononucleosis. Hence, the administration of penicillin derivatives may raise concerns about ampicillin rash in patients with high EBV loads. However, no studies confirmed the risk of administering penicillin derivatives to EBV-infected children after LT. This retrospective study was conducted at the largest pediatric transplantation center in Japan. We investigated all pediatric liver transplant recipients who received penicillin derivatives within 2 years of LT between 2014 and 2020. We separated the cohort into EBV-positive and EBV-negative groups to assess the frequency of ampicillin and antibiotic-associated rash. Two hundred eighty-six liver transplant recipients were enrolled. There were 111 recipients in the EBV-positive group and 175 recipients in the EBV-negative group. In the EBV-positive group, 49 patients had high EBV DNA loads (≥1000 copies/µg DNA). None of the patients in either group developed ampicillin rash, and the frequency of antibiotic-associated rash did not differ [8/111 (7.2%) vs. 10/175 (5.7%), P = 0.797]. Additional subgroup analysis revealed no difference in the frequency of antibiotic-associated rashes regardless of the presence or absence of high EBV loads. In this study, ampicillin rash was not observed, and antibiotic-associated rash was not associated with concurrent EBV infection. Penicillin derivatives can be used safely, even in liver transplant recipients with persistent asymptomatic EBV infection.

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations.

Fas ligand (FasL) is one ligand that activates extrinsic apoptosis pathway. High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation (LT). No high blood concentrations of soluble FasL (sFasL) have been found in patients with acute LT rejection; however, the samples size of those studies was small. To determine whether patients with hepatocellular carcinoma (HCC) that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size. Patients underwent LT due to HCC were included in this retrospective study. Serum sFasL levels prior to LT were measured and one-year LT mortality was registered. Non-surviving patients (n = 14) showed higher serum sFasL levels [477 (269-496) vs 85 (44-382) pg/mL; P < 0.001] than surviving patients (n = 113). Serum sFasL levels (pg/mL) were associated with mortality (OR = 1.006; 95%CI = 1.003-1.010; P = 0.001) independently of age of LT donor in the logistic regression analysis. We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

Arterial Lactate Concentration at the End of Liver Transplantation is Independently Associated With One-Year Mortality

Liver transplant patients who develop hyperlactatemia are at increased risk of postoperative morbidity and short-term mortality, but there are few data on longer-term outcomes. We therefore investigated if arterial lactate concentration obtained immediately after surgery, at the time of admission to the intensive care unit (ICU), was associated with 1-year mortality. In this retrospective cohort study, all patients who underwent liver transplant surgery from a deceased donor between September 2013 and December 2019 were screened for inclusion. Patients who underwent combined transplantation surgery and those with a history of previous liver transplantation (ie, redo surgery) were not included. Logistic regression modeling included univariate and multivariate analyses. Receiver operating characteristic curves and areas under the curves were calculated. Lactate thresholds and association with outcome were analyzed for specificity, sensitivity, and Youden's index. Of 226 patients included, 18.4% died within 1 year of liver transplantation. Immediate postoperative lactate concentration was independently associated with 1-year mortality with an adjusted odds ratio of 1.35 (95% CI 1.16-1.59; P < .001) per mmol/L increase in lactate and an area under the curve of 0.80 (95% CI 0.72-0.87; P < .001). A lactate concentration of 2.25 mmol/L (cutoff determined using Youden's index) was associated with increased 1-year mortality with a sensitivity of 0.71 and a specificity of 0.72. Increased arterial lactate concentration on admission to the intensive care unit immediately after orthotopic liver transplantation is independently associated with increased 1-year mortality.

Donation after Circulatory Death Grafts Have Comparable Outcomes to Donation after Brain Death Grafts in Liver Transplantation

Introduction: In the United States, 30% of donation after circulatory death (DCD) grafts are discarded for liver transplantation (LT). DCD grafts can mitigate liver organ shortage but is underused due to the believe of poor outcomes in graft and patient survival. Recent studies have shown comparable outcomes to donation after brain death (DBD). The aim of this study is to review our experience with the use of DCD grafts. Methods: Retrospective single center study, whole grafts transplanted between January 2014 and December 2021 were included. Propensity score match was done using recipient age, recipient gender, MELD score, wait time, number of previous LT, cold ischemia time, year of LT and surgeon as cofounders. Multivariate Cox-regression models were created with significant variables in the univariate analysis. Finally, Kaplan-Meier curves with log-rank test were performed. Results: A total of 63 DCD and 148 DBD grafts were included. The patients were predominantly males (59.2%), median age was 58 (IQR 49-65), the most common reason for transplantation was alcoholic cirrhosis (20.4%) and were listed for their first LT (95.7%). Number of transplants (HR:15.39, 95%CI: 3.56-66.49, p < 0.001) and BMI (HR:1.1, 95%CI: 1.01-1.2, p = 0.03) were associated to graft loss. DCD was not associated with graft (HR:0.47, 95%CI: 0.14-1.58, p = 0.2) or patient (HR:0.33, 95%CI: 0.08-1.42, p = 0.1) survival. Graft (92.9% DBD vs 96.8% DCD, p = 0.2) and patient (93.6% DBD vs 100% DCD, p = 0.1) 2-year survival were similar. Conclusion: When matching different cofounders, the use of DCD grafts has comparable outcomes to those DBD grafts.

P9.04: Evaluation of Quality of Life in Adult Patients After One Year Liver Transplantation

Introduction: Liver transplantation (LT) aims not only to obtain long survival, but also to achieve an excellent quality of life (QOL). The purpose of our study is to assess several QOL aspects of recipients after 1 year of LT and to identify potential factors that might be associated with impaired QOL. Materials and Methods: Retrospective analysis including LT between 2013 to 2021. The Liver Disease Quality of Life questionnaire (LDQOL 1.0), and the consent form to participate of this study were given personally or sent by e-mail. This questionnaire includes 111 items distributed within 20 domains. Fulminant liver failure, hepatorenal transplantation and underaged patients were excluded. Significance was explored using T tests. Differences were considered statistically significant at p < 0.05. Results: This study included 89 patients out of 360 LT (56% male) who answered the survey, age range 24.8–75 years (mean: 52.5). On average, the patients had to wait 360 days before undergoing LT. Primary etiologies of liver disease were: hepatitis C virus (22.5%), alcohol (22.5%), autoimmune cirrhosis (22.5%), primary biliary cirrhosis (14.6%), NASH (6.7%), primary sclerosing cholangitis (3.3%), cryptogenic (2.2%), and others (5.6%). Thirty-one LT also presented hepatocarcinoma (HCC). The vast majority (93%) had moderate to severe liver disease, with 46% Child-Pugh B and 47% Child-Pugh C. After 1 year LT, QOL was improved resulting with a mean of 83,69%. The general well-being domain rated lowest with 69%. Higher scores (89 - 90%) were obtained on effects of liver disease, stigma of liver disease, physical limitations, emotional limitations and loneliness. There was a significant association between the Child-Pugh classification and body pain, emotional well-being, memory and stigma of liver disease (p< 0,05). Lower MELD scores (<18) showed better results after 1 year LT in energy/fatigue, emotional well-being, liver disease symptoms, effects of liver disease and hopelessness domains (p < 0,05). There was no significant difference when QOL was compared according etiology of chronic liver disease, gender, or age. Conclusion: After 1 year of LT, patients result on QOL show a significant improvement, even similar to results published on the common population, in most of the domains surveyed except for body pain, energy and emotional well-being which still need upgrade.

SAT234 - A predictive model for mortality within one year of liver transplantation at the time of wait-listing for transplant: a novel approach using machine learning algorithms in a large US multi-ethnic cohort

SAT234 - A predictive model for mortality within one year of liver transplantation at the time of wait-listing for transplant: a novel approach using machine learning algorithms in a large US multi-ethnic cohort

The first years of liver transplantation: experiences at a single center.

BackgroundThe aim of this study was to analyze the first stages of progress in liver transplantation (LT) at a single center in Vietnam.MethodsThis study analyzed data from patients and donors who participated in the LT program between August 2018 and December 2021 at University Medical Center, Ho Chi Minh City. Study measures included any difficulties encountered, as well as the post-LT outcomes for living donor LT (LDLT) and deceased donor LT (DDLT). The chi-square test and Kaplan Meier survival analysis were used to test the factors that influenced the outcomes.ResultsA total of 18 adult recipients with LT (LDLT, n=16; DDLT, n=2) were included (mean age, 55.2±2.6 years; male, 88.9%). The most common post-LT complications were middle hepatic venous stenosis (20%) and graft rejection (22.2%). These complications were observed in LDLT patients. For DDLT, graft rejection (50%) was the only complication recorded. The survival rates for recipients at 3 months, 6 months, and 1 year were 100%, 88.9%, and 88.9%, respectively. The LDs had their right livers without the middle hepatic veins harvested, and biliary leakage (6.25%) was the only complication observed. There were no deaths among recipients or LDs during the operations or hospital stays.ConclusionsThis study provides key details about the process of LT, and these positive outcomes support LT as an important therapy for end-stage liver disease and early hepatocellular carcinomas.

DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation.

BACKGROUNDOxidative damage of DNA and RNA has been associated with mortality of patients with different diseases. However, there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).AIMTo determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.METHODSPatients with HCC who underwent LT were included in this observational and retrospective study. Serum levels of all three oxidized guanine species (OGS) were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation. LT mortality at 1 year was the end-point study.RESULTSSurviving patients (n = 101) showed lower serum OGS levels (P = 0.01) and lower age of the liver donor (P = 0.03) than non-surviving patients (n = 13). An association between serum OGS levels prior to LT and 1-year LT (odds ratio = 2.079; 95% confidence interval = 1.356-3.189; P = 0.001) was found in the logistic regression analysis.CONCLUSIONThe main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

Impact of pretransplant malnutrition on short-term clinical outcomes of liver transplantation - An exploratory study

Introduction: Malnutrition is highly prevalent among patients undergoing liver transplantation (LT) and can affect various clinical factors. The present study focuses on the impact of pretransplant malnutrition on various short-term outcomes of LT. Methods: Ninety LT recipients undergoing elective living donor LT were recruited in the study. Based on subjective global assessment (SGA), they were grouped as normal, moderate, and severely malnourished. Information regarding prognostic factors (Child-Turcotte-Pugh [CTP] and Model for End-Stage Liver Disease [MELD] scores), biochemical parameters (hemoglobin, TLC, platelets, bilirubin [T], serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, albumin, creatinine, and sodium), dietary intake, % weight loss, and short-term outcomes (hospital stay, intensive care unit days, blood unit usage during surgery, and dead and alive status after 1 year) were gathered. Results: The recipient evaluation showed that 54.4% of the patients were moderately malnourished and 27.8% of the patients were severely malnourished. The prognostic scores, CTP, and MELD significantly had higher scores in moderately and severely malnourished patients (P < 0.001 and P = 0.003). Among the biochemical parameters, hemoglobin, albumin, and sodium showed significantly lower levels in moderately and severely malnourished patients (P < 0.001, P = 0.02, and P = 0.01). The data also showed a significantly higher degree of ascites, % weight loss, and lower calorie intake among malnourished patients. A higher degree of malnutrition was associated with poor outcomes of LT; higher hospital stay (P = 0.014), packed red blood cell unit usage during surgery (P = 0.005), and deaths after 1 year of LT (P = 0.03). Conclusion: Pre-LT malnutrition by SGA was associated with poor short-term outcomes of LT with higher hospital stay and deaths. Hence, the present data emphasize the need for early nutrition intervention for improved surgery results.

Oncological Evaluation Using Circulating Tumor Cells and PET-CT of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. Liver transplantation (LT) is potentially the best curative therapeutic option in selected cirrhotic patients (Milan criteria). Nevertheless, the recurrence rate is high (10-20%) and there are not efficient markers of biological pretransplant activity. Aim: to determine the number of CTCs in patients with HCC awaiting for LT, to study its possible association with AFP levels, positivity of PET-CT and clinical variables (vascular invasion, tumor size, waiting list time, post-LT recurrence…) and to compare CTC levels before and after LT (one and six months and one and two years). Method: Peripheral blood was obtained from 30 patients included in the waiting list and after 1 and 6 months and 1 and 2 years of the LT. CTCs immunomagnetic isolation was performed with anti-EpCAM antibodies by IsoFlux™ system. Statistical analysis: Rho Spearman test, Mann-Whitney U test and Wilcoxon test were used when appropriate (SPSS 22.0;Inc;USA). Results: A total of 30 patients with HCC within Milan criteria were included. The median follow-up was 57 months (IQR: 45-62). Four patients (13.3%) had a recurrence. Before LT, at least one CTC was counted in 24 patients (80%). The average concentration of CTCs before LT was 9(IR:0-93) CTCs/10 ml. At 1 and 6 months, 1 and 2 years of LT, CTC levels were 4(IR:1-22), 3(IR:0-20), 2(IR:0-6) and 3(RI:1-9) CTCs/10 ml respectively. Statistically significant differences were found between pre-LT levels and CTC levels at one year (Z = - 2.375;p = 0.018) and at 2 years (Z = - 2.076;p = 0.038).Pre-LT levels of CTC were associated with a prolonged time on the waiting list (rs = 0.550;p = 0.002), positive PET-CT (U = 25;z = - 2.250;p = 0.024), larger tumor size (rs = 0.570;p = 0.001), increase in the sum of the diameters of viable tumors (rs = 0.487;p = 0.006) and presence of microvascular invasion (U = 10;z = - 2.130;p = 0.033). The recurrence-free survival was lower in patients with SUVmax≥3.5 (log-rank 14.6;p<0.001) and pre-LT CTC levels≥9 (log-rank 4.2; p = 0.040). A correlation was found between CTC levels and the days on waiting list (p = 0.002), tumor size (p = 0.001), positive PET-CT (p = 0.024) and presence of microvascular invasion (p = 0.033). Recurrence-free survival was lower in patients with CTCs ≥ 9 (p = 0.040). Conclusion: CTC levels in patients with HCC undergoing LT are associated with clinical and pathological factors of poor prognosis.CTC levels decrease significantly after LT.

Quality of Life after 10 Years of Liver Transplantation.

This study goal was to evaluate the long-term quality of life of patients who underwent cadaveric liver transplants (CLT) in two Brazilian hospitals. Medical records of all patients who underwent CLT and survived over 10 years were revised. The international validated questionnaire Short-Form 36 was employed to assess the quality of life. Patients data were obtained from electronic medical records and study protocols. A total of 342 patients underwent CLT, of which 129 were alive and 93 fully answered the questionnaire and were included in the study. The group consisted of 62 men (66.6%) and 31 women (33.4%), with average age of 40.1±15.9 years. Follow-up time was 16±4.1 years. The most common indication of CLT was hepatic cirrhosis caused by hepatitis C virus, 24.7%. Transplanted patients had lower scores than the general population in mental health [62.9 (95%CI: 60.1-65.7,) vs. 74.5, p < 0.001]. In all other domains, transplanted patients had similar (emotional aspect limitiation, pain, and general health status) or superior (physical aspect limitation, social aspects, functional capacity, and vitality) scores than the general population. Functional capacity score was lower in patients with long-term complications, who were aged more than 50-years, and unemployed. The quality of life in patients with more than 10 years after CLT was similar or superior than the general population, except for the mental health domain.

S1106 Early Detection of Hepatocellular Carcinoma Recurrence in the Post-Transplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System

INTRODUCTION: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases, however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally-validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS. METHODS: We conducted a retrospective cohort study of adult patients with HCC who underwent LT. The RETREAT score was classified as follows: low risk (scores 0-3), moderate risk (score 4), and high risk (score 5 or higher). The CCFSS is based on explant pathology and categorized as: low (score 1), moderate (score 2), and high risk (score 3). Mantel- Haenzsel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence. RESULTS: A total of 52 patients with HCC underwent LT. The median follow-up period was 37 months. The median age of the patient population was 65.5 years (range 30-74 years) and 75% were male. The most common underlying liver disease was hepatitis C (n = 29, 55.8%), followed by fatty liver disease (n = 13, 25%). On explant pathology, 41 patients (78.8%) had viable tumor size <5 cm, two patients (3.8%) had ≥5 cm tumor size and the rest had a complete pathological response. Sixteen patients (31%) showed microvascular invasion. In 14 patients (31%), the tumors were poorly differentiated. Thirty-four patients (65.4%) had only one or no HCC lesions on explant pathology. Four patients had post-LT HCC recurrence, all within 2 years of LT (Table 1). Both risk scores had a sensitivity of 75%; the specificity of RETREAT score was 95.8% while the specificity of CCFSS was 60.4%. The RETREAT score was better able to detect low, moderate and high levels of risk (P < 0.001), compared to the CCFSS score (P = 0.480). AFP levels at the time of LT were associated with HCC recurrences (P = 0.014). Patient age, gender, ethnicity, liver disease etiology, MELD scores, HCC lesions at the time of diagnosis, and number/type of locoregional therapy (LRT), were not predictive of HCC recurrence. CONCLUSION: This is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than CCFSS. The incorporation of AFP levels at the time of LT improves the estimation of HCC recurrence in the post-LT period.Table 1

Effect of Hepatitis C Virus Treatment on Rejection Incidence and Severity in Post-Liver Transplant Recipients

Abstract Background and Aims HCV is a worldwide cause of chronic liver disease, particularly in Egypt where the most prevalent is genotype 4. HCV-associated cirrhosis is the most common indication for orthotopic liver transplantation (OLT) among adults. HCV infection remains a problem after transplantation, and recurrent hepatic infection is the leading cause of graft failure. Little is known about the long-term effects of direct acting antiviral therapy in patients after liver transplantation. We examined the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with DAAs relative to the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with Interferon based therapy and patients who didn’t receive any treatment for HCV after transplantation. Patients and Methods The study was conducted on 90 patients who had underwent liver transplantation between 2010 and 2017 at Ain Shams Center for Organ Transplantation (ASCOT) with a minimum follow up period of 6 months. Patients were divided into three groups: group I included 16 patients that didn’t receive antiviral treatment after liver transplantation, group II included 20 patients that had received interferon based therapy after liver transplantation and group III included 54 patients that had received direct acting antivirals after liver transplantation. Results Amongst group I, 2 patients (12.5%) developed acute graft rejection while in group II 2 patients (10%) developed chronic graft rejection and in group III 6 patients (11.11%) developed chronic rejection. In group I, all the patients (100%) had developed rejection that was diagnosed within one year of liver transplantation. In group II, 2 patients (100%) developed chronic graft rejection which occurred after one year of liver transplantation, one of them was on treatment with peg interferon and the other had already completed treatment. In group III, 2 patients (40%) had developed chronic rejection within one year of transplantation, while 4 patients (60%) had developed chronic rejection after one year of transplantation. One patient (16.67%) had developed rejection on treatment while 5 patients (83.33%) had developed rejection after the end of treatment. Conclusion It was found that the incidence of chronic rejection was more in patients that had received antiviral treatment after liver transplantation, however no difference was noted between DAAs and peg-interferon. Chronic rejection was found to be more common when treatment was given over one year after liver transplantation (6 cases) as compared to within the 1st year (2 cases). This may be related to the withdrawal of immunosuppression treatment after one year of transplantation and maintenance on monotherapy.

Pediatric Liver Transplantation: Then and Now

This paper reviews the past 50 years of liver transplantation in children from the perspective of patient demographics, perioperative patient management, surgical techniques, immunosuppression and patient outcomes.

Hepatocellular Carcinoma with Increased AFP Levels and Extrahepatic Manifestation after Liver Transplantation: A Case of Late-Onset Recurrence

Liver transplantation is the best treatment modality in patients with hepatocellular carcinoma. The major concern after liver transplantation for hepatocellular carcinoma treatment is recurrence, because it’s the most important factor for the long term survival. There are two forms of recurrence; early-onset (within 2 years of liver transplantation) and late-onset (after 2 years of liver transplantation). A lot of factors have been reported in the literature to foresee recurrence after liver transplantation and one of them is alpha-fetoprotein. Many studies have shown that high levels of pre-transplant alpha-fetoprotein is related to early-onset recurrence and worse outcomes in the long term. In this case report, we report a case of late-onset recurrence, despite having high levels of pre-transplant alpha-fetoprotein in contrary to the literature, and still survive with a high quality of life 6 years after transplantation.

Deletion of donor-reactive T cell clones after human liver transplant.

We recently developed a high throughput T cell receptor β chain (TCRβ) sequencing-based approach to identifying and tracking donor-reactive T cells. To address the role of clonal deletion in liver allograft tolerance, we applied this method in samples from a recent randomized study, ITN030ST, in which immunosuppression withdrawal was attempted within 2years of liver transplantation. We identified donor-reactive T cell clones via TCRβ sequencing following a pre-transplant mixed lymphocyte reaction and tracked these clones in the circulation following transplantation in 3 tolerant and 5 non-tolerant subjects. All subjects showed a downward trend and significant reductions in donor-reactive TCRβ sequences were detected post-transplant in 6 of 8 subjects, including 2 tolerant and 4 non-tolerant recipients. Reductions in donor-reactive TCRβ sequences were greater than those of all other TCRβ sequences, including 3rd party-reactive sequences, in all 8 subjects, demonstrating an impact of the liver allograft after accounting for repertoire turnover. Although limited by patient number and heterogeneity, our results suggest that partial deletion of donor-reactive T cell clones may be a consequence of liver transplantation and does not correlate with success or failure of early immunosuppression withdrawal. These observations underscore the organ- and/or protocol-specific nature of tolerance mechanisms in humans.

Role of allelic imbalance in predicting the risk of hepatocellular carcinoma recurrence after liver transplantation

Background: Hepatocellular carcinoma (HCC) recurrence (HR) after liver transplantation (LT) remains a challenging issue, because HCC size and number tell only a partial tale of the characteristics that predict post-transplant outcomes. We aimed to analyze the allelic imbalance (or loss of heterozygosity) in specific microsatellites, and to assess the risk of HR. Methods: Seventy-one (71) patients who underwent LT for HCC at ISMETT were included in this retrospective study, 18 of whom developed HR at 5-years post-transplant. Molecular analysis, using 19 microsatellites, was done on whole blood and on the corresponding native liver. The presence of allelic imbalance for a specific locus (presence of loss of heterozygosity) was determined for values outside the normal range (0.66-1.50). Results: We found a statistically significant association between allelic imbalance and tumor recurrence only in 3 loci (D3S2303, D9S251, and D9S254). The evaluation of fractional allelic imbalance (FAI) cut-point index is associated with HR. ROC analysis indicated that this diagnostic test has good accuracy in terms of HR after LT. FAI index has correctly classified on average 74% of patients, predicted HR within 2 years of LT for 69% of patients, and confirmed the high predictive role of allelic imbalance in D9S251. Conclusion: Our data suggest that the information obtained by allelic imbalance analysis could have a prognostic application in risk management of HR in patients who have undergone LT, particularly for early HR.