Mortality In Liver Transplant Recipients Research Articles

The Effects of Sustained Immunosuppression Withdrawal After Liver Transplantation on Metabolic Syndrome.

Liver transplant (LT) recipients often experience adverse effects of immunosuppressive (IS) drugs, especially on metabolic profiles. Selected LT recipients can achieve successful IS withdrawal; however, its effects on metabolic syndrome (MS) are unknown. This is a retrospective single-center study investigating the incidence and/or regression of MS in 75 selected LT recipients who were previously enrolled in prospective IS withdrawal trials between 1999 and 2017. Patients who were transplanted due to nonalcoholic steatohepatitis/metabolic-associated fatty liver disease were excluded, as well as those with a follow-up <3 y after IS weaning. Forty-four patients (58.7%) achieved sustained withdrawal or minimization of immunosuppression (WMIS) and 31 patients (41.3%) required reintroduction of immunosuppression (no-WMIS). Among LT recipients who were metabolically healthy (n = 52, 69.3%) before the start of IS weaning, there was a significantly lower rate of de novo MS in WMIS patients compared with no-WMIS patients after 5 y (8.3% and 47.8%, respectively, P = 0.034). Of 23 LT recipients (30.7%) who had MS at the time of commencing IS withdrawal, complete regression of MS was observed in 47.1% of WMIS patients and in none (0%) of the no-WMIS patients after 5 y (P = 0.054). Furthermore, individual components of MS were better controlled in IS-weaned patients, such as arterial hypertension and abnormal serum lipids. Achievement of sustained IS withdrawal reduces the incidence of de novo MS development in metabolically healthy patients and increases the likelihood of MS regression in patients with established MS. The foreseeable long-term beneficial effects of these favorable metabolic changes on morbidity and mortality of LT recipients require further investigation.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care.

De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients. To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation. A literature search was conducted using MEDLINE and Embase databases using the key terms "solid organ transplantation", "tacrolimus", "mycophenolic acid", and "carcinogenicity", in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria. A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients. The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes.

With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d (P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC (P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

The triglyceride-glucose index: a novel predictor of stroke and all-cause mortality in liver transplantation recipients

BackgroundThe triglyceride-glucose (TyG) index, identified as a reliable indicator of insulin resistance (IR), was reported to be associated with stroke recurrence and morbidity in the general population and critically ill patients. However, the relationship in liver transplantation (LT) recipients remains unknown. This study aimed to investigate the correlation between the TyG index and post-LT stroke along with all-cause mortality and further assess the influence of IR on the LT recipients’ prognosis.MethodsThe retrospective cohort study enrolled 959 patients who underwent LT at a university-based medical centre between January 2015 and January 2021. The participants were divided into three groups according to their TyG index tertiles. The primary outcome was post-LT stroke. Multivariate logistic regression, COX proportional hazards regression, and restricted cubic spline RCS were used to examine the association between the TyG index and outcomes in LT recipients.ResultsWith a median TyG index of 8.23 (7.78–8.72), 780 (87.18% males) patients were eventually included. The incidence of post-LT stroke was 5.38%, and the in-hospital, 1-year, and 3-year mortality rates were 5.54%, 13.21%, and 15.77%, respectively. Multivariate regression analysis showed an independent association between the TyG index and an increased risk of post-LT stroke [adjusted odds ratio (aOR), 3.398 (95% confidence interval [CI]: 1.371–8.426) P = 0. 008], in-hospital mortality [adjusted hazard ratio (aHR), 2.326 (95% CI: 1.089–4.931) P = 0.025], 1-year mortality [aHR, 1.668 (95% CI: 1.024–2.717) P = 0.039], and 3-year mortality [aHR, 1.837 (95% CI: 1.445–2.950) P = 0.012]. Additional RCS analysis also suggested a linear increase in the risk of postoperative stroke with elevated TyG index (P for nonlinearity = 0.480).ConclusionsThe TyG index may be a valuable and reliable indicator for assessing stroke risk and all-cause mortality in patients undergoing LT, suggesting its potential relevance in improving risk stratification during the peri-LT period.

Cumulative exposure to tacrolimus during early period after liver transplantation does not affect the recurrence of hepatocellular carcinoma

The clinical effects of tacrolimus (TAC) exposure on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remain unclear. In this retrospective single centric study, 512 patients who underwent LT for HCC were divided into four groups according to cumulative exposure to tacrolimus (CET) during 3 months after LT: conventional (n = 218), aggressive minimization (n = 32), minimization (n = 161), and high exposure (n = 101). Impact of CET on HCC recurrence and death were analyzed. Compared with the conventional group, the other three CET groups showed a similar risk of HCC recurrence. The aggressive minimization group showed a higher risk [hazard ratio (HR) 5.64, P < 0.001] and the high exposure group showed a marginal risk (HR 1.67, P = 0.081) of overall death compared to the conventional group. CET during 3 months was not associated with HCC recurrence in the matched cohort and various subgroups. TAC minimization is not effective to prevent HCC recurrence but could result in higher mortality in LT recipients.

Utility of preoperative troponin I to predict mortality in adult liver transplant recipients: Revisiting pretransplant cardiac risk in the current MELD-allocation era.

Preoperative risk assessment in liver transplant (LT) candidates, particularly related to cardiac risk, is an area of intense interest for transplant clinicians. Various cardiac testing methods are employed by transplant centers to characterize cardiac risk. Serum troponin is an established method for the detection of myocardial injury in a wide variety of clinical settings. Preoperative troponin screening has been reported to predict postoperative cardiac events and mortality in various surgical patient populations, however, the utility of preoperative troponin to predict posttransplant outcomes in current LT candidate populations requires further investigation. We performed a prospective blinded study in a cohort of 275 consecutive LT recipients at a single transplant center to determine if preoperative serum troponin I (TnI) was predictive for postoperative 1-year mortality. Abnormal preoperative TnI levels (>.1ng/mL) were found in 38 patients (14%). One-year mortality occurred in 19 patients (7%). There was no significant difference in mortality between patients with normal and abnormal troponin levels. Additionally, we found that there was no significant difference in early postoperative major adverse cardiac events between patient groups. Contrary to previous reports, elevated preoperative TnI was not significantly predictive of posttransplant mortality in LT recipients at our institution.

S1441 Serum Fibrosis and Steatosis Biomarkers for the Prediction of Mortality in Liver Transplant Recipients

S1441 Serum Fibrosis and Steatosis Biomarkers for the Prediction of Mortality in Liver Transplant Recipients

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality.

Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation. To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA). In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group. The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero). In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

Impact of preoperative red blood cell transfusion on long-term mortality of liver transplantation: A retrospective cohort study.

Preoperative red blood cell (RBC) transfusion can induce immune modulation and alloimmunization; however, few studies have investigated the effect of preoperative transfusion and hemoglobin levels that need to be corrected before surgery, especially in critically ill patients such as those with end-stage liver disease who undergo liver transplantation (LT). This study aimed to investigate the effects of preoperative RBC transfusion on long-term mortality in LT recipients. A total of 249 patients who underwent LT at a single center between January 2012 and December 2021 were included in this study. The patients were divided into 2 groups: preoperative transfusion and preoperative non-transfusion. Since the baseline characteristics were significantly different between the 2 groups, we performed propensity score matching, including factors such as the Model for End-Stage Liver Disease score and intraoperative RBC transfusion, to exclude possible biases that could affect prognosis. We analyzed the 5-year mortality rate as the primary outcome. The preoperative transfusion group showed a 4.84-fold higher hazard ratio than that in the preoperative non-transfusion group. There were no differences in 30-day mortality, duration of intensive care unit stay, or graft rejection rate between the 2 groups. Preoperative transfusion could influence long-term mortality in LT, and clinicians should pay attention to RBC transfusion before LT unless the patient is hemodynamically unstable. A large-scale randomized controlled trial is needed to determine the possible mechanisms related to preoperative RBC transfusion, long-term mortality, and the level of anemia that should be corrected before surgery.

Causes of death and associated factors with death after liver transplantation: a nationwide database study

Background/aimsThis study investigated overall, 1-year, and 5-year mortality rate, the causes of death, and associated factors with death in liver transplantation recipients. MethodsA total of 11,590 liver transplant recipients identified from National Health Insurance Service database between 2006 and 2017 were included. Factors associated with all-cause of death were analyzed by Cox proportional regression models. Cumulative mortality rate according to the underlying indication was estimated by Kaplan–Meier method. ResultsThe 12-year survival rate for all liver transplant recipients was 68%. In the overall, 1-year, and 5-year mortality of liver transplant recipients, hepatic death was the highest contributing risk, accounting for >65% of the causes of death. Deaths from cirrhosis and liver failure accounted for a high proportion of deaths within 1 year after transplantation, and deaths from malignant tumors such as hepatocellular carcinoma were high among late-stage deaths. DiscussionAlthough the most common cause of death from liver transplantation is due to primary disease, there was a difference in the pattern of major causes of death according to the period from transplantation to death. If appropriate medical intervention is performed at each period after transplantation, the survival rate can be improved.

Cytomegalovirus Disease as a Risk Factor for Invasive Fungal Infections in Liver Transplant Recipients under Targeted Antiviral and Antimycotic Prophylaxis.

We retrospectively analyzed the medical records of 214 adult liver transplant recipients (LTRs). Universal antiviral prophylaxis was utilized in recipients with CMV mismatch; intermediate- and low-risk patients received pre-emptive treatment. Six percent of patients developed CMV disease independent of their serostatus. The occurrence of CMV disease was associated with elevated virus load and increased incidence of leucopenia and IFIs. Furthermore, CMV disease was associated with higher one-year mortality and increased relapse rates within the first year of OLT. CMV disease causes significant morbidity and mortality in LTRs, directly affecting transplant outcomes. Due to the increased risk of IFIs, antifungal prophylaxis for CMV disease may be appropriate. Postoperative CMV monitoring should be considered after massive transfusion, even in low-risk serostatus constellations. In case of biliary complications, biliary CMV monitoring may be appropriate in the case of CMV-DNA blood-negative patients.

Effect of COVID-19 Pandemic on Patients Who Have Undergone Liver Transplantation: Retrospective Cohort Study.

In liver transplant (LT) recipients, immunosuppressive therapy may potentially increase the risk of severe COVID-19 and may increase the mortality in patients. However, studies have shown conflicting results, with various studies reporting poor outcomes while the others show no difference between the LT recipients and healthy population. The aim of this study is to determine the impact of the COVID-19 pandemic on survival of LT recipients. This is a retrospective cohort study analyzing the data from 387 LT recipients diagnosed with COVID-19. LT recipients were divided into two groups: survival (n = 359) and non-survival (n = 28) groups. A logistic regression model was used to determine the independent risk factors for mortality. Machine learning models were used to analyze the contribution of independent variables to the mortality in LT recipients. The COVID-19-related mortality rate in LT recipients was 7.2%. Multivariate analysis showed that everolimus use (p = 0.012; OR = 6.2), need for intubation (p = 0.001; OR = 38.4) and discontinuation of immunosuppressive therapy (p = 0.047; OR = 7.3) were independent risk factors for mortality. Furthermore, COVID-19 vaccination reduced the risk of mortality by 100 fold and was the single independent factor determining the survival of the LT recipients. The effect of COVID-19 infection on LT recipients is slightly different from the effect of the disease on the general population. The COVID-19-related mortality is lower than the general population and vaccination for COVID-19 significantly reduces the risk of mortality.

Effect of Pretransplant Sarcopenia on Mortality in Liver Transplant Recipients

Sarcopenia is an important metabolic disorder associated with end-stage liver disease and is an independent predictor of mortality in liver transplant candidates. We evaluated effects of pretransplant muscle mass, muscle quality, and visceral adipose tissue on mortality after liver transplant. For 2015-2020, we included 65 liver transplant recipients whose records contained pretransplant liver computed tomography images. We calculated skeletal muscle mass index (muscle tissue area in centimeters squared divided by height in meters squared), visceral-to-subcutaneous fat ratio (visceral adiposity indicator), and intramuscular adipose tissue content ratio (muscle quality indicator). Median age was 55 years (IQR, 45-63 years), and 48 (73.8%) patients were men. During follow-up, 53 (81.5%) study group patients survived; mean survival time was 71.73 ± 3.81 months. The deceased patient group had a statistically higher pretransplant visceral-to-subcutaneous fat ratio than the survival group (P = .046). Survival was 100% for 1 positive indicator, 86.2% for 2 positive indicators, and 70.4% for 3 positive indicators (P = .096). Positive correlation was confirmed between pretransplant skeletal muscle mass index and age (P = .043) and pretransplant body mass index (weight in kilograms divided by height in meters squared) (P < .001). There was a moderate positive correlation between pretransplant intramuscular adipose tissue content ratio and age (R = 0.529, P ≤ .001) and a weak positive correlation with pretransplant body mass index (R = 0.361, P = .003). Furthermore, pretransplant visceral- tosubcutaneous fat ratio showed a weak positive correlation with age (R = 0.306, P = .013) and a weak negative correlation with the Model for End-Stage Liver Disease score (R = -0.301, P = .016). Pretransplant sarcopenia is an important indicator to predict mortality and morbidity in posttransplant follow-up. Visceral-to-subcutaneous fat ratio is an important parameter to evaluate sarcopenia in liver transplant patients.

SARS-CoV-2 vaccine alleviates disease burden and severity in liver transplant recipients even with low antibody titers.

We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

Albuminuria post-liver transplant is a predictor of kidney disease progression and mortality.

BACKGROUND: Albuminuria is a marker of chronic kidney disease (CKD) associated with an increased risk of end-stage kidney disease (ESKD) and mortality in the general population, but it is uncertain whether the same association exists in liver transplant (LT) recipients. This study examined the association between albuminuria and kidney failure and mortality in LT recipients.METHODS: Retrospective cohort study of 294 adults who received a LT between January 1, 1989, and December 31, 2011, in British Columbia, Canada. Cox multivariable regression was used to determine the association between ACR and a primary combined outcome of mortality, doubling of serum creatinine, or ESKD; and a secondary outcome of a decrease in estimated glomerular filtration rate (eGFR) ≥30%. RESULTS: At baseline, mean eGFR was 67 (SD 20.9) mL/min/1.73 m2, and 10% had severe albuminuria (ACR >30 mg/mmol). The primary outcome occurred in 20.4% (60) of patients and was associated with ACR >30 mg/mmol (HR 2.77, 95% CI 1.28-6.04; P = 0.01). A decline in eGFR ≥30% occurred in 21.8% (64) of patients, and was associated with ACR >30 mg/mmol (HR 4.77, 95% CI 2.31-9.86; P < 0.0001). CONCLUSIONS: Severe albuminuria (ACR >30 mg/mmol) was associated with an increased risk of loss of kidney function and mortality after LT. Prospective studies are needed to determine if specific interventions directed at reducing albuminuria can improve long-term outcomes in LT recipients.

Interpretable prediction of mortality in liver transplant recipients based on machine learning

Background:Accurate prediction of the mortality of post-liver transplantation is an important but challenging task. It relates to optimizing organ allocation and estimating the risk of possible dysfunction. Existing risk scoring models, such as the Balance of Risk (BAR) score and the Survival Outcomes Following Liver Transplantation (SOFT) score, do not predict the mortality of post-liver transplantation with sufficient accuracy. In this study, we evaluate the performance of machine learning models and establish an explainable machine learning model for predicting mortality in liver transplant recipients. Method:The optimal feature set for the prediction of the mortality was selected by a wrapper method based on binary particle swarm optimization (BPSO). With the selected optimal feature set, seven machine learning models were applied to predict mortality over different time windows. The best-performing model was used to predict mortality through a comprehensive comparison and evaluation. An interpretable approach based on machine learning and SHapley Additive exPlanations (SHAP) is used to explicitly explain the model’s decision and make new discoveries. Results:With regard to predictive power, our results demonstrated that the feature set selected by BPSO outperformed both the feature set in the existing risk score model (BAR score, SOFT score) and the feature set processed by principal component analysis (PCA). The best-performing model, extreme gradient boosting (XGBoost), was found to improve the Area Under a Curve (AUC) values for mortality prediction by 6.7%, 11.6%, and 17.4% at 3 months, 3 years, and 10 years, respectively, compared to the SOFT score. The main predictors of mortality and their impact were discussed for different age groups and different follow-up periods. Conclusions:Our analysis demonstrates that XGBoost can be an ideal method to assess the mortality risk in liver transplantation. In combination with the SHAP approach, the proposed framework provides a more intuitive and comprehensive interpretation of the predictive model, thereby allowing the clinician to better understand the decision-making process of the model and the impact of factors associated with mortality risk in liver transplantation.

P9.05: Biliary Complications Following Liver Transplantation: A 13-Years Single-Center Experience

Introduction: Orthotopic liver transplantation (LT) is the chosen treatment for end-stage liver disease. Despite the advances in the surgical techniques, biliary tract complications are the most common problems seen after transplantation with an incidence range of 10-25%. We aim to describe the incidence of biliary complications at our center. Patients and Methods: Retrospective study of patients who suffered from biliary complications after LT between September 2009 and February 2022 in a single center. Demographic characteristics: cause of liver failure, MELD score, time on waiting list (WL), DRI, national, regional or local procurement; preservation solution, warm ischemia time (WIT), cold ischemia time (CIT), chosen treatment and success rate (SR), patient and graft survival. Biliary complications were divided into 2 groups, according to the moment of appearance: early complication (EC) when they happened within the first 30 post-operative days and delayed complication (DC) when they ocurred afterwards. All analyses were performed using IBM SPSS v25.0. Results: From a total of 549 LT that were performed during the period of study, 90 (16%) had biliary tract complications. Among them, 78 were adult recipients, with a mean age of 48 years old (DS 21). Sixty-four transplants (71%) were performed due to cirrhosis, caused mainly due to viral disease (25, 39%) and alcohol (18, 28%). Sixty-nine (90%) were performed with whole liver and 8 (10%) with partial grafts (7 right and 1 left lobe). The most frequent biliary complication in the EC and DC group was the biliary anastomotic stenosis, with 21 (60%) and 33 cases (78%), respectively. Eighteen patients (23%) lost their graft (7 EC and 11 DC). Table 1 shows biliary complications according to time of appearance and initial treatment chosen.Among the pediatric patients, the mean age was 3 years old (range 1-10) and the main cause for transplant was biliary atresia (5, 42%). Nine patients suffered of biliary leak (8 within the EC groups and 1 DC) and 3 of biliary anastomotic stenosis (2 EC and 1 DC). Three patients (25%) lost their grafts (all from EC). Table 2 shows biliary complications according to time of appearance and initial treatment chosen.Discussion: Biliary complications remain a major cause of morbidity, dysfunction, and mortality in liver transplant recipients and continue to be a challenging aspect in the management of such patients. With appropriate management, however, there impact on graft and overall survival could be minimized.

Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcome?

Metabolic syndrome (MS) and cardiovascular risk factors are common in liver transplant (LT) candidates and recipients. Cardiovascular events and de novo tumors are increasingly common causes of mortality in liver transplant recipients. The aim of this study were (i) assess the prevalence of MS in LT recipients and its growth over the years and (ii) determine if the presence of MS pre-LT is associated with a higher risk of post-LT cardiovascular events (CVE), de novo tumors or early and late survival. A retrospective study was performed that included LT recipients from January 2012 to December 2017. Baseline features (MS before LT and at 1year post-LT) and outcomes (CVE, de novo tumors and survival) were recorded. 483 recipients were included, MS was present in 20% of pre-LT with an increasing prevalence over time, from 16% in 2012 to 34% in 2017 (p=0.025). One-year post-LT, an additional 12% had developed de novo MS. At a median of 56-months follow-up, 13% developed a CVE and 9% a de novo tumor. One and 5-yr survival rates were 91% and 83% in those with pre-LT MS and 93% and 85% in those without (p=0.94).The presence of MS before LT was independently associated with a higher risk of post-LT CVE (HR: 2.66 IC (95%): 1.6-4.4 p< 0.001), but not with de novo tumors (p=0.94) nor early and late survival (p=0.58 and p=0.87). Pre-LT MS is increasing among LT candidates and is associated with a higher risk of post-LT morbidity CVE yet without affecting mortality. .

Personalizing Diabetes Management in Liver Transplant Recipients: The New Era for Optimizing Risk Management.

Post‐transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post‐transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co‐existing conditions. Sodium‐glucose co‐transporter 2 inhibitors and glucagon‐like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR‐specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra‐glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long‐term management based on risk factors and co‐morbidities.

Blood Pressure Variability Early After Liver Transplantation Predicts Long-Term Mortality.

Cardiovascular disease is a leading cause of mortality after liver transplantation (LT). Elevated blood pressure (BP) in LT recipients (LTRs) is associated with increased cardiovascular events (CVEs) and decreased survival. Increased visit-to-visit BP variability in the general population is associated with adverse outcomes. Whether BP variability is associated with adverse outcomes in LTRs is unknown. We analyzed data from adult LTRs within a single large transplant center in the United States between 2010 and 2016. Day-to-day BPvariability within the first 60 days after LT was measured usingvariability independent of the mean (VIM). To assess the association between early post-LT BP variability and future CVEs or mortality, we used Cox proportional hazard regression. Among 512 LTRs (34.4% women; 10.7% Black; mean age, 56.5 years), increased systolic BP (SBP) variability was associated with a decreased risk of mortality (adjusted hazard ratio [aHR], 0.97/1 unit VIM; 95% confidence interval [CI], 0.94-0.99). This was particularly true for men (aHR, 0.94; 95% CI, 0.91-0.98), patients with pre-LT atherosclerotic cardiovascular disease (aHR, 0.95; 95% CI, 0.92-0.98), and patients without pre-LT diabetes mellitus (aHR, 0.96; 95% CI, 0.93-1.00). There was no significant effect of BP variability on CVEs. Results were consistent when competing risk analysis was used with death as the competing risk. Increased diastolic BP variability was not associated with a significant effect on CVEs (hazard ratio [HR], 0.96; 95% CI, 0.90-1.02) nor mortality (HR, 1.00; 95% CI, 0.95-1.06). Increased SBP variability, independent of mean BP, is associated with decreased mortality in LTRs. We postulate that increased BP variability reflects a better vascular recovery in patients undergoing LT, but further research is needed as to the mechanism underlying our observation.