Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors

BACKGROUND Hepatic artery occlusion(HAO)after liver transplantation(LT)is a devastating complication,resulting in early graft loss and reduced overall survival.Ultra-sound is an established assessment method for HAO in patients following LT,especially those with complex hepatic artery reconstruction.METHODS We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022.Fourteen patients diagnosed with acute HAO(A-HAO)by surgery and fifteen diagnosed with chronic HAO(C-HAO)were included.A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table.All patients underwent an ultrasono-graphy examination.Parameters including resistance index(RI),peak systolic velocity(PSV),and portal vein velocity(PVV)were compared across the groups.Additionally,basic clinical data were collected for all patients,including gender,age,primary diagnosis,D-dimer concentration,total operation time,cold ischemia time,hot ischemia time,intraoperative blood loss and transfusion,intraoperative urine volume,infusion,model for end-stage liver disease(MELD)score,and whether complex hepatic artery reconstructions were performed.Furthermore,risk factors influencing HAO formation after LT were analyzed.RESULTS Compared to the non-HAO group,PVV and RI were higher in the A-HAO group,while PSV was lower.Conversely,both PSV and RI were lower in the C-HAO group compared to the non-HAO group.The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase(GGT)level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group.However,there were no distinct differences between the two groups in D-dimer,MELD score,pre-occlusion alanine transaminase and aspartate transaminase levels,or intraoperative conditions.CONCLUSION Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development.Additionally,complex hepatic artery reconstructions,defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries,constitute a risk factor for A-HAO.Besides,abnormal pre-occlusion GGT elevation is an important biochemical indicator.Therefore,ultrasound examination serves as an important tool for screening HAO,especially in patients with the identified risk factors.

Biliary complications following liver transplantation: Singlecenter experience over three decades and recent risk factors

AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.METHODS A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease(MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logisticregression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate. RESULTS Biliary complications were observed in 227 cases(14.1%). Four hundred and seventeen(26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21%(n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46%(n = 41)], anastomotic strictures [25%(n = 22)], cholangitis [8%(n = 7)] and non-anastomotic strictures [3%(n = 3)]. The remaining 18%(n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation(P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively(P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation(P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702.CONCLUSION The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.

Plasma levels of tumor necrotic factor-alpha and interleukin-6, -8 during orthotopic liver transplantation and their relations to postoperative pulmonary complications

BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.

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

BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS 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.RESULTS 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,posttransplant 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).CONCLUSION 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.

Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis

AIM: To determine the risk factors for new-onset diabetes mellitus(NODM) after liver transplantation by conducting a systematic review and meta-analysis.METHODS: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the Rev Man5.0 software(The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios(OR) or weighted mean differences(WMD) with 95% confidence intervals(CIs) were calculated using either a fixed effects or a random effects model, based on the presence(I2 < 50%) or absence(I2 > 50%) of significant heterogeneity. RESULTS: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus(HCV) infection(OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes(OR = 1.69, 95%CI: 1.09-2.63, P < 0.00001); male gender(OR = 1.53; 95%CI: 1.24-1.90; P < 0.0001); impaired fasting glucose(IFG; OR = 3.27; 95%CI: 1.84-5.81; P < 0.0001); a family history of diabetes(OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus(OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index(BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P < 0.00001). Other factors, such as hepatitis B virus infection and alcoholism, were not found to be associated with the incidence of NODM.CONCLUSION: The study showed that HCV infection, IFG, a family history of diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.

Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.

Risk factors associated with early and late HAT after adult liver transplantation

AIM: To identify risk factors that might contribute to hepatic artery thrombosis (HAT) after liver transplantation (LT). METHODS: The perioperative and follow-up data of a total of 744 liver transplants, performed from February 1999 to July 2010, were retrospectively reviewed. HAT developed in 20 patients (2.7%). HAT was classified as early (occurring in fewer than 30 d post LT) or late (occurring more than 30 d post LT). Early HAT devel-oped in 14 patients (1.9%). Late HAT developed in 6 patients (0.8%). Risk factors associated with HAT were analysed using the chi(2) test for univariate analysis and logistic regression for multivariate analysis. RESULTS: Lack of ABO compatibility, recipient/donor weight ratio >= 1.15, complex arterial reconstruction, duration time of hepatic artery anastomosis > 80 min, duration time of operation > 10 h, dual grafts, number of units of blood received intraoperatively >= 7, number of units of fresh frozen plasma (FFP) received intraoperatively >= 6, postoperative blood transfusion and postoperative FFP use were significantly associated with early HAT in the univariate analysis (P < 0.1). After logistic regression, independent risk factors associated with early HAT were recipient/donor weight ratio >= 1.15 (OR = 4.499), duration of hepatic artery anastomosis > 80 min (OR = 5.429), number of units of blood received intraoperatively >= 7 (OR = 4.059) and postoperative blood transfusion (OR = 6.898). Graft type (whole/living-donor/split), duration of operation > 10 h, retransplantation, rejection reaction, recipients with diabetes preoperatively and recipients with a high level of blood glucose or diabetes postoperatively were significantly associated with late HAT in the univariate analysis (P < 0.1). After logistic regression, the independent risk factors associated with early HAT were duration of operation > 10 h (OR = 6.394), retransplantation (OR = 21.793) and rejection reactions (OR = 16.936). CONCLUSION: Early detection of these risk factors, strict surveillance protocols by Doppler ultrasound and prophylactic anticoagulation for recipients at risk might be determined prospectively. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Risk factors of metabolic syndrome after liver transplantation

BACKGROUND： Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients.

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

AIM： To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation （OLT）. METHODS： Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system （MARS） as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality （30 d） after OLT. RESULTS： In the 50 patients, the statistically significant improvement in the biochemical parameters was observed （pre-treatment and post-treatment）. Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was： 28 kept alive and 6 patients died. CONCLUSION： Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

Incidence and risk factors for early renal dysfunction after liver transplantation

AIM: To determine renal dysfunction post liver transplantation, its incidence and risk factors in patients from a Belgian University Hospital.METHODS: Orthotopic liver transplantations performed from January 2006 until September 2012 were retrospectively reviewed(n = 187). Patients with no renal replacement therapy(RRT) before transplantation were classified into four groups according to their highest creatinine plasma level during the first postoperative week. The first group had a peak creatinine level below 12 mg/L, the second group between 12 and 20 mg/L, the third group between 20 and 35 mg/L, and the fourth above 35 mg/L. In addition, patients who needed RRT during the first week after transplantation were also classified into the fourth group. Perioperative parameters were recorded as risk factors, namely age, sex, bodymass index(BMI), length of preoperative hospital stay, prior bacterial infection within one month, preoperative ascites, preoperative treatment with β-blocker, angiotensin-converting enzyme inhibitor or non steroidal anti-inflammatory drugs, preoperative creatinine and bilirubin levels, donor status(cardiac death or brain death), postoperative lactate level, need for intraoperative vasopressive drugs, surgical revision, mechanical ventilation for more than 24 h, postoperative bilirubin and transaminase peak levels, postoperative hemoglobin level, amount of perioperative blood transfusions and type of immunosuppression. Univariate and multivariate analysis were performed using logistic ordinal regression method. Post hoc analysis of the hemostatic agent used was also done.RESULTS: There were 78 patients in group 1(41.7%), 46 in group 2(24.6%), 38 in group 3(20.3%) and 25 in group 4(13.4%). Twenty patients required RRT: 13(7%) during the first week after transplantation. Using univariate analysis, the severity of renal dysfunction was correlated with presence of ascites and prior bacterial infection, preoperative bilirubin, urea and creatinine level, need for surgical revision, use of vasopressor, postoperative mechanical ventilation, postoperative bilirubin and urea, aspartate aminotransferase(ASAT), and hemoglobin levels and the need for transfusion. The multivariate analysis showed that BMI(OR = 1.1, P = 0.004), preoperative creatinine level(OR = 11.1, P < 0.0001), use of vasopressor(OR = 3.31, P = 0.0002), maximal postoperative bilirubin level(OR = 1.44, P = 0.044) and minimal postoperative hemoglobin level(OR = 0.059, P = 0.0005) were independent predictors of early post-liver transplantation renal dysfunction. Neither donor status nor ASAT levels had significant impact on early postoperative renal dysfunction in multivariate analysis. Absence of renal dysfunction(group 1) was also predicted by the intraoperative hemostatic agent used, independently of the extent of bleeding and of the preoperative creatinine level.CONCLUSION: More than half of receivers experienced some degree of early renal dysfunction after liver transplantation. Main predictors were preoperative renal dysfunction, postoperative anemia and vasopressor requirement.

Perioperative thrombotic complications in liver transplantation

Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival.Thromboembolism during OLT is characterized not only by a complex aetiology,but also by unpredictable onset and evolution of the disease.The initiation of a procoagulant process may be triggered by various factors,such as inflammation,venous stasis,ischemia-reperfusion injury,vascular clamping,anatomical and technical abnormalities,genetic factors,deficiency of profibrinolytic activity,and platelet activation.The involvement of the arterial system,intracardiac thrombosis,pulmonary emboli,portal vein thrombosis,and deep vein thrombosis,are among the most serious thrombotic events in the perioperative period.The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis,particularly when these events occur intraoperatively or early after OLT.Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting,many institutions recommend such an approach especially in the subset of patients at high risk.However,the decision of when,how and in what doses to use the various chemical anticoagulants is still a difficult task,since there is no common consensus,even for highrisk cases.The risk of postoperative thromboembolism causing severe hemodynamic events,or even loss of graft function,must be weighed and compared with the risk of an important bleeding.In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurringin the perioperative period,as well as their incidence and clinical features.Moreover,the indications to pharmacological prophylaxis and the current treatment strategies are also summarized.

Biliary complications in recipients of living donor liver transplantation:A single-centre study

BACKGROUND Biliary complications(BCs)after liver transplantation(LT)remain a considerable cause of morbidity,mortality,increased cost,and graft loss.AIM To investigate the impact of BCs on chronic graft rejection,graft failure and mortality.METHODS From 2011 to 2016,215 adult recipients underwent right-lobe living-donor liver transplantation(RT-LDLT)at our centre.We excluded 46 recipients who met the exclusion criteria,and 169 recipients were included in the final analysis.Donors’and recipients’demographic data,clinical data,operative details and postoperative course information were collected.We also reviewed the management and outcomes of BCs.Recipients were followed for at least 12 mo post-LT until December 2017 or graft or patient loss.RESULTS The overall incidence rate of BCs including biliary leakage,biliary infection and biliary stricture was 57.4%.Twenty-seven(16%)patients experienced chronic graft rejection.Graft failure developed in 20(11.8%)patients.A total of 28(16.6%)deaths occurred during follow-up.BCs were a risk factor for the occurrence of chronic graft rejection and failure;however,mortality was determined by recurrent hepatitis C virus infection.CONCLUSION Biliary complications after RT-LDLT represent an independent risk factor for chronic graft rejection and graft failure;nonetheless,effective management of these complications can improve patient and graft survival.

Comment on pediatric living donor liver transplantation decade progress in Shanghai: Characteristics and risks factors of mortality

Since the first successful liver transplantation was performed five decades ago,pediatric liver transplantation has become the gold standard treatment choice for pediatric liver disease,including metabolic diseases,liver tumors,and some acute liver failure.With improvements in immunosuppression,surgical techniques,and postoperative medical care,long-term outcomes of patients after liver transplantation have markedly improved,especially in pediatric patients.

Latent tuberculosis:Risk factors,screening and treatment in liver transplantation recipients from an endemic area

BACKGROUND Patients undergoing solid organ transplantation,particularly those who live or have lived in tuberculosis(TB)endemic areas,are at a high risk of developing TB.The majority of post-transplantation TB cases are associated with reactivation of latent TB infection(LTBI).Brazil is in a single position with overlapping areas of high TB endemicity and high transplant activity.In liver transplant(LT),one should be aware of the potential hepatotoxicity associated with the treatment regimens for LTBI.AIM To evaluate the frequency of LTBI in LT patients and treatment-related issues.METHODS This was a retrospective analysis of a cohort of cirrhotic patients aged≥18 years,who underwent LT at a high-complexity teaching hospital from January 2005 to December 2012.RESULTS Overall,429 patients underwent LT during the study period.Of these,213(49.7%)underwent the tuberculin skin test(TST)during the pre-transplant period,and 35(16.4%)of them had a positive result.The treatment for LTBI was initiated after LT in 12(34.3%)of the TST-positive patients;in 3(25.0%),treatment was maintained for at least 6 mo.CONCLUSION The prevalence of LTBI was lower than expected.Initiation and completion of LTBI treatment was limited by difficulties in the management of these special patients.

Cardiac risk factors limiting survival to liver transplantation in patients with nonalcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)describes the hepatic manifestations of metabolic syndrome,which is estimated to affect 25%of adults,and currently represents the second most common indication for liver transplant in the United States.Studies have shown that patients with NAFLD are at an increased risk for heart failure,arrhythmia,and coronary artery disease(CAD),which may impact outcomes of liver transplantation.However,it remains unclear whether the presence of cardiac disease affects survival prior to liver transplant.If so,this would represent an important opportunity to optimize cardiac status and improve outcomes before liver transplant.AIM To identify cardiac factors that impact survival to liver transplantation in patients with NAFLD and on the transplant waitlist.METHODS The aim of this study was to identify cardiac risk factors that limit survival to transplant in patients with NAFLD.We performed a retrospective analysis of patients with NAFLD listed for liver transplant at a tertiary academic medical center in the United States from January 2015 to January 2021,identified through United Network of Organ Sharing registry.Exclusion criteria included a concurrent etiology of liver disease and removal from the transplant list due to chemical dependency,lack of social support,improvement in liver disease,or being lost to followup.We manually reviewed patient charts including electrocardiogram,echocardiogram,and cardiac catheterization reports as well as physician notes to identify cardiac disease states(i.e.,heart failure,arrhythmia,valvular disease and CAD)and other related diagnoses.We performed a survival analysis by Cox proportional hazards regression model to analyze the association between cardiac factors at the time listed for transplant and death or clinical deterioration prior to transplant.RESULTS Between January 2015 and January 2021,265 patients with nonalcoholic fatty liver disease were listed for liver transplant at our institution.Our patient sample had a median age of 63 and an even distribution between sexes.The median Model for End-Stage Liver Disease(MELD)score was 17 and the median body mass index was 31.6.Of these 265 patients,197(74.3%)survived to transplant and 68(25.7%)died or clinically deteriorated prior to transplant.The presence of mild or moderate CAD represented a hazard ratio of 2.013(95%CI 1.078-3.759,P=0.029)for death or clinical deterioration when compared to patients without CAD,after adjustment for age,sex,and MELD.MELD represented an adjusted hazard ratio of 1.188.CONCLUSION Mild or moderate CAD represents a hazard for waitlist mortality prior to liver transplant in patients with NAFLD.Aggressive management of CAD may be needed to improve patient outcomes.

Is low postoperative cholesterol level really an independent risk factor of adverse outcomes after living donor liver transplantation?

To the Editor:We read with great interest the article by Yang et al.[1]evaluating the effects of postoperative serum total cholesterol(s TC)changes on early allograft dysfunction and survival after living donor liver transplantation(LDLT).By the multivariate regression analysis,they showed that patients with s TC<1.42 mmol/L on postoperative day 3 had 4.08-fold and 2.72-fold greater risks of

Metabolic complications in liver transplant recipients

The metabolic syndrome(MS), which includes obesity,dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease(CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease(NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.

Prophylactic liver transplantation for high-risk recurrent hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. Radical treatment of HCC in early stages results in a long disease-free period and improved overall survival. The choice of optimal management strategy for HCC mainly depends on the severity of the underlying liver disease. For patients with decompensated liver cirrhosis and HCC within Milan criteria (MC), liver transplant (LT) is the choice of treatment. However, for patients with good residual liver reserve and HCC within MC, selection of other curative treatments such as liver resection (LR) or radiofrequency ablation may be a reasonable alternative. For patients without cirrhosis, LR can result in an overall survival similar to that provided by LT. Therefore, it is an accepted alternative to LT especially in areas with organ shortage. However, the cumulative 5-year recurrence rate of HCC post LR might be as high as 70%. For initial transplant-eligible (within MC) patients with recurrent HCC post LR, salvage liver transplant (SLT) was first proposed in 2000. However, most patients with recurrent HCC considered for SLT are untransplantable cases due to HCC recurrence beyond MC or comorbidity. Thus, the strategy of opting for SLT results in the loss of the opportunity of LT for these patients. Some authors proposed the concept of &ldquo;de principe liver transplant&rdquo; (i.e., prophylactic LT before HCC recurrence) to prevent losing the chance of LT for these potential candidates. Factors associated with the failure of SLT will be dissected and discussed in three parts: Patient, tumor, and underlying liver disease. Regarding patient-related factors, the rate of transplantability depends on patient compliance. Patients without regular follow-up tend to develop HCC recurrence beyond MC at the time of tumor detection. Advancing age is another factor related to severe comorbidities when LT is considered for HCC recurrence, and these elderly candidates become ineligible as time goes by. Regarding tumor-related factors, histopathological features of the resected specimen are used mostly for determining the prognosis of early HCC recurrences. Such prognostic factors include the presence of microvascular invasion, poor tumor differentiation, the presence of microsatellites, the presence of multiple tumors, and the presence of the gene-expressing signature associated with aggressive HCC. These prognostic factors might be used as a selection tool for SLT or prophylactic LT, while remaining mindful of the fact that most of them are also prognostic factors for post-transplant HCC recurrence. Regarding underlying liver disease-related factors, progression of chronic viral hepatitis and high viral load may contribute to the development of late (de novo) HCC recurrence as a consequence of sustained inflammatory reaction. However, correlation between the severity of liver fibrosis and tumor recurrence is still controversial. Some prognostic scoring systems that integrate these three factors have been proposed to predict recurrence patterns after LR for HCC. Theoretically, after excluding patients with high risk of post-transplant HCC recurrence, either by observation of a cancer-free period or by measurement of biological factors (such as alpha fetoprotein), prophylactic LT following curative resection of HCC could be considered for selected patients with high risk of recurrence to provide longer survival.

Liver transplantation for hepatocellular carcinoma- factors influencing outcome and disease-free survival

Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.