Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Prognostic value of ultrasound in early arterial complications post liver transplant

Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study

BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.AIM To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients,mainly early allograft dysfunction.METHODS This multicenter retrospective study included brain-dead donors and adult liver graft recipients.Donor-recipient matching was obtained through a crossover list.Clinical and laboratory data were recorded for both donors and recipients.Donor hepatectomy,cold ischemia,and warm ischemia times were recorded.Primary outcome was early allograft dysfunction.Secondary outcomes included need for retransplantation,length of intensive care unit and hospital stay,and patient and graft survival at 12 months.RESULTS From January 2019 to December 2021,a total of 243 patients underwent a liver transplant from a brain-dead donor.Of these,57(25%)developed early allograft dysfunction.The median donor hepatectomy time was 29(23–40)min.Patients with early allograft dysfunction had a median hepatectomy time of 25(22–38)min,whereas those without it had a median time of 30(24–40)min(P=0.126).CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction,graft survival,or patient survival following liver transplantation.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities

BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)patients required re-transplantation.Most patients received a living-related liver graft(82%).Pediatric patients received more living and related grafts than adults(P=0.038 and P=0.041,respectively),while adult patients received more cadaveric and unrelated grafts.Most patients required long-term immunosuppressive therapy after LT(94.7%),of which tacrolimus was the most prescribed(84.0%),followed by prednisolone(50.7%),which was prescribed more frequently for pediatric patients(P=0.001).Most patients developed complications(62.4%)with infectious episodes being the most common(38.9%),followed by biliary stricture(19.5%).Tonsilitis and sepsis(n=12,8.1%for each)were the most frequent infections.Pediatric patients experienced higher rates of infection,rejection,and early poor graft function than adult patients(P<0.001,P=0.003,and P=0.025,respectively).The median follow-up time was 6.5(IQR:2.6–10.6)years.The overall survival rate was 84.4%,the 5-year survival rate,86.2%,and the mortality rate,15.6%.Younger patients had significantly better odds of survival(P=0.019)and patients who survived had significantly longer follow-up periods(P<0.001).CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries.Since LT facilities are not available,an overseas LT has offered them great hope.

Sarcopenia in cirrhotic patients: Does frailty matter while waiting for a liver transplant?

Sarcopenia reflects patient frailty and should be routinely assessed due to its high prevalence in cirrhotic patients awaiting liver transplants.Pre-transplant nutritional optimization should be tailored for patients with a definitive diagnosis of sarcopenia,therefore improving functional status at transplant and reducing posttransplant mortality.Hepatologists and transplant surgeons should have raised awareness regarding sarcopenia and the reflected frailty that hinder posttransplant outcomes.The policymakers should also take into account when modifying the organ allocation model that sarcopenia or frailty might become a decisive factor in allocating organs for cirrhotic patients,in order to ensure post-transplant survival and quality of life.

Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study

BACKGROUND The growing disparity between the rising demand for liver transplantation(LT)and the limited availability of donor organs has prompted a greater reliance on older liver grafts.Traditionally,utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors.By accounting for additional risk factors,we hypothesize that the utili-zation of older liver grafts has a relatively minor impact on both patient survival and graft viability.AIM To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups.METHODS In the period from April 2013 to December 2018,656 adult liver transplants were performed at the University Hospital Merkur.Several multivariate Cox propor-tional hazards models were developed to independently assess the significance of donor age.Donor age was treated as a continuous variable.The approach involved univariate and multivariate analysis,including variable selection and assessment of interactions and transformations.Additionally,to exemplify the similarity of using young and old donor liver grafts,the group of 87 recipients of elderly donor liver grafts(≥75 years)was compared to a group of 124 recipients of young liver grafts(≤45 years)from the dataset.Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups.RESULTS Using multivariate Cox analysis,we found no statistical significance in the role of donor age within the constructed models.Even when retained during the entire model development,the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival.Consistent insigni-ficance and low coefficient values suggest that donor age does not impact patient survival in our dataset.Notably,there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption.When comparing donor age groups,transplantation using elderly grafts showed similar early graft function,similar graft(P=0.92),and patient survival rates(P=0.86),and no significant difference in the incidence of postoperative complications.CONCLUSION Our center's experience indicates that donor age does not play a significant role in patient survival,with elderly livers performing comparably to younger grafts when accounting for other risk factors.

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.

Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey

BACKGROUND Hepatitis B immunoglobulin(HBIG)in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus(HBV)reinfection after liver transplantation for HBV-associated disease.AIM To evaluate patients’satisfaction,preferences,and requirements for subcutaneous(SC),intramuscular(IM),and intravenous(IV)HBIG treatments.METHODS A self-completion,cross-sectional,online,22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France,Italy,and Turkey.Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint(trade-off)exercise.RESULTS Ninety patients were enrolled;32%,17%,and 51%were SC,IM,and IV HBIG users,respectively.Mean duration of treatment was 36.2 months.SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient,easiest to administer,least painful,and had the highest self-rating of treatment compliance.More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive(67%,28%,and 28%,respectively).In the target product profile assessment,76%of patients were likely to use hypothetical SC HBIG.In the conjoint exercise,administration route,frequency,and duration were key drivers of treatment preferences.CONCLUSION Ease,frequency,duration,and side effects of HBIG treatment administration were key drivers of treatment preferences,and SC HBIG appeared advantageous over IM and IV HBIG for administration ease,convenience,and pain.A hypothetical SC HBIG product elicited a favorable response.Patient demographics,personal preferences,and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Clinical application of COVID-19 vaccine in liver transplant recipients

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Use of machine learning models for the prognostication of liver transplantation: A systematic review

BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.

Comparison of different preoperative objective nutritional indices for evaluating 30-d mortality and complications after liver transplantation

BACKGROUND The nutritional status is closely related to the prognosis of liver transplant re-cipients,but few studies have reported the role of preoperative objective nutri-tional indices in predicting liver transplant outcomes.AIM To compare the predictive value of various preoperative objective nutritional indicators for determining 30-d mortality and complications following liver transplantation(LT).METHODS A retrospective analysis was conducted on 162 recipients who underwent LT at our institution from December 2019 to June 2022.RESULTS This study identified several independent risk factors associated with 30-d mor-tality,including blood loss,the prognostic nutritional index(PNI),the nutritional risk index(NRI),and the control nutritional status.The 30-d mortality rate was 8.6%.Blood loss,the NRI,and the PNI were found to be independent risk factors for the occurrence of severe postoperative complications.The NRI achieved the highest prediction values for 30-d mortality[area under the curve(AUC)=0.861,P<0.001]and severe complications(AUC=0.643,P=0.011).Compared to those in the high NRI group,the low patients in the NRI group had lower preoperative body mass index and prealbumin and albumin levels,as well as higher alanine aminotransferase and total bilirubin levels,Model for End-stage Liver Disease scores and prothrombin time(P<0.05).Furthermore,the group with a low NRI exhibited significantly greater incidences of intraabdominal bleeding,primary graft nonfunction,and mortality.CONCLUSION The NRI has good predictive value for 30-d mortality and severe complications following LT.The NRI could be an effective tool for transplant surgeons to evaluate perioperative nutritional risk and develop relevant nutritional therapy.

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.