Combined liver and kidney transplantation in Guangzhou,China

BACKGROUND: When liver or kidney transplant can respectively cure end-stage liver or kidney disease, neither hepatic graft nor renal transplant alone can be used as a radical therapy for diseases which involve both liver and kidney. Combined liver and kidney transplantation commenced late in China, and the number of transplants has been limited. This study was designed to assess the effects of simultaneous combined liver and kidney transplantation (SLKT) on end-stage liver and kidney diseases. METHODS: Fifteen patients who had received SLKT from 1996 to 2006 in the First Affiliated Hospital of Sun Yat-Sen University were reviewed. They included 5 patients with polycystic liver and kidney, 5 patients with hepatic cirrhosis and renal failure, and 5 patients with fulminant hepatic failure and hepatorenal syndrome (11 men and 4 women; average age 43.5 years). All patients had combined liver and kidney transplantation. RESULTS: The 5 patients with polycystic liver and kidney have survived for more than one year after SLKT, and the longest survival has been 5 years. Three of the 5 patients with hepatic cirrhosis and renal failure have survived more than two years; one died perioperatively and the other died from recurrence of hepatitis B 18 months after the operation. Three of the 5 patients with fulminant hepatic failure and hepatorenal syndrome have survived for two years, and 2 died of multiple organ failure during the operation. CONCLUSIONS: SLKT is an effective therapy for end-stage liver and kidney disease but the indications of SLKT for hepatorenal syndrome should be strict. SLKT may immunologically protect the renal graft.

Shifting perspectives in liver diseases after kidney transplantation

Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic disorders.Over the past decade,the aetiology of liver disease in kidney recipients has changed significantly.These relates to the use of direct-acting antiviral agents against hepatitis C virus,the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity.In addition,the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients.This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.

Small bowel obstruction caused by a bezoar following an adult simultaneous liver-kidney transplantation:A case report

BACKGROUND Small bowel obstructions(SBOs)are common following a large intra-abdominal operation;however,SBOs caused by bezoars are unreported in patients following liver-kidney transplantation procedures,particularly in adults.CASE SUMMARY A 65-year-old Caucasian female presented with nausea and nonbilious emesis during her postoperative course following a simultaneous liver-kidney transplantation.She developed worsening nausea and vomiting with significant abdominal distension and obstipation.Computed tomography imaging showed a marked abnormal dilation of multiple small bowel loops with a distinct transition point that was suggestive of a small bowel obstruction.An exploratory laparotomy revealed a foreign body in the intestinal track approximately 30 cm from the ileocecal valve.The foreign body was extracted and identified as a bezoar with hair follicles and old digestive contents.Following the operation,the patient demonstrated rapid clinical improvement with resolution of nausea,emesis,and progress in bowel motility.CONCLUSION SBOs caused by bezoars can occur immediately following a liver-kidney transplantation and should not be discounted as a diagnosis.

Lesson learnt from 60 years of liver transplantation:Advancements,challenges,and future directions

Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.

Combined liver and kidney transplantation in children and long-term outcome

Combined liver-kidney transplantation(CLKT)is a rarely performed complex surgical procedure in children and involves transplantation of kidney and either whole or part of liver donated by the same individual(usually a cadaver)to the same recipient during a single surgical procedure.Most common indications for CLKT in children are autosomal recessive polycystic kidney disease and primary hyperoxaluria type 1.Atypical haemolytic uremic syndrome,methylmalonic academia,and conditions where liver and renal failure co-exists may be indications for CLKT.CLKT is often preferred over sequential liver-kidney transplantation due to immunoprotective effects of transplanted liver on renal allograft;however,liver survival has no significant impact.Since CLKT is a major surgical procedure which involves multiple and complex anastomosis surgeries,acute complications are not uncommon.Bleeding,thrombosis,haemodynamic instability,infections,acute cellular rejections,renal and liver dysfunction are acute complications.The long-term outlook is promising with over 80%5-year survival rates among those children who survive the initial six-month postoperative period.

Kidney transplantation after liver transplantation

Kidney transplantation after liver transplanta tion（KALT） offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efficacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta tion because of calcineurin inhibitor（CNI）-induced neph rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.

Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation

New nucleos(t)ide analogues(NAs) with high genetic barrier to hepatitis B virus(HBV) resistance(such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation(LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physi-cians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decom-pensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus(HCV) recurrence after LT, which is the combination of sub-cutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infec-tion has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.

A single center experience of combined liver and kidney transplantation

Objective To summarize the experience of treating the end stage of liver disease complicated with renal failure using combined liver - kidney transplantation. Methods The clinical data of 28 cases receiving combined liver - kidney transplantation were retrospectively ana-

Effect of transplant center volume on post-transplant survival in patients listed for simultaneous liver and kidney transplantation

AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.

Liver transplantation for liver failure in kidney transplantation recipients with hepatitis B virus infection

To the Editor:Worldwide,approximately 400 million patients have chronic hepatitis B virus(HBV)infection[1].Because of the high incidence of HBV in China,the incidence of HBV infection in uremia and kidney transplantation(KTx)patients is 2.5%and 2.7%,respectively[2].Since the first successful organ transplant conducted between twins in 1954,refined surgical techniques,improved immunosuppressive protocols,and improved perioperative management of transplant patients have resulted in improved patient and graft survivals following K Tx[3].However,the K Tx community is now challenged with liver failure due to the increased risk of HBV viral activation and replication induced by immunosuppressive therapy.Harnett et al.[4]highlighted that KTx recipients with HBV infection had lower 5-year survival(61%)than patients on dialysis(85%).Although these KTx recipients were treated with regular anti-HBV therapy,the incidence of liver failure was increased in KTx patients with HBV infection.Currently,isolated liver transplantation(LTx),sequential liver and kidney transplantation(SLKT),and combined liver and kidney transplantation(CLKT)are the optimal treatments for patients with liver failure and hepatorenal syndrome[5].However,the outcomes of KTx recipients following isolated LTx,SLKT or CLKT for HBV-associated liver failure remain to be studied.Herein,we report our experience in ten HBV-positive KTx recipients with liver failure undergoing LTx.

Physiology and health assessment,risk balance,and model for endstage liver disease scores:Postoperative outcome of liver transplantation

BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.

Large-for-size syndrome prophylaxis in infant liver recipients with low body mass

Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.

Human leukocyte antigen and donor-specific antibodies in liver transplantation

In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.

Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

Expanding role of antibodies in kidney transplantation

The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.

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.

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.

Evolution of liver transplantation in the metabolic dysfunctionassociated steatotic liver disease era: Tracking impact through time

Liver transplantation(LT)for metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing globally due to rising rates of obesity and metabolic syndrome,posing significant challenges.MASLD patients typically present with advanced age,higher body mass index(BMI),and metabolic com-orbidities such as diabetes,hypertension,and dyslipidemia.Comprehensive pre-transplant evaluations are crucial for assessing surgical risks and preparing patients for transplantation.MASLD patients with higher BMI may experience longer operative times,potentially affecting intraoperative outcomes.In the months following LT,MASLD recipients face persistent challenges,including a higher incidence of metabolic syndrome and cardiovascular events compared to non-MASLD recipients.However,survival rates at 1-,3-,and 5-years post-LT do not markedly differ from other etiologies,indicating comparable surgical outcomes.Optimizing outcomes in MASLD patients undergoing LT demands a multidisciplinary approach from pre-transplant assessment to post-transplant care.Strategies must address metabolic comorbidities,manage cardiovascular health,and monitor steatosis recurrence,which can be exacerbated by obesity and diabetes.This approach aims to mitigate long-term graft complications and mortality risks,ultimately enhancing transplant success and patient well-being.Continued research is essential to refine these approaches and meet the evolving challenges posed by MASLD as a leading indication for LT worldwide.