Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma

With the increasing prevalence of living-donor liver transplantation(LDLT) for patients with hepatocellular carcinoma(HCC),some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation(DDLT) recipients.The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome,especially the recurrence of HCC,between LDLT and DDLT.While some studies report impaired recurrence- free survival and increased recurrence rates among LDLT recipients,others,including large database studies,report comparable recurrence- free survival and recurrence rates between LDLT and DDLT.Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression,but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases.In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients,there is no evidence to support the higher HCC recurrence after LDLT than DDLT,and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.

Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain

Background: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation(LDLT) is presented. Methods: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29(45.3%) females and 35(54.7%) males was 50.2 years(interquartile range, IQR 32.9–57.5). Twenty-two(34.4%) recipients had no portal hypertension. Three(4.7%) patients had a benign and 33(51.6%) a malignant tumor [19(29.7%) hepatocellular cancer, 11(17.2%) secondary cancer and one(1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months(IQR 41–159) and 39 months(22–91), respectively. Results: Right and left hemi-livers were implanted in 39(60.9%) and 25(39.1%) cases, respectively. Median weights of right-and left-liver were 810 g(IQR 730–940) and 454 g(IQR 394–534), respectively. Graft-to-recipient weight ratios(GRWRs) were 1.17%(right, IQR 0.98%-1.4%) and 0.77%(left, 0.59%-0.95%). One-and five-year patient survivals were 85% and 71%(right) vs. 84% and 58%(left), respectively. Oneand five-year graft survivals were 74% and 61%(right) vs. 76% and 53%(left), respectively. The patient and graft survival of right and left grafts and of very small( < 0.6%), small(0.6%–0.79%) and large( ≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3-and 12-month. No donor died while five(7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three(4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. Conclusions: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely with low morbidity. The recipient operation carries a major morbidity indicating an important learning curve. Shifting the risk from the donor to the recipient, by moving from the larger right-liver to the smaller left-liver grafts, should be further explored as this policy makes donor hepatectomy safer and may stimulate the development of transplant oncology.

Secondary non-resectable liver tumors:A single-center living-donor and deceased-donor liver transplantation case series

Background: During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT. Methods: Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine ( n = 18, 82%) and colorectal metastases ( n = 4, 18%);50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used;the median graft-to-recipient-weight ratios (GRWR) were 1.03%(IQR 0.86%- 1.30%) and 0.59%(IQR 0.51%- 0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17–107) in the DDLT group and 40 months (IQR 35–116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence. Results: The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively ( P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT ( P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2–2.2) vs. 3.3 (IQR 2.3–5.2) mg/dL;P = 0.02]. Conclusions: The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.

Salvage living-donor liver transplantation to previously hepatectomized hepatocellular carcinoma patients:is it a reasonable strategy?

Salvage liver transplantation (LT) has been performed for recurred hepatocellular carcinoma(HCC) or for deterioration of liver function after resection of HCC. Controversies arise, howeverover the technical feasibility of salvage LT in patientswho underwent liver surgery,

Helicobacter cinaedi bacteremia with cellulitis after ABO-incompatible living-donor liver transplantation: Case report

Helicobacter cinaedi(H. cinaedi), a Gram-negative spiral-shaped bacterium, is an enterohepatic nonHelicobacter pylori Helicobacter species. We report the first case of H. cinaedi bacteremia with cellulitis after liver transplantation. A 48-year-old male, who had been a dog breeder for 15 years, underwent ABO-incompatible living-donor liver transplantation for hepatitis C virus-induced decompensated cirrhosis using an anti-hepatitis B core antibody-positive graft. The patient was preoperatively administered rituximab and underwent plasma exchange twice to overcome blood type incompatibility. After discharge, he had been doing well with immunosuppression therapy comprising cyclosporine, mycophenolate mofetil, and steroid according to the ABO-incompatible protocol of our institution. However, 7 mo after transplantation, he was admitted to our hospital with a diagnosis of recurrent cellulitis on the left lower extremity, and H. cinaedi was detected by both blood culture and polymerase chain reaction analysis. Antibiotics improved his symptoms, and he was discharged at day 30 after admission. Clinicians should be more aware of H. cinaedi in immunocompromised patients, such as ABO-incompatible transplant recipients.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A singlecenter study

AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

Hepatofugal Portal Flow Associated with Acute Rejection in Living-donor Auxiliary Partial Orthotopic Liver Transplantation:A Report of One Case and Literature Review

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein.Based on histological findings,acute rejection was the suspected cause.The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies.The patient was discharged on the 30th postoperative day.It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection,and can be successfully treated by anti-rejection therapy.

Usefulness of Monitoring Stroke Volume Variations for Fluid Management During Pediatric Living-Donor Liver Transplantation

Purpose: Central venous pressure (CVP) is considered to be unsuitable as preload parameter. Stroke volume variation (SVV) has recently been reported to be effective as a preload and fluid responsiveness parameter, and its usefulness for fluid management during living-donor liver transplantation (LDLT). However, use of SVV has not been reported in children. Our aim is to evaluate the use of SVV as a target parameter of circulating blood volume during pediatric LDLT. Methods: This retrospective study was conducted in 40 consecutive patients aged between 5 and 109 months who underwent elective LDLT. Twenty patients underwent LDLT without FloTrac? (C group) and the rest patients underwent LDLT with the FloTrac? monitoring (F group). As a fluid management target, CVP was maintained at 10 mmHg in the C group and SVV at 10% in the F group. We compared MAP and CVP at the times of the greatest decrease within 5 minutes after reperfusion. Results: MAP after reperfusion was significantly decreased in both groups (P < 0.01), with the magnitude of decrease significantly greater in the C group compared with the F group (P = 0.02). MAP before and after reperfusion did not significantly differ between the groups. After reperfusion, CVP was nearly the same in both groups, with that in the C group slightly decreased and nearly no change in the F group. SVV after reperfusion was significantly increased (P < 0.001). Conclusion: When used as a target parameter for fluid management during pediatric LDLT, hemodynamic changes was less when SVV was used as the parameter of circulating blood volume.

Association of different central venous pressure levels with outcome of living-donor liver transplantation in children under 12 years

Background Pediatric liver transplantation is an important modality for treating biliary atresia.The overall survival(OS)rate of pediatric liver transplantation has significantly improved compared with that of 20 years ago,but it is still unsatisfactory.The anesthesia strategy of maintaining low central venous pressure(CVP)has shown a positive effect on prognosis in adult liver transplantation.However,this relationship remains unclear in pediatric liver transplantation.Thus,this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients.Methods This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure:low CVP(LCVP)(≤10 cmH2O,n=470)and high CVP(HCVP)(>10 cmH2O,n=242).The primary outcome measured in the study was the overall survival rate.The secondary outcomes included the duration of mechanical ventilation in the intensive care unit(ICU),length of stay in the ICU,and postoperative stay in the hospital.Patient demographic and perioperative data were collected and compared between the two groups.Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate.Results In the study,712 patients,including 470 in the LCVP group and 242 in the HCVP group,were enrolled.After propensity score matching,212 pairs remained in the group.The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses(P=0.018),and the HCVP group had a hazard ratio of 2.445(95%confidence interval,1.163–5.140).Conclusion This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay.

First successful bilateral living-donor lobar lung transplantation in China

Lung transplantation has been performed internationally as an effective treatment for a variety of end-stage lung＇diseases. A great disparity between the supply of donor organs and the demand of potential recipients has resulted in longer waiting time and annual increases in deaths on the lung transplant waiting list. Living-donor lobar lung transplantation （LDLLT） has become an established strategy to deal with the shortage of cadaveric donors. Encouraged by Starnes et al and Date et al, we began to apply the operation to a critically ill patient with bronchopulmonary dysplasia （BPD） firstly at Shanghai Pulmonary Hospital in China.

Liver volumetric and anatomic assessment in living donor liver transplantation: The role of modern imaging and artificial intelligence

The shortage of deceased donor organs has prompted the development of alternative liver grafts for transplantation.Living-donor liver transplantation(LDLT)has emerged as a viable option,expanding the donor pool and enabling timely transplantation with favorable graft function and improved long-term outcomes.An accurate evaluation of the donor liver’s volumetry(LV)and anatomical study is crucial to ensure adequate future liver remnant,graft volume and precise liver resection.Thus,ensuring donor safety and an appropriate graftto-recipient weight ratio.Manual LV(MLV)using computed tomography has traditionally been considered the gold standard for assessing liver volume.However,the method has been limited by cost,subjectivity,and variability.Automated LV techniques employing advanced segmentation algorithms offer improved reproducibility,reduced variability,and enhanced efficiency compared to manual measurements.However,the accuracy of automated LV requires further investigation.The study provides a comprehensive review of traditional and emerging LV methods,including semi-automated image processing,automated LV techniques,and machine learning-based approaches.Additionally,the study discusses the respective strengths and weaknesses of each of the aforementioned techniques.The use of artificial intelligence(AI)technologies,including machine learning and deep learning,is expected to become a routine part of surgical planning in the near future.The implementation of AI is expected to enable faster and more accurate image study interpretations,improve workflow efficiency,and enhance the safety,speed,and cost-effectiveness of the procedures.Accurate preoperative assessment of the liver plays a crucial role in ensuring safe donor selection and improved outcomes in LDLT.MLV has inherent limitations that have led to the adoption of semi-automated and automated software solutions.Moreover,AI has tremendous potential for LV and segmentation;however,its widespread use is hindered by cost and availability.Therefore,the integration of multiple specialties is necessary to embrace technology and explore its possibilities,ranging from patient counseling to intraoperative decision-making through automation and AI.

Post-liver transplant biliary complications:Current knowledge and therapeutic advances

Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors.Despite the remarkable advances in the surgical techniques and immunosuppressive therapy,the postoperative morbidity and mortality still remain high and the leading causes are biliary complications,which affect up to one quarter of recipients.The most common biliary complications are anastomotic and non-anastomotic biliary strictures,leaks,bile duct stones,sludge and casts.Despite the absence of a recommended treatment algorithm many options are available,such as surgery,percutaneous techniques and interventional endoscopy.In the last few years,endoscopic techniques have widely replaced the more aggressive percutaneous and surgical approaches.Endoscopic retrograde cholangiography is the preferred technique when duct-to-duct anastomosis has been performed.Recently,new devices and techniques have been developed and this has led to a remarkable increase in the success rate of minimally invasive procedures.Understanding the mechanisms of biliary complications helps in their early recognition which is the prerequisite for successful treatment.Aggressive endoscopic therapy is essential for the reduction of morbidity and mortality in these cases.This article focuses on the common post-transplant biliary complications and the available interventional treatment modalities.

Current techniques for AB0-incompatible living donor liver transplantation

For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible(AB0i) grafts. Improvements in AB0 i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0 i living donor liver transplantation(LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0 i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0 i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0 i LDLT is a feasible option today and almost free of severe complications.

Pediatric liver transplantation outcomes from a single center in Thailand

BACKGROUND Liver transplantation(LT)has become an acceptable curative method for children with several liver diseases,especially irreversible acute liver failure and chronic liver diseases.King Chulalongkorn Memorial Hospital is one of Thailand’s largest liver transplant centers and is responsible for many pediatric cases.AIM To report the experience with pediatric LT and evaluate outcomes of livingrelated vs deceased-donor grafts.METHODS This evaluation included children who underwent LT between August 2004 and November 2019.Data were retrospectively reviewed,including demographics,diagnoses,laboratory values of donors and recipients,the pediatric end-stage liver disease(PELD)or model for end-stage liver disease(MELD)score,graft source,wait time,perioperative course,postoperative complications,and survival rates.Continuous data were reported using the median and interquartile range.The Mann–Whitney U-test was used to compare the wait time between the living-related and deceased-donor groups.The chi-square or Fisher's exact test were used to compare the frequencies of between-group complications.Survival rates were calculated using the Kaplan–Meier method.RESULTS Ninety-four operated pediatric liver transplant patients were identified(54%were females).The median age at transplantation was 1.2(0.8-3.8)years.The median PELD and MELD scores were 20(13-26.8)and 19.5(15.8-26.3),respectively.Most grafts(81.9%)were obtained from living-related donors.The median wait time for the living donors was significantly shorter compared with the deceased donors at 1.6(0.3-3.1)mo vs 11.2(2.1-33.3)mo(P=0.01).Most patients were diagnosed with biliary atresia(74.5%),and infection was the most common complication within 30 d posttransplantation(14.9%).Without a desensitization protocol,9%of transplants were ABOincompatible.Eight hepatitis B core antibodies(anti-HBc)-negative recipients received positive anti-HBc grafts without different observed complications.The overall survival rate was 93.6%and 90.3%at 1 and 5 years,respectively.No graft loss during follow-up was noted among survivors.CONCLUSION A significant number of pediatric LT cases were reported in Thailand.Based on relatively comparable outcomes,ABO-incompatible and HBc antibody-positive grafts may be considered in an organ shortage situation.

A Questionnaire Survey in Kidney Transplant Outpatients: Factors Associated with Good Self-Management

It is very important for outpatients who have had a kidney transplant to take care of themselves after discharge. However, outpatients have limited access to medical care by hospital staff after discharge;therefore, medical staff are unaware of the patient’s living conditions, and the uncertainties and problems that they encounter related to self-management. We conducted a questionnaire survey among 161 of 200 outpatients who received kidney transplants to investigate their recognition and actual practice of daily self-management. To determine the characteristics of adherent outpatients, we divided patients into two groups (the adherent and non-adherent group) and compared them. The Chi-squared test was conducted to test the equality of proportions among the groups, and then multiple logistic regression analysis was used to explore the factors significantly associated with regularly taking medicine or failing to take medicine. As a result of the logistic regression model using demographic factors as independent factors, the periods after transplantation (2 - 5 and 5 - 10 years) and living-donor kidney transplantation or cadaveric kidney transplantation were selected as significant factors associated with good self-management. As a whole, 68.3% of the 145 patients were correctly predicted using the model. The results of this study suggest that in the short period after transplantation (2 - 5 years), cadaveric kidney transplantation and that the patient has a job are significant factors associated with good self-management. Behind these results, a unique Japanese concept, “amae”, could be found. Therefore, medical knowledge and techniques as well as cultural background should be studied.

Is there any correlation between Iiver graft regeneration and recipient's pretransplant skeletal muscle mass?-a study in extended Ieft Iobe graft Iiving-donor Iiver transplantation

Background:The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass(SMM).In living-donor liver transplantation(LDLT),liver graft regeneration(GR)represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient.Limited data are available on the correlation between pre-LDLT low SMM and GR.Methods:Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft.The skeletal muscle index(SMI)at L3 level was used for muscle mass measurement,and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity.GR was evaluated as rate of volume increase at 1 month post-LT[graft regeneration rate(GRR)].Results:The median GRR at 1 month post-LT was 91%(IQR,65-128%)and a significant correlation with graft volume-to-recipient standard liver volume ratio(GV/SLV)(rho-0.467,P<0.001),graft-to-recipient weight ratio(GRWR)(rho-0.414,P<0.001),donor age(rho-0.306,P=0.001),1 month post-LT cholinesterase serum levels(rho 0.397,P=0.002)and pre-LT low muscularity[absent vs.present GRR 97.5%(73.1-130%)vs.83.5%(45.2-110.9%),P=0.041]was noted.Moreover in male recipients,but not in women,it was shown a direct correlation with pre-LT SMI(rho 0.352,P=0.020)and inverse correlation with 1 month post-LT SMI variation(rho-0.301,P=0.049).A low GRR was identified as an independent prognostic factor for recipient overall survival(HR 6.045,P<0.001).Conclusions:Additionally to the hemodynamic factors of portal circulation and the quality of the graft,the metabolic status of the recipients has a significant role in the GR process.A pre-LT low SMM is associated with impaired GRR and this negative impact is more evident in male recipients.

Health-related quality of life of living liver donors 1 year after donation

Background:Improving the health-related quality of life(HRQOL)of living liver donors post-donation is an important aspect of care quality.Analyzing the HRQOL of living liver donors prospectively could help improve our understanding of the recovery of HRQOL and help improve the quality of donor care.In this study,we examined the HRQOL of living liver donors at pre-donation and at 1-year post-donation and analyzed the effect of pre-and post-donation factors on the donors'physical and mental HRQOL.Methods:This was a prospective study.During the enrollment period(August 2013 to December 2015),68 living liver donors completed the study questionnaires 5 times:at pre-donation and at 1,3,6,and 12 months post-donation.The Medical Outcomes Study Questionnaire Short Form-36,which yields both physical(PCS)and mental(MCS)component summary scores,was used to measure the HRQOL.The pre-and post-donation factors included donation ambivalence,recipients'physical condition,post-donation complications,and recipients'survival status.Results:Participants'mean PCS scores were 43.59 and 56.50 at 1 and 12 months after donation,respectively,whereas their mean MCS scores were 46.89 and 46.28,respectively.The mean PCS score was worse at 1 month after donation but improved significantly over time(P<0.05);conversely,the MCS was quite stable over time(P>0.05).A good PCS score was associated with no surgical complications of donation(coefficient=2.87,P=0.02),whereas a poor MCS score was associated with an education of less than a bachelor's degree(coefficient=?3.60,P=0.004),a higher Model for End-Stage Liver Disease(MELD)score in the recipient(coefficient=?0.13,P=0.03),and recipient death(coefficient=?3.48,P=0.03).Pre-donation ambivalence and sense of coherence were not significant predictors of the PCS or MCS scores.Conclusions:The impact of living liver donation on HRQOL was strongest in the early stages of the post-surgery period for the physical domain.Health-care professionals should carefully manage and monitor the progress of surgical outcomes,particularly in high-risk groups such as donors with a low education level or donors whose recipients have severe illness or end up dying after the surgery.Doing so may allow for suitable intervention opportunities to improve the HRQOL of living liver donors.