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Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation
Abstract
Live donor liver transplantation (LDLT) has become increasingly common in the United States and around the world. In this study, we compared the outcome of 764 patients who received LDLT in the United States and compared the results with a matched population that received deceased donor transplantation (DDLT) using the United Network for Organ Sharing (UNOS) database. For each LDLT recipient (n = 764), two DDLT recipients (n = 1,470), matched for age, gender, race, diagnosis, and year of transplantation, were selected from the UNOS data after excluding multiple organ transplantation or retransplantation, children, and those with incomplete data. Despite our matching, recipients of LDLT had more stable liver disease, as shown by fewer patients with UNOS status 1 or 2A, in an intensive care unit, or on life support. Creatinine and cold ischemia time were also lower in the LDLT group. Primary graft nonfunction, hyperacute rejection rates, and patient survival by Kaplan-Meier analysis were similar in both groups (2-year survival was 79.0% in LDLT vs. 80.7% in case-controls; P = .5), but graft survival was significantly lower in LDLT (2-year graft survival was 64.4% vs. 73.3%; P < .001). Cox regression (after adjusting for confounding variables) analysis showed that LDLT recipients were 60% more likely to lose their graft compared to DDLT recipients (hazard ratio [HR] 1.6; confidence interval 1.1-2.5). Among hepatitis C virus (HCV) patients, LDLT recipients showed lower graft survival when compared to those who received DDLT. In conclusion, short-term patient survival in LDLT is similar to that in the DDLT group, but graft survival is significantly lower in LDLT recipients. LDLT is a reasonable option for patients who are unlikely to receive DDLT in a timely fashion.
... In 2002, the New York State Committee on Quality Improvement in Living Liver Donation recommended prohibiting LDLT in patients with a MELD score greater than 25 because of the possibility of a futile transplantation [11] . There is also controversy regarding the safety of partial grafts in patients with a high MELD score [12,13] . ...
... The median length of hospital stay for living donors was 12 days (IQR, [10][11][12][13][14]. The readmission rate within 6 months was 3.33%. ...
... From a living-donor perspective, there was no mortality, and only 4.17% of patients experienced major complications (Clavien-Dindo grade ≥ 3). Other authors have recommended against proceeding with LDLT in patients with a high MELD score [11][12][13] , but our results demonstrated that even patients with a MELD score greater than or equal to 30 had generally similar outcomes after LDLT, compared to DDLT. Thus, if an eligible living-donor is available, LDLT can improve patient survival in patients with a MELD score greater than or equal to 30. ...
Background:
The benefits of living-donor liver transplantation (LDLT) in patients with a high Model for End-stage Liver Disease (MELD) score (who have high waitlist mortality) are unclear. Regional availability of deceased-donor organs must be considered when evaluating LDLT benefits. We aimed to compare the survival benefit of intended-LDLT to awaiting deceased-donor liver transplantation (DDLT) in patients with a MELD score ≥30 in a region with severe organ shortage.
Materials and methods:
This retrospective review included 649 patients with a MELD score ≥30 placed on the liver transplantation waitlist. They were divided into Intended-LDLT (n=205) or Waiting-DDLT (n=444) groups based on living-donor eligibility and compared for patient survival from time of waitlisting. Post-transplantation outcomes of transplant recipients and living donors were analyzed.
Results:
Intended-LDLT patients had higher 1-year survival than Waiting-DDLT patients (53.7% vs. 28.8%, P<0.001). LDLT was independently associated with lower mortality (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.48-0.79; P<0.001). During follow-up, 25 patients were de-listed, 120 underwent LDLT, 170 underwent DDLT, and 334 remained on the waitlist. Among patients undergoing transplantation, the risk of post-transplantation mortality was similar for LDLT and DDLT after adjusting for pre-transplantation MELD score (HR, 1.86; 95% CI, 0.73-4.75; P=0.193), despite increased surgical complications after LDLT (33.1% vs. 19.4%, P=0.013). There was no mortality among living-donors, but 4.2% experienced complications of grade 3 or higher.
Conclusions:
Compared to awaiting DDLT, LDLT offers survival benefits for patients with a MELD score ≥30, while maintaining acceptable donor outcomes. LDLT is a feasible treatment for patients with a MELD score ≥30 in regions with severe organ shortage.
... Fifteen studies investigated patients with various liver diseases, 10 studies were about hepatitis B/C virus-related diseases, and 14 studies focused on HCC. Three studies [21,37,40] were derived from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, 3 studies [20,39,46] were based on the United Network for Organ Sharing, 1 study [18] was derived from the University Health System Consortium and Scientific Registry of Transplant Recipients, 1 study [14] was based on the China Liver Transplant Registry, and the rest of the studies were derived from a single center or from multiple institutions. These studies were conducted in the east (n = 14) and in the west (n = 25). ...
... Six studies [11,16,20,31,32,40] reported CIT, and all six of them suggested it was shorter in LDLT. There was significant heterogeneity (P < 0:00001, I 2 = 96%). ...
Background:
Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial.
Method:
A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed.
Results:
Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself.
Conclusions:
LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.
... LD grafts are not subjected to major cold ischemia, and the role of steatosis to the poor performance of the graft should therefore be minimum 20 . Short waiting time, the capacity to adjust the cold ischemic time and an increase in the organ storage are the major merits of LDLT 21 . Morbidity and mortality of the donor are the demerits of LDLT 21 . ...
... Short waiting time, the capacity to adjust the cold ischemic time and an increase in the organ storage are the major merits of LDLT 21 . Morbidity and mortality of the donor are the demerits of LDLT 21 . The most important difficulty in post-transplant morbidity in the recipients of LDLT is seen in surgical complications 22 . ...
Objective: Prognosis models play a significant role in forecasting the patient's survival in Organ transplantation. To review the impact of machine learning methods in predicting the of survival of patients who undergoes Liver Transplantation using a Multilayer Perceptron Artificial Neural Network model with an extensive discussion of all the medical aspects is the key objective of this paper. Methods/Analysis: Medical practitioners studied various parameters during pretransplantation for predicting the survival of a patient. This study considered those parameters and reviewed whether these parameters have any vital part in the survival rate of a patient after Liver Transplantation (LT). This study also compared various scores including Model for End Stage Liver Disease (MELD) score, Emory score and Child score that are used in survival prediction. Currently the medicinal specialists estimate the outcome of LT with MELD score. We employed a detailed learning about the health aspects of LT and various machine learning techniques used in this area. In order to perform the experimentation, the dataset was congregated from the United Network for Organ Sharing transplant database (n = 65534). With the three layer architecture, the model trains the attributes of donors, recipient and transplantation using back propagation algorithm. 10-fold cross validation was applied in each training and test set before training. During the training process, the appropriate donor-recipient pairs were found out and obtained the best liver patient survival in transplantation. Findings: We conducted a comprehensive study about LT for the liver patient survival prediction. We proposed a Multilayer Perceptron Artificial Neural Network model to predict the survival rate after LT with 99.74% accuracy using United Network Organ Sharing registry. We also compared the performance of proposed model with existing models and proved that proposed model produced more accuracy than other models. Novelty/Improvement: The multilayer perceptron model succeeded clinical scores in terms of high accuracy, sensitivity and specificity. Machine learning techniques show better performance than conservative numerical methods in donor, recipient and transplantation attributes which are used to predict the survival. Due to less expensive and producing reliable solutions with rich datasets, machine learning techniques have been succeeded the conventional statistical methods and medical scoring systems. The proposed model predicts a promising accuracy for the prediction of best survival rates after.
... In Asia, LDLT is mainly used because this procedure is more acceptable and accounts for 90% of liver transplants; however, in the West, DDLT is the mainstream and accounts for 95% of all liver transplants in the United States [1][2][3]. The one-year patient survival rates for adults and children after primary liver transplantation were 94% and 94.4%, respectively [6], and the short-term patient survival rates were not significantly different between patients treated with LDLT and DDLT [7]. The survival rate following transplantation has significantly improved due to advancements in surgery and the development of immunosuppressive agents [8][9][10]. ...
Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = −0.72 and −0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.
... 6 One of the advantages is shorter cold ischemia time (CIT). 7 This shorter CIT brings into question the use of preservation solutions in living donor grafts. Data on the use of preservatives in LDLT are limited‚ and one of the most extensive and recent studies from Mainland China compared the UW with HTK in a propensity-matched 106 pairs of patients. ...
Preservation solutions are required for organ viability in deceased donor liver transplantation (LT). However, their role in live donor LT (LDLT) has not been standardized.
Methods:
Eighty adult recipients who underwent right lobe LDLT at the Department of Liver Transplantation Surgery, Gambat, Pakistan, were studied. Based on shorter cold ischemia time and no back table reconstruction work, recipients were assigned to receive "no preservation solution" (cases/non-histidine-tryptophan-ketoglutarate group; n = 40) or "HTK group" (controls; n = 40). Early allograft dysfunction (bilirubin, transaminases, and international normalized ratio), postoperative complications (biliary and vascular), hospital stay, and 1-y survival were reported. The direct cost was also reported.
Results:
Demographics and clinical characteristics were comparable in the 2 groups. Comparing cases versus controls, mean bilirubin, alanine aminotransferase, aspartate aminotransferase, and international normalized ratio on postoperative day 7 were similar in the 2 groups. Five (12.5%) cases and 4 (10%) controls developed early allograft dysfunction (P = 0.72). Post-LT complications (biliary leak 2.5% in cases versus 0 in control), strictures (15% in cases versus 17.5% in controls), hepatic artery thrombosis (2.5% versus 00%)' and portal vein thrombosis (0 versus 2.5%) were comparable. Mean hospital stay (10.80 + 2.36 and 11.78 + 2.91 d) and 30 d mortality (2.5% versus 5%) were also comparable. Finally, 1-y survival based on Kaplan-Meier analysis was comparable in both groups (ie, 92.5%; non-HTK group versus 90%; HTK group) (P = 0.71). The direct cost of using a non-HTK-based approach was less than the HTK solution.
Conclusion:
In a selected cohort of right lobe LDLT recipients, preservation solutions can be avoided safely with comparable outcomes.
... In contrast to the advantage of receiving a kidney from a living donor relative to receiving one from a deceased donor [15], live liver transplants have no mortality advantage over cadaveric liver transplants [16]. Therefore, the incentive to become a living liver donor is not the same as the incentive to become a living kidney donor. ...
Previous research shows that countries with opt-out consent systems for organ donation conduct significantly more deceased-donor organ transplantations than those with opt-in systems. This paper investigates whether the higher transplantation rates in opt-out systems translate into equally lower death rates among organ patients registered on a waiting list (i.e., organ-patient mortality rates). We show that the difference between consent systems regarding kidney- and liver-patient mortality rates is significantly smaller than the difference in deceased-donor transplantation rates. This is likely due to different incentives between the consent systems. We find empirical evidence that opt-out systems reduce incentives for living donations, which explains our findings for kidneys. The results imply that focusing on deceased-donor transplantation rates alone paints an incomplete picture of opt-out systems’ benefits, and that there are important differences between organs in this respect.
... However, despite these promising results several studies have reported inconsistent graft survival rates between LDLT and standard cadaveric liver donations. Some analyses have demonstrated decreased graft survival rates in LDLT (56,57), while more recent studies appear to demonstrate similar long-term 10-year survival rates between patients receiving grafts from living donors and deceased donor grafts (55). For this reason, LDLT is reserved for high volume centres with specialist expertise due to the complexities of the procedure which requires a deep understanding of the physiological requirements of the graft to ensure sufficient hepatic regeneration and minimize donor risk. ...
Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality and dropout rates remain problematic and this concern has resulted in increased efforts to expand the donor pool to meet the unmet needs of the population. This is even more challenging when coupled with an ever-growing recipient pool, candidate waiting lists and an ageing population. Over the past two decades, there has been a considerable focus on extended criteria organs, donations after cardiac death and alternative avenues for marginal liver use. With careful donor selection and recipient matching, these livers may help bridge the gap between supply and demand and placate the ever-expanding recipient pool. Here, we present a summary of recent developments by the transplant community addressing the issues of a growing donor and recipient pool.
... The use of hemiliver grafts for high-MELD recipients is thus controversial [25], and there is also no universally accepted cut-off value for MELD in SLT/LDLT recipients. Early studies have reported the long-term outcomes of patients with high or very high MELD scores [10,[26][27][28][29], demonstrating that the survival rate of patients with an MELD score ≥ 36 was significantly reduced in AHLT. At present, it is generally considered safe to perform HLT in patients with MELD scores < 25; however, there is still considerable inconsistency regarding the outcomes of patients with MELD scores between 25 and 40 [30][31][32][33]. ...
Background
Adult hemiliver transplantation (AHLT) is an important approach given the current shortage of donor livers. However, the suitability of AHLT versus adult whole liver transplantation (AWLT) for recipients with high Model for End-Stage Liver Disease (MELD) scores remains controversial.
Methods
We divided patients undergoing AHLT and AWLT into subgroups according to their MELD scores (≥ 30: AHLT, n = 35; AWLT, n = 88; and < 30: AHLT, n = 323; AWLT, n = 323). Patients were matched by demographic data and perioperative conditions according to propensity scores. A cut-off value of 30 for MELD scores was determined by comparing the overall survival data of 735 cases of nontumor liver transplantation.
Results
Among patients with an MELD score ≥ 30 and < 30, AHLT was found to be associated with increased warm ischemia time, operative time, hospitalization time, and intraoperative blood loss compared with AWLT (P < 0.05). In the MELD ≥ 30 group, although the 5-year survival rate was significantly higher for AWLT than for AHLT (P = 0.037), there was no significant difference between AWLT and AHLT in the MELD < 30 group (P = 0.832); however, we did not observe a significant increase in specific complications following AHLT among patients with a high MELD score (≥ 30). Among these patients, the incidence of complications classified as Clavien-Dindo grade III or above was significantly higher in patients undergoing AHLT than in those undergoing AWLT (25.7% vs. 11.4%, P = 0.047). For the MELD < 30 group, there was no significant difference in the incidence of complications classified as Clavien-Dindo grade III or above for patients undergoing AHLT or AWLT.
Conclusion
In patients with an MELD score < 30, AHLT can achieve rates of mortality and overall survival comparable to AWLT. In those with an MELD score ≥ 30, the prognosis and incidence of complications classified as Clavien-Dindo III or above are significantly worse for AHLT than for AWLT; therefore, we may need to be more cautious regarding the conclusion that patients with a high MELD score can safely undergo AHLT.
... Furthermore, patients who require reoperation are more likely to develop additional complications and, in general, have increased morbidity and mortality [2,5,6]. Several recent studies have reported that reoperation rates are higher among LDLT patients than among deceased-donor liver transplantation (DDLT) cases [7][8][9]. Therefore, for complications requiring reoperation in LDLT patients, appropriate decision-making and treatment plans remain important and time-sensitive issues. In this study, we analyzed the causes, risk factors, and outcomes in patients requiring reoperation within 30 days of adult-toadult LDLT. ...
Background:
Patients who undergo reoperation after living-donor liver transplantation (LDLT) have poor outcomes. However, the specific outcomes of patients undergoing reoperation due to gastrointestinal (GI) tract-related complications following adult LDLT are relatively unknown. In the present study, we investigated the relationship between the causes and outcomes of reoperation after LDLT and classified the risk groups.
Methods:
We performed a retrospective analysis of 506 patients who underwent LDLT at Samsung Medical Center in Seoul between 2010 and 2016.
Results:
Among 506 adult LDLT recipients, 98 (19.4%) underwent reoperation. The causes for reoperation included bleeding (n=39, 39.8%), vascular complications (n=26, 26.5%), wound complications (n=12, 12.2%), bile leakage (n=7, 7.1%), GI tract complications (n=6, 6.1%), and others (n=8, 8.1%). Based on a multivariate analysis, we identified prolonged operation time, hospitalization days, and a history of previous hepatocellular carcinoma-related operation as independent risk factors for reoperation. Patient survival after 3 months, 1 year, 3 years, and 5 years was 96.3%, 90.6%, 82.5%, and 79.4% in the non-reoperation group and 95.9%, 82.7%, 72.8% and 69.3% in the reoperation group, respectively. Patient survival in the reoperation group was significantly lower than that in the non-reoperation group (P=0.018). In the reoperation group, the survival rates of patients with GI tract-related complications-including bile leakage and GI tract complications-were significantly worse than those of patients with non-GI tract-related complications such as bleeding, vascular complications, and wound complications (P<0.001).
Conclusions:
Our results showed that patient outcomes are poor after early reoperation after LDLT and that patients with GI tract-related complications have a higher risk of mortality.
... In Western countries, the majority of liver transplantation is deceased donor liver transplantation. Therefore, living donor liver transplantation (LDLT) is recognized as an alternative to increase the donor pool and reduce the waiting list mortality of patients [1,2]. In many Asian countries, LDLT accounts for the majority of liver transplant procedures because of the severe deceased organ shortage, which has led to the development of unique technical and logistical innovations in LDLT [3]. ...
The clinical significance of the right posterior segment (RPS) graft in living donor liver transplantation (LDLT) is unknown because of its limited use and technical concerns. This study aimed to review published studies investigating outcomes of RPS grafts. The systematic literature search was conducted to retrieve data from Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. Among the 388 articles, six retrospective studies from Asian countries were included. The overall incidences of major and minor complications after RPS graft procurement were 5.6% and 34.6%, respectively and no donor deaths were reported. RPS graft recipients had the following postoperative complications: overall mortality rate, 14.5%; bile leakage, 8.7%, biliary stenosis, 18.8%, hepatic artery thrombosis, 8.7%, and liver re-transplantation, 2.9%. The RPS graft can be considered as an option for a living liver graft respecting donor safety under strict selection criteria and surgical strategy. The precise evaluation and understanding of anatomical variations and volumetric analyses is critical for selecting donors and planning the surgical strategy in the RPS grafts procurement. The RPS grafts procurement requires carefully dissection of the hepatic artery and portal vein, safely confirmation of the bile duct, and precisely parenchymal transection. However, further experience is needed to clarify the significance of the RPS graft in LDLT. The special technical requirements should limit this donor procedure to centers with a high level of experience in LDLT.
... Therefore, the use of a living donor is an alternative to expand the organ pool (2). There are some studies suggesting that living donor liver transplantation (LDLT) should be the preferred method for patients with HCC because of a shorter waiting time for the liver, shorter cold ischemia time, and virtually no warm ischemia damage (3,4). However, some of the researchers suggest that the results of deceased donor liver transplantation (DDLT) are better (5,6). ...
Background/Aims: The aim of this study was to evaluate the effect of the Milan criteria on the hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrence in patients who underwent living donor liver transplantation due to HBV-induced cirrhosis and HCC. Materials and Methods: We evaluated a total of 142 patients, 88 who underwent transplantation due to HBV-induced cirrhosis and 54 due to HCC, between 2009 and 2014. In the posttranplant period, after the HBsAg seroconversion, 400 IU of hepatitis B immunoglobulin were applied intramuscularly every 2 weeks, and daily nucleos(t)ide analogs were continued as prophylaxis. The HBV recurrence was defined as the presence of HBsAg in serum. Patients were screened for alpha-fetoprotein levels and imaging for evaluation of HCC recurrence. Results: The average follow-up period was 26 (2-65) months. Fifty-four patients had HCC. The HCC recurrence was observed in 12 patients during the follow-up period. The HBV recurrence was observed in four patients. Three of the patients who developed HBV recurrence had liver transplantation due to HCC. Tumor recurrence was observed 1.4-12 months following the HBV recurrence. The HCC recurrence within the Milan criteria and beyond the Milan criteria was 0% vs. 28.4 % in the first year and 3.4% vs. 47.5% in the third year. The cumulative incidence of the HBV recurrence was 2.8% and 3.7% for the first year and 3.7% for the third year. The HBV recurrence was more frequently detected in patients with HCC (p=0.048), especially with HCC beyond the Milan criteria (p=0.044). Conclusion: The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who underwent liver transplantation due to HCC with exceeding Milan criteria.
... However, there was no difference in the 2 donor types for biliary complications and rejection (Table 3). Contrary to this study, many other western studies showed higher complication and readmissions in LDLT recipients (6,7,14). Samstein et al. (13) also reported LDLT recipients had a significantly higher probability of technical complications, including bile leaks, biliary strictures and biliary tree infections, but they found a decreasing trend in the probability of biliary stricture in centers performing the highest number of LDLTs per year. ...
Transplantation studies about the clinical differences according to the type of donors are mostly conducted in western countries with rare reports from Asians. The aims of this study were to evaluate the clinical impacts of the type of donor, and the predictors of 1-year mortality in patients who underwent liver transplantation (LT). This study was performed for liver transplant recipients between May 2010 and December 2014 at the Pusan National University Yangsan Hospital. A total of 185 recipients who underwent LT were analyzed. Of the 185 recipients, 109 (58.9%) belonged to the living donor liver transplantation (LDLT) group. The median age was 52.4 years. LDLT recipients had lower model for end-stage liver disease (MELD) score compared with better liver function than deceased donor liver transplantation (DDLT) recipients (mean ± standard deviation [SD], 12.5 ± 8.3 vs. 24.9 ± 11.7, respectively; P < 0.001), and had more advanced hepatocellular carcinoma (HCC) (62.4% vs. 21.1%, respectively; P = 0.001). In complications and clinical outcomes, LDLT recipients showed shorter stay in intensive care unit (ICU) (mean ± SD, 10.8 ± 8.8 vs. 23.0 ± 13.8 days, respectively, P < 0.001), ventilator care days, and post-operative admission days, and lower 1-year mortality (11% vs. 27.6%, respectively, P = 0.004). Bleeding and infectious complications were less in LDLT recipients. Recipients with DDLT (P = 0.004) showed higher mortality in univariate analysis, and multi-logistic regression analysis found higher MELD score and higher preoperative serum brain natriuretic peptide (BNP) were associated with 1-year mortality. This study may guide improved management before and after LT from donor selection to postoperation follow up.
... No significant difference in outcome could be identified between both types of grafts. The results from LDLT appear to show good long term survival rates with retrospective studies showing comparable rates to OLT [82,86,87] . Some other retrospective studies showed a higher rate of tumor recurrence with LDLT than with conventional OLT [81,83,84] . ...
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a poor prognosis if untreated. It is ranked the third among the causes of cancer-related death. There are multiple etiologic factors that can lead to HCC. Screening for early HCC is challenging due to the lack of well specific biomarkers. However, early diagnosis through successful screening is very important to provide cure rate. Liver transplantation (LT) did not gain wide acceptance until the mid-1980s, after the effective immunosuppression with cyclosporine became available. Orthotopic LT is the best therapeutic option for early, unresectable HCC. It is limited by both, graft shortage and the need for appropriate patient selection. It provides both, the removal of tumor and the remaining cirrhotic liver. In Milan, a prospective cohort study defined restrictive selection criteria known as Milan criteria (MC) that led to superior survival for transplant patients in comparison with any other previous experience with transplantation or other options for HCC. When transplantation occurs within the established MC, the outcomes are similar to those for nonmalignant liver disease after transplantation. The shortage of organs from deceased donors has led to the problems of long waiting times and dropouts. This has led to the adoption of extended criteria by many centers. Several measures have been taken to solve these problems including prioritization of patients with HCC, use of pretransplant adjuvant treatment, and living donor LT.
... Partial hepatic allografts from live donors, compared with deceased donors, have been found to reduce the risk of the recipient dying on the waiting list. And the recipient survival is comparable to that in cadaveric liver transplantation [5][6][7][8][9]. ...
Objective
To document the safety and efficacy of laparoscopic living donor hepatectomy in comparison with open liver resection for living donor liver transplantation.
Methods
Medline database, EMASE and Cochrane library were searched for original studies comparing laparoscopic living donor hepatectomy (LLDH) and open living donor hepatectomy (OLDH) by January 2015. Meta-analysis was performed to evaluate donors’ perioperative outcomes.
Results
Nine studies met selection criteria, involving 1346 donors of whom 318 underwent LLDH and 1028 underwent OLDH. The Meta analysis demonstrated that LLDH group had less operative blood loss [patients 1346; WMD: -56.09 mL; 95%CI: -100.28-(-11.90) mL; P = 0.01], shorter hospital stay [patients 737; WMD: -1.75 d; 95%CI: -3.01-(-0.48) d; P = 0.007] but longer operative time (patients 1346; WMD: 41.05 min; 95%CI: 1.91–80.19 min; P = 0.04), compared with OLDH group. There were no significant difference in other outcomes between LLDH and OLDH groups, including overall complication, bile leakage, postoperative bleeding, pulmonary complication, wound complication, time to dietary intake and period of analgesic use.
Conclusions
LLDH appears to be a safe and effective option for LDLT. It improves donors’ perioperative outcomes as compared with OLDH.
... 50,51 The risk to the recipient must equal or exceed risk to the donor to justify a LDLT. 52 LDLT is possible because of segmental anatomy of the liver (Figure 3). Surgeons are able to create grafts of varying sizes depending on the recipients and donors requirement for liver mass. ...
The incidence of end stage liver disease and liver transplantation is on the rise in Kerala. All practicing doctors should have an insight into the indications, contraindications, évaluation leading to and complications following liver transplantation. Liver transplantation is now an accepted modality of treatment in end stage liver disease and hepatocellular carcinoma. With potent im-munosuppression and newer surgical techniques the 5 year survival rate following liver transplantation is above 75%. It is higher than that for surgeries for most gastro-intestinal cancers. The process to reach liver transplantation starts with early referral to the transplant centre, where extensive investigations performed. Once the patient is accepted into the waiting list, then prioritization for the transplant relies on the MELD score as well as matching the blood group and patient size. Immunosuppression after transplant requires a balance between prevention of graft rejection and minimization of the side effects of immunosuppressive drugs. Lifelong after-care is crucial for long-term graft and patient survival after liver transplantation.
... More recently, model for end-stage liver disease has been used as a predictor of death within 3 months due to chronic liver disease. Model for end-stage liver disease is calculated from serum creatinine, bilirubin, and international normalized ratio [11]. ...
... Risk factors for the development of CKD after LT include cyclosporine use, dose and levels (6)(7)(8), recipient age (1,2,9), number of years elapsed after LT(1), acute kidney injury (AKI) post-LT (2), hepatitis C infection (2,10,11), pre-or post-transplant diabetes mellitus (2,7,9,10), pre-or post-transplant hypertension (2,8,9,11) pre-transplant eGFR (2,3,6), and decline in eGFR within the first year post-LT (1,3,(6)(7)(8)10). Long term outcomes of living donor LT (LDLT) as compared to deceased donor LT (DDLT) have yielded mixed results, often favoring the latter (12)(13)(14)(15)(16)(17). However, increased center experience and improved surgical techniques are associated with improved LDLT outcomes (12,14,18). ...
Few studies have explored whether the type of LT, deceased donor LT (DDLT) or living donor LT (LDLT), impacts long term renal outcomes. We performed a retrospective analysis of 220 LT recipients at our institution to study their renal outcomes at 10 years. Exclusion criteria were, age≤18 years, graft survival ≤ 6 months and multiorgan transplants; 108 DDLTs and 62 LDLTs were eligible. At baseline, DDLTs had a lower eGFR than LDLTs and 10.2% of DDLTs were on dialysis as compared to 0% of LDLTs. At 10 years, 7 DDLT and 3 LDLT recipients required dialysis or renal transplant (p=0.75). In recipients with graft survival >6 months, DDLTs had a slower decline in eGFR as compared to LDLTs (p<0.01). Amongst LDLTs the decline in eGFR continued over the entire 10-year period, whereas amongst DDLTs, the decline in eGFR slowed significantly after 6-months (p=0.01). This difference between the two groups was not seen amongst patients in the highest quartile of baseline eGFR. Patient and graft survival was similar. In conclusion, the incidence of end stage renal disease was similar in both DDLT and LDLT patients but LDLT recipients seem to have a more sustained decline in eGFR when compared to DDLT recipients.This article is protected by copyright. All rights reserved.
... No significant difference in outcome could be identified between both types of grafts. The results from LDLT appear to show good long term survival rates with retrospective studies showing comparable rates to OLT [82,86,87] . Some other retrospective studies showed a higher rate of tumor recurrence with LDLT than with conventional OLT [81,83,84] . ...
Liver transplantation as a management of hepatocellular carcinoma
Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.
Liver transplantation (LT) is a life-saving and evidence-based intervention for patients with acute liver failure and chronic end-stage liver disease. Significant progress has been made in advancing pre-LT management, transplant techniques, post-LT long-term care, and immunosuppression regimes. However, as rates of DC continue to increase, causes of liver disease and indications for LT continue to be investigated to ensure equity and further improve liver allocation models, waitlist outcomes, and post-LT outcomes for all patient populations.
The use of hepatitis C virus (HCV) -positive organs in HCV-negative recipients with posttransplant antiviral treatment has increasingly been studied since the introduction of new direct-acting antivirals. This article reviews existing experience in liver and kidney transplant. Fifteen studies with 218 HCV D+/R- liver transplants, with 182 from viremic donors, show a sustained viral response for 12 weeks (SVR12) rate of 99.5%. Nine studies involving 204 HCV donor-positive recipient-negative kidney transplant recipients had an SVR12 rate of 99.5%. Complications are infrequent. Preemptive treatment in kidney transplant of for only 4 weeks or even 4 days showed surprising success rates.
Purpose of review:
This article will summarize prior and recent studies comparing outcomes between living donor and deceased donor liver transplantation (LT) in adults and provide a rationale and framework for expanding living donor liver transplantation (LDLT) in Western countries to address the growing critical organ shortage.
Recent findings:
There is a growing body of evidence demonstrating superior survival outcomes in LDLT in addition to a multitude of other advantages including shorter cold ischemia times, opportunity for pretransplant medical optimization, and expansion of transplant eligibility. Additionally, these outcomes continue to improve with center volume and experience.
Summary:
LDLT in adults emerged in response to an effective donor organ shortage created by the critical discrepancy between donor graft supply and demand. Overcoming this organ shortage and an increasing waitlist mortality requires a liver transplant framework that fully integrates LDLT into liver disease management although continuing to fully maximize deceased donor graft utilization at experience, capable centers. Optimizing both living and deceased donor graft utilization will drastically increase patients' access to LT.
Background:
There has been a recent increase in enthusiasm for expansion of living donor liver transplantation (LDLT) programs.
Methods:
Using all adults initially placed on the waiting list in the US, we estimated the risk of overall mortality under national strategies which differed in their utilization of LDLT. We used a generalization of inverse probability weighting which can estimate the effect of interventions in the setting of finite resources.
Results:
From 2005 to 2015, 93,812 eligible individuals were added to the waitlist - 51,322 received deceased donor grafts while 1,970 underwent LDLT. Individuals who underwent LDLT had more favourable prognostic factors, including lower mean MELD score at transplant (14.6 vs 20.5). The 1-year, 5-year, and 10-year cumulative incidence of death under the current level of LDLT utilization were 18.0% (95% CI: 17.8, 18.3%), 41.2% (95% CI: 40.8, 41.5%), and 57.4% (95% CI: 56.9, 57.9%) compared to 17.9% (95% CI: 17.7, 18.2%), 40.6% (95% CI: 40.2, 40.9%), and 56.4% (95% CI: 55.8, 56.9%) under a strategy which doubles LDLT utilization.
Conclusion:
Expansion of LDLT utilization would have a measurable, modest effect on the risk of mortality for the entire cohort of individuals who begin on the transplant waiting list.
Purpose of review:
Application of living donor liver transplantation (LDLT) in model for end-stage liver disease (MELD) 35+ patients has been regarded with skepticism. There is concern that a partial graft may not achieve favourable outcomes, and that a healthy donor is risked for a transplant which might turn out to be futile.
Recent findings:
In practice, LDLT improves access to liver graft and allows timely transplantation. Long-term results from high-volume centres revealed that outcomes of LDLT in these patients have not been jeopardized by limited graft volumes. With unimpeded vascular outflow, a partial graft could provide sufficient function to overcome the stress of transplant operation. However, LDLT is a complex operation with immense technical demand. A steep learning curve is encountered before optimal outcomes could be produced. Meanwhile, donor safety remains the paramount concern. Donor should not be evaluated for futile candidates. MELD 35+ patients with refractory sepsis or cardiac event are unlikely to benefit from liver transplantation. Borderline donors, in terms of donor safety or graft quality, should not be accepted. As in recipient operation, accumulation of experience is crucial to reduce donor mortality and morbidity.
Summary:
LDLT is justified for MELD 35+ in high-volume centres with vast experience. Satisfactory recipient outcomes can be produced with minimal donor morbidity.
Introduction:
Interferon (IFN) treatment for liver transplant (LT) recipients with hepatitis C virus (HCV) increases acute cellular rejection (ACR), and worsens graft and patient survival. It is unknown if direct acting antivirals (DAA) affect rejection rates or post-transplant survival.
Method:
UNOS STAR files of December 2017 (n=25916) were analyzed.
Results:
Compared to Non-HCV-LT, HCV-LT survival was worse in the IFN-era (2007-2008) and IFN+DAA-era (2011), but not in the DAA-era (2014-2015). ACR6m rate has been less frequent in newer eras, and was lower in HCV-LT than in Non-HCV-LT in both the DAA-era (6.9% versus 9.3%, p<0.001) and in the IFN+DAA-era (8.8% versus 11.8%, p=0.001), but not in IFN-era (10.8% versus 11.0%, p=0.39). HCV-LT recipients who had ACR6m had worse 2-year survival than those without ACR6m, in the IFN-era (80.0% versus 88.4%, p<0.0001) and in IFN+DAA-era (81.4% versus 89.2%, p<0.01) but not in the DAA-era (90.4% versus 93.2%, p=0.085). Cox proportional hazard model identified ACR6m as independent risk factor for mortality in HCV-LT in IFN-era (HR=1.88, p=<0.001) and in IFN+DAA-era (HR=1.84 p=0.005), but not in DAA-era (p=n.s.).
Conclusions:
Two-year survival of HCV-LT recipients were significantly better in DAA-era: these were associated with reduced rate and impact of ACR6m. This article is protected by copyright. All rights reserved.
Background
Graft and patient survival outcomes following split liver transplantation (SLT), living‐donor liver transplantation (LDLT), and deceased‐donor liver transplantation (DDLT) were estimated using Bayesian network meta‐analysis.
Methods
Databases were searched for relevant articles over the previous 20 years (MEDLINE, Embase, Cochrane Library, and Google Scholar). Systematic review, pair‐wise meta‐analysis, and Bayesian network meta‐analysis were performed.
Results
Pairwise meta‐analysis demonstrated that there were no significant differences in graft and patient survival outcomes. Consequently, Bayesian network meta‐analysis demonstrated no significant differences in 1, 3, and 5‐year graft and patient survival between the three alternative liver transplantations. No discrepancies were demonstrated after comparisons of direct and indirect evidence of 1, 3, and 5‐year patient and graft survival of the three node‐split models namely: SLT, LDLT, and DDLT.
Conclusions
The 1, 3, and 5‐year graft and patient survival of the SLT and LDLT cohorts compared to the DDLT cohort demonstrated no significant differences. The direct and indirect evidence of the present study can serve as comparator for future studies.
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This article reviews the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). The findings show that the number of adult-to-adult living donor liver transplants is consistently increasing. Living donor liver transplantation has an important benefit for patients with acute liver failure, does not compromise donor safety, and has lower rates of acute cellular rejection in biologically related donor and recipient. The conclusions from the A2ALL consortium have been critical in transplant advancement, supporting increased use to help decrease waitlist death and improve long-term survival of transplant recipients.
Background and aims:
Patients with end-stage liver disease show sarcopenia, and the preoperative sarcopenia is independently associated with patient mortality after liver transplantation. However, few studies have examined the relationship between perioperative loss of core muscle and patient mortality in living donor liver transplantation (LDLT). This study was performed to investigate the association between a perioperative decrease in the psoas muscle index (PMI) and patient mortality after LDLT.
Methods:
Adult patients (age ≥ 18 years) undergoing LDLT between January 2009 and December 2016 were classified into low-loss (> 25th quartile) vs. high-loss (≤ 25th quartile) groups according to PMI change between the day before surgery and postoperative day (POD) 7. Patient survival was compared between the two groups and factors affecting survival were analyzed.
Results:
The median (interquartile) level of PMI change from the day before surgery to POD 7 was -4.8% (-11.7% to 1.2%). Although there was no preoperative difference in PMI between the low and high-loss groups, patients with PMI change ≤ -11.7% showed poorer survival than those with PMI change > -11.7% during the follow-up period. A PMI decrease ≤ -11.7% between the day before surgery and POD 7 is an independent predictor of patient mortality after LDLT. In addition, intraoperative packed red blood cell transfusion, graft fat percentage, and reoperation and infection after surgery were significantly associated with patient mortality.
Conclusions:
A PMI decrease ≤ -11.7% between the day before surgery and POD 7 is an independent predictor of patient mortality after LDLT. It is necessary to identify the factors responsible for the perioperative decrease in skeletal muscle mass and ascertain if they are modifiable to improve patient survival after LDLT. This article is protected by copyright. All rights reserved.
Background:
Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared to deceased donor liver transplant (DDLT). This has been assumed to be due to the frequent use of small-for-size grafts (SFSG) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSG on the oncologic outcomes of patients with HCC who underwent LDLT.
Methods:
Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched to 1 (graft-to-recipient body weight ratio [GRWR] <0.8%): 3 (GRWR≥0.8%) ratio according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR<0.8%.
Results:
Using propensity score matching, 82 patients with GRWR<0.8% and 246 patients with GRWR≥0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P=0.82) and patient survival (P=0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1-, 3-, and 5-year recurrence free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR<0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR≥0.8% (P=0.049). The former group exhibited poor patient survival rates (P=0.047).
Conclusions:
For patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Since extended criteria are frequently used in LDLT for HCC, recipients' prognosis can be improved if liver grafts of appropriate size are carefully selected during donor selection. This article is protected by copyright. All rights reserved.
We modified the previously described DMELD score in deceased donor liver transplant, to (D+10)MELD to account for living donors being about 10 years younger than deceased donors, and tested it on living donor liver transplantation (LDLT) recipients. 500 consecutive LDLT, between July 2010 and December 2012 were retrospectively analyzed to see the effect of (D+10)MELD on patient and graft survival. Donor age alone did not influence survival. Recipients were divided into 6 classes on based on the (D+10)MELD score: Class 1 (0-399), Class 2 (400-799), Class 3 (800-1199), class 4 (1200-1599), Class 5 (1600-1999) and Class 6 (>2000). The one year patient survival (97.1, 88.8, 87.6, 76.9 and 75% across class 1-5, p = 0.03) and graft survival (97.1, 87.9, 82.3, 76.9 and 75%; p=0.04) was significantly different among the classes. The study population was divided into 2 groups at (D+10)MELD cut off at 860. Group 1 had a significantly better 1 year patient (90.4% vs 83.4%; p = 0.02) and graft survival (88.6% vs 80.2%; p = 0.01). While donor age alone does not predict recipient outcome, (D+10)MELD score is a strong predictor of recipient and graft survival, and may help in better recipient/donor selection and matching in LDLT. This article is protected by copyright. All rights reserved.
The high incidence of end-stage organ failure and the inadequate supply of cadaveric organs increases the gap between organ availability and organ demand, resulting in prolonged waiting times, and consequently, elevated mortality on the waiting list. Living donation emerges therefore as a potential source to overcome organ shortage. Donor safety, however, is clearly the major concern in living-donor transplantation, as individuals who are willing to donate are exposed to surgical procedures that pose risks and offer no physical benefits.
While specific benefits for the recipients have been ascertained for some living-related transplantations, in the case of other organs, neither short- nor long-term functional outcomes have proven to be superior to organ transplantation from deceased donors. In critically ill children and in those with end-stage disease, living donation is a feasible option, due to both short- and long-term favorable outcomes.
Careful candidate evaluation and selection, along with periprocedural care by a qualified, expert team are crucial to face the major concerns regarding donor morbidity and mortality.
Various issues of living-related organ transplantation are still under stringent debate, and the future of this procedure will probably depend on the ability to improve physical and psychological donor outcomes, the precise determination of outcomes for specific pathologic entities, the improvement of recipient survival, and the field’s financial growth margin.
Given the small number of living transplantations, apart from living donor kidney transplant, it is preferable to concentrate the performance of these procedures in a few excellent centers, since center experience leads to better results.
The British Transplantation Society Guidelines for Living Donor Liver Transplantation was published in July 2015 and is the first national guideline in the field of living donor liver transplantation. The guideline aims to review the evidence relating to the evaluation process of both recipient and donor candidates; address the moral and ethical issues surrounding the procedure; outline the technical aspects of the procedure, including the middle hepatic vein controversy and the "small for size syndrome"; review donor and recipient outcomes and complications including donor mortality; and examine evidence relating to the advantages and disadvantages of living donor liver transplantation.In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations Assessment, Development and Evaluation system to rate the strength of evidence and recommendations.This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the delivery of living liver donation in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at http://www.bts.org.uk/BTS/Guidelines_Standards/Current/BTS/Guidelines_Standards/Current_Guidelines.aspx?hkey=e285ca32-5920-4613-ac08-fa9fd90915b5.
Chronic hepatitis C (HCV) infection is one of the leading indications for liver transplantation (LT) globally. Hepatitis B virus (HBV) is a common indication for LT in Asia but accounts for less than 10% of LT in the USA and Europe. Both HBV and HCV can cause recurrent disease after LT and the course of hepatitis after LT is accelerated compared to pretransplantation. For HBV, effective prophylactic therapies, including hepatitis B immune globulin and nucleos(t)ide analogues, can prevent recurrent disease in 80% or more of cases and graft survival is excellent. For HCV, there is no effective prophylactic therapy and recurrent disease leading to graft loss occurs in up to 30% within 5°years. Consequently, survival is lower in HCV-infected LT recipients than non-HCV patients. The best strategy to extend graft survival in HCV patients is eradication of HCV infection prior to or after transplantation. Peginterferon and ribavirin, the currently approved therapy for HCV, achieves viral clearance in only 30-40% of treated LT recipients, overall, and tolerability of therapies is a major limitation. Liver transplantation is feasible for HIV-infected patients and cirrhosis secondary to HBV and HCV are the most common indications for LT in these patients. HBV-HIV coinfected LT patients have similar survival to HBV monoinfected patients, whereas survival of HCV-HIV coinfected LT patients is inferior to LT patients with HCV alone.
The scarcity of donor organs is the major limiting factor in liver transplantation. Living donor liver transplant (LDLT) has evolved over last two decades as an alternative to deceased donor transplant in the western world. The primary concern with the development of LDLT remains the potential for mortality and morbidity in the healthy donor. While there is no obvious benefit for the donor, there are survival advantages for recipients of LDLT. Most notable is that waiting times can be reduced, allowing the transplant to be performed before the recipient's health deteriorates. In areas of the world where deceased donor transplants are not performed due to nonexistent deceased donor graft donation, the advantages of LDLT are even more obvious. Despite being technically complex and labor intensive, LDLT has continued to evolve in the recent years leading to increased donor safety and better short term recipient outcomes. But, long term results, both in donor as well as the recipient, need to be better defined.
The first living-donor liver transplantation (LDLT) was performed in 1988. Since then the procedure has been developed especially in Asian countries to alleviate the problem of postmortem organ shortage. Inherent to the LDLT are however its high technical, logistical, and ethical complexities when compared to postmortem donor liver transplantation. A high technical flexibility is required during the allograft procurement as well as during the transplantation procedure especially in case of adult-to-adult liver transplantation. Controversies about the inclusion of the middle hepatic vein in the graft, the necessity of the venous outflow reconstruction as well as the respective role of left or right livers in adult LDLT are still dominating most of the scientific meetings about LDLT; the definitive answer is still out. Without any doubt, LDLT represents a major ethical challenge as the donation procedure has a certain, although low, mortality risk. It is clear that it is of utmost importance to well inform donor as well as recipient about the meaning and the risk of both procedures. A good balance between donor safety and recipient benefit must be carefully evaluated especially in the Western world where this surgery is performed much less frequently than in the Eastern world.
Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the two most common primary hepatic malignancies. Successful and timely surgical management is the only hope for long-term survival. HCC arises in a background of cirrhosis in the majority of patients. Surgical resection of HCC by means of a partial hepatectomy is an adequate treatment when restricted to noncirrhotic patients or to patients with a very early stage of cirrhosis. Liver transplantation is currently the best treatment for patients with HCC and cirrhosis. The best outcomes are obtained when its application is limited to patients with a single tumor less than 5 cm across or three tumors each less than 3 cm. Expansion of these criteria for transplantation is currently under debate. Pretransplant locoregional therapy in the form of radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and percutaneous ethanol injection is indicated in patients awaiting transplantation. TACE and RFA successfully downstage HCC tumors, expanding the transplantability window for these patients. However, these therapies have failed to clearly demonstrate a reproducible benefit in terms of long-term survival or dropout rates from the waiting list. The surgical management of cholangiocarcinoma depends on its location along the biliary tree. Intrahepatic tumors are treated by a partial hepatectomy; distal tumors are treated by a pancreatoduodenectomy. Hilar tumors (the most common location) are best treated by an extended hepatectomy or by liver transplantation when unresectable. Despite continuous improvement in anesthesia, surgery, and oncology the outcomes in the treatment of cholangiocarcinoma remain poor. The addition of pretransplant chemoradiation therapy has remarkably improved the outcome of liver transplantation in the treatment of hilar cholangiocarcinoma. Liver transplantation, although not applicable to most patients with HCC or cholangiocarcinoma, has revolutionized their prognosis offering a greater than 75% chance of survival at 4 years.
The hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death and HCV recurrence still constitute a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and non-responders, is still controversial. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden both in the pre- and in the post- liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated cirrhosis sustain a SVR 12 of 89% [1] but one third of patients do not clinically impoved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if LT is performed at least one month after undetectable HCV-RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 to 90%. In this review we have focused on the evolution of antiviral therapy for HCV recurrence from the "old" interferon-based therapy to the "new" interferon-free regimens, highlighting useful information to aide the transplant hepatologist in the clinical practice. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
The aim of this chapter is to present an up-to-date comprehensive review of pathology, pathophysiology and clinical perspectives related to liver transplantation. It is written for trained pathologists, hepatologists and transplant surgeons who are interested in developing expertise in the field of liver transplantation. Classic and unusual patterns of allograft rejection, recurrent and de novo liver diseases, technical complications, complications of immunosuppression and donor liver evaluation are illustrated in detail and emphasis is placed on biopsy interpretation. This chapter also includes contributions by experienced liver transplant surgeons and hepatologists who share their valuable expertise with pathologists to help pathologists better understand the clinical background and patient management when interpreting allograft biopsies.
Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) has been associated with progression to cirrhosis in ≈20% of patients, 5 years postoperatively. Accelerated decompensation has also been noted when compared with cirrhosis in non-transplant patients. Different treatment strategies are available for recurrent HCV infection post-OLT, but efforts are hindered by the modest response rates, poor tolerability and the risk of rejection as well as graft loss.
Anti-HCV immunoglobulin therapy to prevent graft infection with HCV has no established role at present but studies are ongoing. Treatment prior to transplantation in patients with decompensated cirrhosis has been evaluated but the results are too preliminary to make firm recommendations. Prophylactic interferon-based antiviral therapy in the early postoperative period to prevent graft infection was shown to have low response rates and high rates of adverse effects. Treatment of established recurrent HCV infection with combination peginterferon (pegylated interferon) and ribavirin is associated with 10–59% sustained virological response and the predictive value of a positive early virological response has been validated in the post-transplant setting. Improvement in inflammatory activity after viral eradication is well established, but fibrosis regression or stabilisation is less predictable and factors such as rejection and biliary complications may still contribute to graft loss. Most studies have initiated therapy at least 6 months postoperatively in order to optimise patient tolerance and enable the addition of ribavirin. The use of adjuvant agents to treat drug-induced neutropenia and anaemia in this population is evolving and becoming a crucial part of therapy. Determination of optimal doses of both pegylated interferon and ribavirin, and guidance on when to stop treatment, as well as improving tolerability are important steps in achieving higher response rates and minimising drug toxicity.
Regeneration of the partial allograft and the growth of children may cause kinking of the bile outflow tract after pediatric living donor liver transplantation (LDLT), but bile duct kinking after adult LDLT is rarely reported. We herein present our experience with treatments of two patients who suffered from anastomotic strictures caused by severe bile duct kinking after LDLT. The first patient was a 57-year-old woman with hepatitis B virus (HBV)-related liver cirrhosis, who developed a biliary stricture 5 months after receiving a right-lobe LDLT. Subsequently, endoscopic and percutaneous treatments were attempted, but they both failed to solve the problem. The second was a 44-year-old woman, and she also had HBV-related liver cirrhosis. A biliary stricture occurred 14 months after LDLT. Likewise, the guide wire failed to pass through the stricture site when endoscopic interventions were conducted. Afterwards, both of the two cases underwent reexploration. It was observed that compensatory hypertrophy of the allografts resulted in kinking and sharp angulation of the bile ducts, and the anastomotic sites were found to be severely stenotic. Finally, re-anastomosis by Roux-en-Y procedure was successfully performed, and long-term stenosis-free survival was achieved in both of them. Our experience suggests that bile duct kinking after LDLT may play a role in the high incidence of anastomotic strictures in adult LDLT recipients, which may also result in the treatment failure of the non-surgical techniques for anastomotic strictures. Re-anastomosis in the form of Roux-en-Y hepaticojejunostomy is an effective surgical option for the treatment of such a condition.
This article is protected by copyright. All rights reserved.
Hepatitis C infection is the most common cause of cirrhosis worldwide. Management of chronic hepatitis C in peri-transplant period is challenging. Patients with compensated/Child's A cirrhosis due to hepatitis C virus (HCV) infection are treated like noncirrhotics, with peginterferon (PEG-IFN) and ribavirin, albeit with a higher incidence of complications. Treatment is not recommended for decompensated cirrhotics due to higher complication rate including the risk of death. After liver transplant, immunosuppression should be adjusted to prevent/delay recurrent HCV disease. Incidence and severity of recurrent HCV disease as well as patient and graft survival is similar between living donor and deceased donor liver transplants. It is currently recommended to treat established recurrent hepatitis C, that is raised alanine aminotransferase (ALT) with HAI >4 and/or F >1. Pre-emptive/prophylactic antiviral therapy is poorly tolerated and has low efficacy. Standard dose regimen (PEG-IFN 1.5 μg/Kg or 180 μg weekly + ribavirin 800–1200 mg/day) for 48 weeks irrespective of the genotype is the recommended treatment protocol. Therapy poses significant problems in the form of anemia, neutropenia, higher risk of rejection, and so on.
The number of patients needing liver transplantation greatly exceeds the number of organs that can be obtained from cadavers. Living-donor liver transplantation has therefore received increasing attention. A total of 509 such procedures were performed in 2001. The procedure involves the transplantation of the right hepatic lobe of the donor into the recipient after the removal of the entire diseased liver. In coming years, the role of this procedure will be determined by weighing the risk to donors against the improvement in outcome for recipients.
The transplantation of the right lobe of a liver from a living adult donor into an adult recipient has been performed increasingly frequently in the United States. Although the use of grafts from living donors is standard practice in transplantation in children, their use in adults remains controversial.
To study the use of liver transplantation from a living donor, we sent a 24-item questionnaire to all liver-transplantation programs in the United States. Data on indications, evaluation, and outcomes were analyzed with the use of univariate and multivariate methods. Data on recent transplantations were gathered from the Scientific Registry of Transplant Recipients and directly from the transplantation programs.
Questionnaires were returned by 84 of the 122 programs (69 percent) describing the results of 449 adult-to-adult transplantations of partial livers from living donors that were performed in 42 centers. Fourteen centers had performed more than 10 such transplantations each and together accounted for 80 percent of such transplantations. Centers that performed such transplantations also performed more transplantations of livers from cadaveric donors and more transplantations from living donors in children than centers that did not perform the adult-to-adult procedure (P=0.002 and P=0.001, respectively). A total of 45 percent of potential donors who were evaluated eventually donated a lobe of their liver; 99 percent of these donors were genetically or emotionally related to the recipient. Complications in the donor were more frequent in the centers performing the fewest transplantations from living donors in adults and included biliary complications requiring intervention (in 6.0 percent), reoperation (in 4.5 percent), and death (in one donor [0.2 percent]). Among the recipients, 1.6 percent did not meet criteria for receipt of a cadaveric transplant; cancer, retransplantation, and acute liver failure were uncommon indications for transplantation from a living donor. Biliary complications occurred in 22.0 percent of recipients, and vascular complications occurred in 9.8 percent.
Adult-to-adult liver transplantation from a living donor is increasingly performed in the United States but is concentrated in a few large-volume centers. Mortality among donors is low, but complications in the donor are relatively common.
Living donor transplantation in children has proven to be safe and effective for both donors and recipients and has helped make death on the waiting list a less common event. Since its introduction in 1990, many of the technical and ethical issues have been addressed, and the procedure is generally applied. The development of left or right hepatic lobectomy for adult-to-adult living donor liver transplantation has been slower. Because of the ongoing shortage of cadaver livers suitable for transplantation, adult-to-adult living donor liver transplantation has been performed at a number of centers. Although early results appear encouraging, sufficient data are not available to ascertain donor morbidity and mortality rates. There is general consensus that the health and safety of the donor is and must remain central to living organ donation. The practice guidelines put forth here are intended to underscore this issue, as well as provide a mechanism to document outcomes as the area develops.
An increasing number of transplant centers are performing adult living donor liver transplantation (LDLT). We evaluated peoples' perspectives on possible outcomes of living donation, thresholds for donating, and views regarding the donation process. One hundred fifty people were surveyed; half were from a medical care group serving an indigent population and half were from a private clinic. Preferences about outcomes of adult living donation were ranked and quantified on a visual analogue scale. Thresholds for donation to a loved one were quantified. Sixty percent of the respondents suggested they would prefer to donate and die and have the transplant recipient live rather than forego donation and have the potential transplant recipient die of liver failure. Participants' stated threshold for living donation was a median survival for themselves of only 79%. They would require that their loved one have a median survival of 55% with transplantation before they would agree to donate. Respondents from the medical care group reported higher survival thresholds for themselves and the transplant recipient, and race was the most statistically significant predictor of those thresholds. Sex was more predictive of threshold probabilities from the private clinic. Eighty-one percent of the respondents believed that the potential donor, not a physician, should have the final say regarding candidacy for living donation. In conclusion, the findings of this survey support the use of adult LDLT. Most respondents were willing to accept mortality rates that far exceed the estimated risk of donation and favored outcomes in which a loved one was saved.
Despite the increasing use of living donor liver transplantation, little is known about donor needs, concerns, and experiences. The goal of this study is to assess morbidity associated with living donation from a donor perspective, functional status after donation, and overall satisfaction with the donation process. We surveyed all living donors (LDs) from our center. Demographics, perioperative experience, and satisfaction with donation were assessed. The Medical Outcomes Study 12-Item Short-Form Survey (SF-12), a well-validated tool, measured overall health-related quality of life. Of 27 subjects eligible for the study, 27 subjects (100%) participated. Forty percent reported an event they deemed an immediate complication, of which 60% were recorded in the medical record. Complications requiring readmission were reported by 22%. Mean recovery time was 12 weeks (range, 1 to 52 weeks). No significant change was reported in physical activity, social activity, or emotional stability, and 92% of donors resumed their predonation occupation. Regardless of recipient outcome, 100% of donors would donate again and recommend donation to someone in contemplation. All surveyed LDs at our institution are satisfied with their donation decision. Morbidity in the first year after donation may be greater than previously appreciated. Despite complications, postoperative functional status of donors is equal to or better than population norms.
The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV.
Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics.
Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70).
HCV infection significantly impairs patient and allograft survival after liver transplantation.
This article has no abstract; the first 100 words appear below.
Living donors have participated in solid-organ transplantation throughout the 48 years since Dr. Joseph Murray successfully performed kidney transplantation between identical twins. Kidney transplantation from living, unrelated donors is no longer unusual, and some centers allow for anonymous donors or for a donor swap in cases of biologic incompatibility. Surgical advances now permit each of two donors to provide a lobe of lung to a patient with end-stage lung disease from cystic fibrosis. In spite of these advances, it is still not clear exactly how safe it is to donate a large part of one's liver. Altruism is characterized by . . .
Owen S. Surman, M.D.
Massachusetts General Hospital, Boston, MA 02114
Living donor liver transplantation (LDLT) is now widely performed for adult patients to resolve the critical shortage of organs from cadavers. The objective of this study was to analyze the experience of a single center with adult LDLT.
Eighty-two consecutive LDLT procedures for adults were divided into 3 groups according to the transplant era and the preoperative condition and indications: all patients between 1996 and 1999 (Group 1, n = 30), good-risk patients between 2000 and November 2001 (Group 2, n = 28), and poor-risk patients (Group 3, n = 24). Up to 1999, left liver graft was used for all patients. Thereafter, right liver was selected only for poor-risk patients. Preoperative status, morbidity, hospital duration, and postoperative graft function and survival rate were examined and compared among the groups.
Comparison of groups 1 and 2 revealed a significant difference in the hospital duration and the survival rate. In contrast, the short-term surgical results were comparable between groups 2 and 3. The 2-year survival rates were 84%, 100%, and 88%, respectively.
The present results suggest that our graft selection criteria are acceptable. A small graft can provide satisfactory results when used in good-risk patients and a right liver graft may be beneficial in poor-risk patients.
Living donor liver transplantation allows an increasing number of patients with end-stage liver disease the opportunity for effective treatment in the face of a critical shortage of cadaveric organs. Hepatic steatosis decreases functional graft mass and may contribute to graft dysfunction. Screening liver biopsy allows accurate quantitation of hepatic fat, but is an invasive procedure that is not universally employed in the evaluation of living donors. We studied 100 consecutive prospective right lobe living donors, all evaluated with liver biopsy, imaging studies, and various clinical parameters. The accuracy and predictive value of body mass index (BMI) and imaging were compared with biopsy in determining the amount of hepatic fat. There were no complications to biopsy, with 33% showing some degree of steatosis. BMI correlated only weakly with biopsy, with 73% of overweight (BMI > 25) donors having little or no hepatic fat. Imaging was only 12% sensitive to small amounts (5% to 10%) of fat, with increasing sensitivity to more severe steatosis. Imaging diagnosed steatosis in 2 donors without hepatic fat and failed to identify a candidate denied with biopsy-proven 30% steatosis. Conversely, 9% of candidates with BMIs of 25 or less had 10% or greater steatosis. Moreover, three candidates were denied surgery because biopsy detected occult liver disease. Accurate quantification of hepatic fat is not afforded by BMI and imaging studies alone. Screening liver biopsy has a low complication rate and may serve to increase donor safety. Biopsy is essential in identifying donor grafts at risk for poor recipient outcome while maximizing the donor pool.
Reliable models that could predict outcome of liver transplantation (LT) may guide physicians to advise their patients of immediate and late survival chances and may help them to optimize organ use. The objective of this study was to develop user-friendly models to predict short and long-term mortality after LT in adults based on pre-LT recipient characteristics. The United Network for Organ Sharing (UNOS) transplant registry (n = 38,876) from 1987 to 2001 was used to develop and validate the model. Two thirds of patients were randomized to develop the model (the modeling group), and the remaining third was randomized to cross-validate (the cross-validation group) it. Three separate models, using multivariate logistic regression analysis, were created and validated to predict survival at 1 month, 1 year, and 5 years. Using the total severity scores of patients in the modeling group, a predictive model then was created, and the predicted probability of death as a function of total score then was compared in the cross-validation group. The independent variables that were found to be very significant for 1 month and 1 year survival were age, body mass index (BMI), UNOS status 1, etiology, serum bilirubin (for 1 month and 1 year only), creatinine, and race (only for 5 years). The actual deaths in the cross-validation group followed very closely the predicted survival graph. The chi-squared goodness-of-fit test confirmed that the model could predict mortality reliably at 1 month, 1 year, and 5 years. We have developed and validated user-friendly models that could reliably predict short-term and long-term survival after LT.
It is not known whether the outcome of liver retransplantation (re-LT) is dependent on the indication for re-LT or cause of liver disease. In this study, our aim is to compare the outcome of re-LT in adults with that of primary liver transplantation (PLT) and determine whether the outcome of re-LT is dependent on its indication. United Network for Organ Sharing data from 1988 to 2001 were used for the study. Of 34,267 patients who met our inclusion criteria, 761 patients underwent re-LT for primary graft nonfunction (PGNF; group 1), 3,428 patients underwent re-LT for other reasons (group 2), and 30,078 patients underwent PLT (group 3). There was a greater incidence of PGNF (9.4% v 4.0%; P <.001) and regrafting (23.1% v 7.4%; P <.001) in the re-LT groups compared with the PLT group. Kaplan-Meier analysis and Cox regression analysis, after adjusting for confounding risk factors, showed significantly lower short- and long-term patient and graft survival in the re-LT groups compared with the PLT group. Kaplan-Meier survival showed lower patient and graft survival in group 1 compared with group 2. However, only graft, not patient, survival was lower in group 1 by Cox regression analysis when adjusted for other risk factors. Patients with hepatitis C virus (HCV) infection who underwent re-LT had lower patient and graft survival compared with those without HCV infection, and HCV was an independent predictor of mortality after re-LT. Re-LT was associated with a greater rate of complications and lower patient and graft survival compared with PLT. Re-LT for PGNF and HCV infection was associated with lower patient and graft survival compared with re-LT for other causes.
Living donor liver transplantation
- Broering DC
- Sterneck M
- Rogiers X
Position paper on adult-to-adult living donor liver transplantation. American Society of Transplant Surgeons: Ethics Committee
Position paper on adult-to-adult living donor liver transplantation. American Society of Transplant Surgeons: Ethics Committee. Liver Transpl 2000;6:815 -817.