The Risk of End‐Stage Renal Disease Among Living Donor Liver Transplant Recipients in the United States

Since initiation of model for end‐stage liver disease (MELD)‐based allocation for liver transplantation, the risk of posttransplant end‐stage renal disease (ESRD) has increased. Recent US data have demonstrated comparable, if not superior survival, among recipients of living donor liver transplants (LDLT) when compared to deceased donor liver transplant (DDLT) recipients. However, little is known about the incidence of ESRD post‐LDLT. We analyzed linked Scientific Registry of Transplant Recipients (SRTR) and US Renal Data System (USRDS) data of first‐time liver‐alone transplant recipients from February 27, 2002 to March 1, 2011, and restricted the cohort to recipients with a laboratory MELD score ≤25 not on dialysis prior to transplantation, in order to evaluate the incidence of ESRD post‐LDLT, and to compare the incidence among LDLT versus DDLT recipients. There were 28 707 DDLT and 1917 LDLT recipients included in the analyses. The 1‐, 3‐ and 5‐year unadjusted risk of ESRD was 1.7%, 2.9% and 3.4% in LDLT recipients, compared with 1.5%, 3.0% and 4.8% in DDLT recipients (p > 0.05), respectively. In multivariable competing risk Cox regression models, there was no association between receiving an LDLT and risk of ESRD (sub‐hazard ratio: 0.99, 95% CI: 0.77–1.26, p = 0.92). In conclusion, the incidence of ESRD post‐LDLT in the United States is low, and there are no significant differences among LDLT and DDLT recipients with MELD scores ≤25 at transplantation.     

When Living Donor Liver Allografts Fail: Exploring the Outcomes of Retransplantation Using Deceased Donors

Outcomes of retransplantation after initial living donor liver transplantation (LDLT) are poorly understood. The aim of this study is to better understand the indications, timing, and outcomes of retransplantation after initial LDLT when compared to after initial deceased donor transplantation (DDLT). From 2002 to 2013, 209 retransplant recipients after initial LDLT and 2893 after initial DDLT were identified in Organ Procurement and Transplantation Network/United Network for Organ Sharing. Multivariable logistic models evaluated the association between initial transplant type and 1‐year mortality. The most frequent reason for early graft failure (≤14 days) in LDLT recipients was vascular thrombosis (63.6%) versus primary graft failure in initial DDLT recipients (59.1%). LDLT recipients were more often acutely and/or critically ill with a greater proportion of Status 1 (42.6% vs. 27.3%; p < 0.001) and intensive care unit (52.2% vs. 39.9%; p = 0.001) recipients at the time of retransplantation. There was no difference in adjusted 1‐year mortality between retransplant recipients after initial LDLT versus DDLT (odds ratio 0.74; 95% confidence interval 0.51–1.08). The proportion of recipients who ultimately required retransplantation for a third time was not different between the two groups (4.8%). Retransplantation outcomes after LDLT are not different from other retransplant procedures, despite recipients having greater acuity of illness and different indications.     

Resource Utilization of Living Donor Versus Deceased Donor Liver Transplantation Is Similar at an Experienced Transplant Center

Although living donor liver transplantation (LDLT) has been shown to decrease waiting-list mortality, little is known of its financial impact relative to deceased donor liver transplantation (DDLT). We performed a retrospective cohort study of the comprehensive resource utilization, using financial charges as a surrogate measure—from the pretransplant through the posttransplant periods—of 489 adult liver transplants (LDLT n = 86; DDLT n = 403) between January 1, 2000, through December 31, 2006, at a single center with substantial experience in LDLT. Baseline characteristics differed between LDLT versus DDLT with regards to age at transplantation (p = 0.02), male gender (p < 0.01), percentage Caucasians (p < 0.01) and transplant model for end-stage liver disease (MELD) score (p < 0.01). In univariate analysis, there was a trend toward decreased total transplant charges with LDLT (p = 0.06), despite increased surgical charges associated with LDLT (p < 0.01). After adjustment for the covariates that were associated with financial charges, there was no significant difference in total transplant charges (p = 0.82). MELD score at transplant was the strongest driver of resource utilization. We conclude that at an experienced transplant center, LDLT imposes a similar overall financial burden than DDLT, despite the increased complexity of living donor surgery and the addition of the costs of the living donor. We speculate that LDLT optimizes transplantation by transplanting healthier and younger recipients.     

Donor‐Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor‐specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA.     

Recipient Morbidity After Living and Deceased Donor Liver Transplantation: Findings from the A2ALL Retrospective Cohort Study†

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two‐fold higher when centers had performed ≤20 LDLT (vs. >40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.     

Outcomes of Living Versus Deceased Donor Liver Transplantation for Acute Liver Failure in the United States

Clinical outcomes for living donor liver transplantation (LDLT) for acute liver failure (ALF) in the United States remain to be determined. To address this gap in knowledge, we examined post–liver transplantation outcomes of adults with ALF undergoing LDLT and deceased donor liver transplantation (DDLT) in the United States. We analyzed Organ and Procurement and Transplantation Network data for adults with ALF who were listed for liver transplantation as status 1 or 1A and who underwent LDLT (N = 21) or DDLT (N = 2316) between October 1987 and April 2011. We found no strong evidence that the survival probabilities for adults with ALF who underwent LDLT were inferior to those who underwent DDLT (P = .764). In adults with ALF who underwent LDLT, 1- and 5-year survival probabilities were both 71%; for DDLT these probabilities were 79% and 71%, respectively. In adults with ALF, 1- and 5-year liver graft survival probabilities, respectively, were 62% and 57% for LDLT, and 74% and 66% for DDLT. In these series of adults with ALF who were listed as status 1 or 1A, patient and graft survival rates for LDLT were similar to those for DDLT. Our findings suggest that if deceased donor livers are unavailable, LDLT is an acceptable option in experienced centers for adults with ALF.     

Reduced Mortality with Right-Lobe Living Donor Compared to Deceased-Donor Liver Transplantation When Analyzed from the Time of Listing

Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end-stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty-four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end-stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1-year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT.     

Survival following right lobe split graft,living‐ and deceased‐donor liver transplantation in adult patients: a systematic review and network meta‐analysis

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. Databases were searched for relevant articles over the previous 20 years (MEDLINE, Embase, Cochrane Library and Google Scholar). Systematic review, pairwise meta‐analysis and Bayesian network meta‐analysis were performed. 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. 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 this study can serve as comparator for future studies.     

Living donor versus deceased donor liver transplantation: a surgeon‐matched comparison of recipient morbidity and outcomes

Informed consent for living donor liver transplantation (LDLT) requires that patients are provided with accurate information on the relative benefits and risks of this procedure compared with deceased donor liver transplantation (DDLT). There is strong evidence to suggest that LDLT facilitates timely transplantation to patients; however, information on the relative morbidity and death risks after LDLT as compared with DDLT is limited. A matched cohort comparison was performed matching recipients for age, MELD, date of transplant, gender, primary diagnosis, and recipient surgeon. A total of 145 LDLT were matched with 145 DDLT. LDLT had a higher overall rate of perioperative surgical complications (P = 0.009). Most of this difference was caused by a higher rate of biliary complications. However, the complications that occurred in the DDLT group tended to be more serious (P = 0.037), and these complications were strongly associated with graft loss in multivariate analysis. The 3‐ and 5‐year graft and patient survivals were similar. In conclusion, DDLT and LDLT have different complication profiles, but comparable hospital stays and survival rates. In areas of deceased donor organ shortages, LDLT offers an excellent alternative to DDLT because it facilitates access to a liver transplant without compromising short‐ or medium‐term recipient outcomes.     

Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation‡

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult‐to‐adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow‐up was 778 and 713 days, respectively. Rates of clinically treated and biopsy‐proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ≥1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ≥1 biopsy‐proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy‐proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Long‐Term Outcomes of Pediatric Living Donor Liver Transplantation in Japan: An Analysis of More Than 2200 Cases Listed in the Registry of the Japanese Liver Transplantation Society

The Japanese Liver Transplantation Society (JLTS) was established in 1980 in order to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed the comprehensive factors that may influence the outcomes of pediatric patients who undergo living donor liver transplantation (LDLT) by evaluating the largest cohort in the world. Between November 1989 and December 2010, 2224 pediatric patients underwent LDLT in Japan. There were 998 male (44.9%) and 1226 female donors (55.1%) without donor mortalities related to transplant surgery. There were 946 male (42.5%) and 1278 female (57.5%) recipients with a median age of 4.0 years (range: 13 days to 17.9 years). Cholestatic liver disease was the leading indication for LDLT (n = 1649; 76.2%), followed by metabolic disorders (n = 194; 8.7%), acute liver failure (n = 192; 8.6%) and neoplastic liver disease (n = 66; 3.0%). The 1‐, 5‐, 10‐ and 20‐year patient survival rates were 88.3%, 85.4%, 82.8% and 79.6%, respectively. Blood‐type incompatibility, recipient age, etiology of liver disease and transplant era were found to be significant predictors of overall survival. We are able to achieve satisfactory long‐term pediatric patient survival outcomes in the JLTS series without compromising the living donors.     

Clinical analysis of emergency liver transplantation: the role of living donor liver transplantation

The current liver allocation system requires reevaluation because of the advancements in peri‐transplantation care and surgical techniques. And, the role of living donor liver transplantation (LDLT) in an emergency has not been determined yet. Retrospective review of all patients undergoing emergency liver transplantation (LT) from January 2000 to June 2010 was conducted, and clinical data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver, and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT). The overall hospital mortality was 21.7% (15/69). The leading cause of death after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that a model for end‐stage liver disease (MELD) >33 [hazard ratio (HR), 16.6; 95% confidence interval (CI), 1.443–191.632; p = 0.024] and existence of pre‐transplantation intubation (HR, 18.2; 95% CI, 1.463–225.483; p = 0.024) were independent factors associated with poor survival after emergency LT. LDLT group and DDLT group showed no difference in hospital mortality (p = 0.854) and graft survival (p = 0.861). Thus, MELD score and respiratory insufficiency could be parameters predicting post‐transplant survival. And, LDLT using the right liver could be an appropriate alternative to DDLT in an emergency.     

Hepatocellular Carcinoma Recurrence and Death Following Living and Deceased Donor Liver Transplantation

We examined mortality and recurrence of hepatocellular carcinoma (HCC) among 106 transplant candidates with cirrhosis and HCC who had a potential living donor evaluated between January 1998 and February 2003 at the nine centers participating in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Cox regression models were fitted to compare time from donor evaluation and time from transplant to death or HCC recurrence between 58 living donor liver transplant (LDLT) and 34 deceased donor liver transplant (DDLT) recipients. Mean age and calculated Model for End-Stage Liver Disease (MELD) scores at transplant were similar between LDLT and DDLT recipients (age: 55 vs. 52 years, p = 0.21; MELD: 13 vs. 15, p = 0.08). Relative to DDLT recipients, LDLT recipients had a shorter time from listing to transplant (mean 160 vs. 469 days, p < 0.0001) and a higher rate of HCC recurrence within 3 years than DDLT recipients (29% vs. 0%, p = 0.002), but there was no difference in mortality or the combined outcome of mortality or recurrence. LDLT recipients had lower relative mortality risk than patients who did not undergo LDLT after the center had more experience (p = 0.03). Enthusiasm for LDLT as HCC treatment is dampened by higher HCC recurrence compared to DDLT.     

Donor BMI >30 Is Not a Contraindication for Live Liver Donation

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right‐lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo‐Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo‐Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.     

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single‐Center Experience

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.     

活体肝移植治疗原发性肝癌的疗效分析

目的 通过活体肝移植(LDLT)与尸体肝移植(DDLT)治疗原发性肝癌(HCC)的比较,探讨LDLT治疗HCC的疗效.方法 分析2007年1月至2008年12月间我院实施的105例肝癌肝移植手术(其中LDLT38例,DDLT67例)的临床资料和随访结果.结果 LDLT患者1年及3年生存率分别为92.1％及78.9％,...     

Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta‐analysis

Experimental studies suggest that the regenerating liver provides a “fertile field” for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease‐free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta‐analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non‐randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02–2.49; I² = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73–1.27; I² = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.     

Adult living‐related liver donation for acute liver failure: is it ethically appropriate?

Carlisle EM, Angelos P, Siegler M, Testa G. Adult living‐related liver donation for acute liver failure: is it ethically appropriate?
Clin Transplant 2011: 25: 813–820.
© 2011 John Wiley & Sons A/S. Abstract: Acute liver failure (ALF) results in the annual death of approximately 3.5 per million people in the United States. Unfortunately, given the marked shortage of cadaveric liver donations and the ethical questions that plague utilization of living donor liver transplantation (LDLT) for ALF, many patients with ALF die before a liver is allocated to them. In this review, we discuss how the consistent utilization of LDLT for ALF could decrease the mortality rate of ALF. Additionally, we examine a key underlying issue: is LDLT for ALF ethically appropriate?     

Living Donor Liver Transplantation for Acute Liver Failure: A Single Center Experience

Objective

Orthotopic liver transplantation (OLT) is the principal therapy for acute liver failure (ALF). The mortality on the waiting list for deceased donor liver transplantation (DDLT) is high, principally in countries where donation rates are low. Living donor liver transplantation (LDLT) seems an option for the treatment of ALF, although some ethical issues need to be considered. Herein we have evaluated LDLT results among patients with ALF and discussed the ethical aspects of procedures performed in emergency situations.

Patients and Methods

From March 2002 to October 2008, we performed 301 liver transplantations, including 103 from living donors. ALF was responsible for 10.6% of all transplantations; LDLT was only considered for pediatric recipients among whom 7 children displayed ALF.

Results

One patient died on postoperative day 33 due to hepatic artery thrombosis. One patient died at 2 months after transplantation due to biliary sepsis, resulting in an overall survival rate of 71%. The average time for donor discharge was 5 days. No mortality or major complications were observed.

Conclusions

The survival of children with ALF undergoing LDLT was comparable to published data. Furthermore, despite the fact that the available time to prepare the donors was limited, no serious complications were observed in the postoperative period. Thus, using living donors for children with ALF is an effective, safe alternative that can be extremely useful in countries with low donation rates.