Renal allograft function in matched pediatric and adult recipient pairs of the same donor

BACKGROUND: To study the effect of donor age on kidney function, the authors investigated matched pairs from the same kidney donor given to a pediatric or an adult recipient. METHODS: Fifteen matched pairs of an adult and a pediatric patient, selected from the Eurotransplant registry, receiving the renal graft from the same cadaveric donor were selected for analysis of graft function over 7 years. Nine matched pairs were from adult donors (mean age, 40 years; range, 23-60 years) and six from pediatric donors (mean age, 11 years; range, 4-15 years). All recipients had comparable immunosuppression with cyclosporine A, prednisolone, and azathioprine and comparable numbers of acute rejection, cytomegalovirus reactivation, and antihypertensive therapy. Mean age of pediatric and adult recipients at transplantation was 5 years (range, 1-9 years) and 38 years (range, 25-60 years), respectively. RESULTS: The calculated glomerular filtration rate (GFR) corrected to body surface area was not different in adult and pediatric recipients. Initial absolute GFR was significantly lower in pediatric recipients (27 mL/ min; range, 17-38 mL/min) than in adult recipients (54 mL/min; range, 25-74 mL/min) (P <0.05) and remained lower in the following years. Initially, pediatric donor kidneys transplanted into pediatric recipients showed a lower absolute GFR than those transplanted into adults, however, approaching the GFR in adult recipients later. Adult donor kidneys transplanted into pediatric recipients showed a persistently lower absolute GFR in children compared with those transplanted into adult recipients. CONCLUSIONS: The authors conclude that adult donor kidneys in pediatric recipients decrease GFR in the early stages and lack an increase in GFR with growth of the child.     

Split liver transplantation: technique and results

The term split-liver transplantation is defined as the division of a deceased-donor liver into 2 different parts that are separately transplanted into 2 different recipients. Two entities may be identified: the first dividing the liver into the small left lateral segment to be transplanted into a small child and the right lobe to be transplanted into an adult recipient. This is a well-established and standard technique leading to excellent results in experienced centers. The second entity, more recently introduced and less standardized, divides the liver into 2 similarly sized parts, both suitable for transplantation into adults or adult-sized children. This article describes the most relevant aspects of the surgical technique and the results of both types of split liver transplantation based on the author's own experience and a review of the literature. Some aspects of the limitation to the diffusion of these procedures and on a possible future scenario are also discussed.     

Split liver transplantation: an overview

Liver transplantation (OLT) has become the only treatment modality for patients with end-stage liver diseases. Establishment of standard liver transplantation technique, development of better immunosuppressive medications and accumulated experience using them safely, and improvement of intensive care and anesthesia played major role to have current 88%-90% 1-year survival after liver transplantation. As liver transplantations became more successful with the growing experience and development in the field, the increased demand for liver allografts could not match the available supply of donor organs. As a result of this imbalance, each year nearly 3000 patients die in the United States awaiting liver transplantation on the national waiting list. Split liver transplantation (SLT) has been perceived as an important strategy to increase the supply of liver grafts by creating 2 transplants from 1 allograft. The bipartition of a whole liver also carries utmost importance by increasing the available grafts for the pediatric patients, where size-matched whole liver allografts are scarce, leading increased incidence of waiting list mortality in this group.In the common approach of the split liver procedure, liver is divided into a left lateral segment graft (LLS) to be transplanted to a child and a right extended liver lobe graft for an adult recipient. In a technically more challenging variant of this procedure, the principle is to split the liver into 2 hemigrafts and use the left side for a small adult or a teenager and the right for a medium-sized adult patient.Donor selection for splitting, technical expertise in both OLT and hepatobiliary surgery, logistics to decrease total ischemia time, and manpower of the transplantation team are important factors for successful outcomes after SLT. The liver can be split on the back table (ex situ) or in the donor hospital before the donor cross-clamp using in situ splitting technique, which was developed directly from living donor liver transplantation. The most important advantage of in situ splitting is to decrease the total ischemia time and increased the possibility of inter-center sharing. The in situ technique of splitting has other advantages, including evaluation of the viability of segment IV in case of LLS splitting and better control of bleeding from cut surface upon reperfusion on the recipient. Recipient selection for split liver grafts is also crucial for success after SLT.In this review, we aim to summarize the advances that have occurred in SLT. We also discuss anatomic and technical aspects, including both approaches to SLT, which is now considered by many centers to be a routine operation.     

Safety and risk of using pediatric donor livers in adult liver transplantation

Pediatric donor (PD) livers have been allocated to adult transplant recipients in certain situations despite size discrepancies. We compared data on adults (age ≥ 19 years) who underwent primary liver transplantation using livers from either PDs (age < 13 years; n = 70) or adult donors (ADs; age ≥ 19 years; n = 1,051). We also investigated the risk factors and effect of prolonged cholestasis on survival in the PD group. In an attempt to determine the minimal graft volume requirement, we divided the PD group into 2 subgroups based on the ratio of donor liver weight (DLW) to estimated recipient liver weight (ERLW) at 2 different cutoff values: less than 0.4 (n = 5) versus 0.4 or greater (n = 56) and less than 0.5 (n = 21) versus 0.5 or greater (n = 40). The incidence of hepatic artery thrombosis (HAT) was significantly greater in the PD group (12.9%) compared with the AD group (3.8%; P = .0003). Multivariate analysis showed that preoperative prothrombin time of 16 seconds or greater (relative risk, 3.206; P = .0115) and absence of FK506 use as a primary immunosuppressant (relative risk, 4.477; P = .0078) were independent risk factors affecting 1-year graft survival in the PD group. In the PD group, transplant recipients who developed cholestasis (total bilirubin level ≥ 5 mg/dL on postoperative day 7) had longer warm (WITs) and cold ischemic times (CITs). Transplant recipients with a DLW/ERLW less than 0.4 had a trend toward a greater incidence of HAT (40%; P < .06), septicemia (60%), and decreased 1- and 5-year graft survival rates (40% and 20%; P = .08 and .07 v DLW/ERLW of 0.4 or greater, respectively). In conclusion, the use of PD livers for adult recipients was associated with a greater risk for developing HAT. The outcome of small-for-size grafts is more likely to be adversely affected by longer WITs and CITs. The safe limit of graft volume appeared to be a DLW/ERLW of 0.4 or greater. (Liver Transpl 2001;7:41-47.)     

Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation

BACKGROUND: Regeneration of the liver to a predetermined size after resection or transplantation is a well described phenomenon, but the time course over which these events occur has not been well defined. It is not clear how initial liver mass, reperfusion, immunosuppression, or steatosis influence this process. METHODS: Liver regeneration was assessed prospectively by volumetric magnetic resonance imaging (MRI) in living right lobe liver donors and the recipients of these grafts. Imaging was performed at regular intervals through 60 days after resection/transplantation, and liver mass was determined. Liver function tests and synthetic function were monitored throughout the study period in donors and recipients of these grafts as well as recipients of cadaveric grafts. RESULTS: MRI consistently overestimated liver mass by a mean of 45 g (+/-65) (range 10-123). Donor liver mass increased by 101%, 110%, 115%, and 144% at 7, 14, 30, and 60 days after resection, respectively. Recipient liver mass increased by 87,101, 119, and 99% at 7, 14, 30, and 60 days after transplantation, respectively. Steatosis did not influence the degree of regeneration or graft function, nor was there a functional difference between grafts of >1% graft to recipient body weight ratio or <1%. CONCLUSIONS: MRI accurately determines right lobe mass. Most liver regeneration occurs in the 1st week after resection or transplantation, and the time course does not differ significantly in donors or recipients. The mass of the graft or remnant segment affects the duration of the regeneration process, with a smaller initial liver mass prolonging the course. Steatosis of <30% had no bearing on liver function or regeneration and, therefore, should not be an absolute criterion for exclusion of donors. A calculated graft to recipient body weight ratio of 0.8% is adequate for right lobe living donor liver transplantation.     

Donor and recipient outcomes in right lobe adult living donor liver transplantation

Severe donor organ shortage has provided the impetus for adult living donor liver transplantation (ALDLT). Despite rapid implementation and expansion of the procedure, outcome analysis of ALDLT is still incomplete. This study analyzed both donor and recipient outcomes after ALDLT at a single center. ALDLT performed at UCLA between August 1999 and November 2001 were reviewed retrospectively. Twenty recipients (14 men and 6 women) with a mean age of 48.8 ± 9.7 (29 to 66) years underwent right lobe ALDLT. By computed tomograpy (CT), graft/recipient weight ratio (GRWR) was 1.3 ± 0.3 (1 to 2.2). Overall 1-year patient and graft survival rates were 95% and 85%, respectively. One recipient died of heart failure with normal liver function 5 months after transplantation. Three grafts (14%) were lost and all three patients underwent successful cadaveric retransplantation. Complications were classified according to the Clavien grading system with all but 3 recipients encountering at least one complication. Nine (45%) had grade 1 (minor), 10 (50%) had grade 2 (potentially life threatening without residual disease/disability), 3 (14%) had grade 4A (retransplantation) and one grade 4B (death). Right lobectomy for living donation was performed in 20 patients (12 men, 8 women). Residual left lobe volumes were 36 ± 5.3 (23.9 to 47.9)% of total donor liver volume. No donor required intensive care unit admission and median hospital stay was 7.5 (6 to 14) days. One donor was aborted after intraoperative biopsy showed > 50% macrovesicular steatosis. No donor mortality or long-term complications were encountered. Five grade 1 minor complications, by Clavien Classification, occurred in 4 of 20 (20%) donors. ALDLT using right lobe grafts is an effective procedure to expand a severely depleted donor, but is associated with a high complication rate despite good survival outcomes. Continuous standardized reporting of ALDLT outcomes is required to allow successful and safe implementation of the procedure. (Liver Transpl 2002;8:901-909.)     

Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors

HYPOTHESIS: To minimize the incidence of ischemic arterial complications, risk factors should be clearly identified. Knowledge of the predisposing factors for such complications would make possible the institution of strict surveillance protocols that could ensure early detection of complications and so prevent the progression of ischemic damage to graft failure. DESIGN: Retrospective univariate and multivariate analysis. SETTING: University hospital. PATIENTS: Six hundred fifty-three adults who underwent 747 orthotopic liver transplantations. MAIN OUTCOME MEASURES: We used univariate and multivariate analyses to retrospectively assess the role of possible risk factors for early and late HA thrombosis (HAT) and stenosis (HAS), including etiology of liver disease, donor and recipient sex and age (aged < or =60 vs >60 years), cause of donor death, preservation solution, cold ischemic time, previous orthotopic liver transplantation, HA back-table reconstruction, direct arterial anastomosis vs interpositional conduit, experience of the surgeon, intraoperative transfusion requirements, acute rejection, and cytomegalovirus infection. RESULTS: We observed 58 ischemic complications, including 26 early HAT, 13 late HAT, and 19 HAS. Independent predictors of early HAT were donor age greater than 60 years and bench reconstruction of anatomical variants of the HA; of late HAT, arterial anastomosis fashioned using an interpositional graft of donor iliac artery (iliac conduit) and donors who died of cerebrovascular accident; and of HAS, previous orthotopic liver transplantation and cytomegalovirus infection. CONCLUSIONS: Predisposing factors for HAT mostly stem from donor and graft features. Use of iliac conduits should be limited, particularly when using old donors. Frequent screening of the arterial flow to the graft with Doppler ultrasonography is advisable in patients at risk.     

Impact of different cadaveric donor age cut-offs on adult recipient survival after liver transplantation: a single-center analysis

The increase in the number of patients awaiting liver transplantation (OLT) has forced the use of cadaveric donors (CD) with suboptimal characteristics. Of these, donor age is perhaps the most investigated parameter. Although excellent outcomes were observed for OLT using CD aged over 60 years, the European Liver Transplant Registry (ELTR) Group found an increased risk by using CD of more than 55 years. The Italian National Transplant Center has recently assumed that CD age more than 60 years is a potential risk factor for OLT. In this study, a single-center analysis was performed by stratifying CD by three age cut-offs (< or =55 or >55, < or =60 or >60, and < or =65 or >65 years) to evaluate effects on OLT outcome. Although no significant difference in 6-month and 1-year patient or graft survival occurred after stratification for each donor age cut-off, a better survival was observed with OLT performed using livers procured from CD >55 years. A significant increase in cold ischemia time (CIT) was observed among OLT performed with grafts procured from CD < or =55 and < or =65 years (P = .007), and there was an inverse correlation between overall CIT and donor age (R = -0.300; P = .0022). However, no impact on 1-year patient survival was observed by introducing CIT in univariate logistic regression models as well as donor age, recipient age, donor/recipient age ratio, donor/recipient sex mismatch, ELTR diagnostic categories, and UNOS status. The results of this study suggest the suitability of CD of more than 55 years for OLT and the need to further investigate the cut-off value for CIT-related risk.     

Cost prediction in liver transplantation using pretransplant donor and recipient characteristics

BACKGROUND: Liver transplantation is a costly procedure and its cost is likely driven by both donor and recipient factors. Recently, the recipient model for end-stage liver disease (MELD) score has been correlated with increased posttransplant cost; however, other factors have not been identified. We sought to identify if other donor and recipient factors are associated with increased cost. METHODS: One hundred sixty-six liver transplants performed at our center from January 2004 through February 2006 were included in the estimation sample, and the subsequent 75 transplants were used as a validation cohort. To determine whether donor factors influenced cost, two latent class linear regression models were created from the estimation sample: one considering only recipient variables (model A) and a second incorporating both donor and recipient factors (model B). The resultant models were then validated in the second group of patients and compared with the best single-segment linear regression models. RESULTS: Model A predictors include pretransplant intensive care unit (ICU) stay, age x body mass index, and calculated MELD. In model B, significant predictors are calculated MELD, age, age x pretransplant ICU stay, and donor age more than 40 as significant variables. In validation, only model A remained predictive of cost. CONCLUSIONS: Although marginal donor factors are recognized to influence clinical outcome, they did not factor significantly in cost modeling. In addition to MELD, the recipient factors of pretransplant ICU stay, age, and body mass index are pretransplant variables correlated mostly with posttransplant cost across broad populations.     

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.     

Long-term outcome of split liver transplantation using right extended grafts in adulthood: A matched pair analysis

OBJECTIVE: Shortage of suitable organs led to the development of alternative techniques in liver transplantation. Split liver transplantation (SLT) is well established in pediatric patients. SLT is not completely accepted in adult recipients due to potential increased risk of complications. Despite satisfying results of short-term outcome, there is a leak on information of the long-term outcome. Therefore, we compared the outcome after transplantation of the right extended liver lobe with whole liver transplantation (WLT) using a matched pair's analysis. PATIENTS AND METHODS: From the period of January 1993 to February 2005, 70 SLT recipients were matched with 70 WLT recipients of whole livers. Matching criteria were: 1) indication for transplantation, 2) United Network for Organ Sharing (UNOS) status, 3) recipient age, 4) donor age, 5) cold ischemic time, and 6) year of transplantation. The outcome was analyzed retrospectively. RESULTS: Mean follow-up was 36 months. The 2- and 5-year patient survival rates after SLT and WLT were 86.3% and 82.6%, and 78.4% and 75.6%, respectively (log rank, P = 0.2127). Two- and 5-year graft survival rates were 77.3% and 77.3% after SLT and 71.9% and 65.8% after WLT, respectively (log rank, P = 0.3822). The total biliary complication rate was 11.4% in the SLT group versus 10.0% in the WLT group in the short-term course, while it was 8.5% after SLT and 10.0% after WLT in the long-term course. We did not observe significant differences between the groups in term of short- and long-term morbidity. CONCLUSION: Transplantation of the right extended lobe deriving from left lateral splitting of deceased donor livers is followed by the same long-term patient and graft survival, which is known from WLT. There were no differences in the complication rates even in long-term outcome implementing that SLT does not put the adult recipient to an increased early and late risk. Transplantation of the extended right liver lobe provides a safe and efficient procedure in adult patients to expand the number of available grafts.     

Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.     

Temporary auxiliary liver transplantation from a living donor to an adult recipient with familial amyloid polyneuropathy

A 33-year-old patient with familial amyloid polyneuropathy (FAP) underwent temporary auxiliary partial orthotopic liver transplantation (APOLT) from a living donor with a small-for-size graft. The auxiliary left lobar graft, which weighed only 230 g, was orthotopically transplanted after resection of the recipient's left lobe. The right portal vein was transected to induce compensatory hypertrophy of the left lobar graft. Posttransplant computed tomography showed atrophy of the native liver and hypertrophy of the graft, the volume of which had increased to 446 ml by postoperative day 41. The remnant native liver was removed 6 weeks after APOLT, and there were no signs of liver dysfunction during the postoperative course. Our experience with this case suggests that temporary APOLT is the treatment of choice, guaranteeing a sufficient margin of safety for both donor and recipient, in living donor liver transplants for FAP where the donor's left lobe is disproportionately small.     

Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention‐to‐treat principle

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre‐treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention‐to‐treat principle resulted in a better five‐yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five‐yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five‐yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.