Hepatopulmonary syndrome after living donor liver transplantation and deceased donor liver transplantation: a single-center experience.

Hepatopulmonary syndrome (HPS) is a progressive, debilitating complication of end-stage liver disease. In contrast to the well-established reversal of HPS after deceased donor liver transplantation (DDLT), little has been written about the natural course of HPS after the newer procedure of living donor liver transplantation (LDLT). We describe HPS in a small series of 4 liver transplant recipients (2 DDLT; 2 LDLT) at a single center. Before transplantation, these 4 patients had a mean shunt fraction of 23.6 +/- 14.3% and a mean PaO2 of 58.5 +/- 11.3 mm Hg. All 4 patients used supplemental oxygen before transplantation. Sixteen weeks after transplantation, all 4 patients had normalized or improved shunt fraction and PaO2. These patients regained normal pulmonary function within a few months, despite the period of hepatic regeneration after LDLT. In conclusion, both DDLT and LDLT are associated with rapid and dramatic reversal of HPS.     

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: comparable survival and recurrence

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow-up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1-, 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC.     

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.     

Geographic disparities in deceased donor liver transplantation within a single UNOS region.

Although the Model for End-Stage Liver Disease (MELD) scoring system has improved the ability to measure medical urgency for transplantation, geographic disparities in the probability of being delisted as a result of complications of end-stage liver disease or death and in the probability of orthotopic liver transplantation (OLT) remain. The purpose of the current study was to identify factors associated with these variations among donor service areas (DSAs) in one United Network for Organ Sharing (UNOS) region. Data for 2,948 candidates listed for OLT within 4 DSAs in UNOS region 4 between February 2002 and November 2005 were obtained from UNOS. Multivariate regression models were used to identify study factors associated with delisting (due to deterioration or death) and likelihood of OLT. After risk adjustment for candidate characteristics, those listed in DSA-3 and DSA-4 were at significantly higher risk of delisting than candidates listed in DSA-2 (hazard ratio, 1.22 and 1.10 vs. 0.87 for DSA-2; P = 0.01 and 0.05, respectively). In addition, the likelihood of OLT was significantly higher for candidates listed in DSA-1 than in DSA-2, DSA-3 or DSA-4 (hazard ratio, 1.00 compared with 0.45, 0.77, and 0.51; P < 0.001 for all pairwise comparisons). Despite the implementation of the MELD system, great geographic disparities exist in the likelihood of delisting and for OLT, suggesting the need for further refinement in regional allocation strategies.     

Use of living donor liver transplantation varies with the availability of deceased donor liver transplantation

The demographics of patients in the United States who undergo living donor liver transplantation (LDLT) versus patients who undergo deceased donor liver transplantation (DDLT) are interesting with respect to the demographics of the donor service areas (DSAs). We examined adult recipients of primary, non-status 1 liver-only transplants from 2003 to 2009. The likelihood of undergoing LDLT was compared to the likelihood of undergoing DDLT by multivariate logistic regression. We examined the adjusted odds ratio (OR) for undergoing LDLT versus DDLT for patients with the same diagnosis and blood type after we stratified the DSAs into quintiles by the median match Model for End-Stage Liver Disease (MELD) scores. LDLT was performed for 1497 of 32,927 liver transplants (4.5%). LDLT decreased in frequency by approximately 30% from 2003 to 2009. In comparison with DDLT recipients, LDLT recipients were younger and had higher albumin levels, lower body mass indices, and lower match MELD scores. Females had increased odds of LDLT in comparison with males (OR = 1.74, P < 0.001). Patients with MELD exception scores were less likely to undergo LDLT (OR = 0.22, P < 0.001). Patients with cholestatic liver disease (adjusted OR = 2.04, P < 0.001) or malignant neoplasms other than hepatocellular carcinoma (adjusted OR = 3.33, P < 0.001) were more likely than patients with hepatitis C virus to undergo LDLT. Other characteristics associated with decreased odds of LDLT were black race (adjusted OR = 0.41, P < 0.001) and government insurance (adjusted OR = 0.51, P < 0.001). LDLT was more frequent in DSAs with high median MELD scores; the adjusted OR for LDLT was 38 for the DSAs in the highest quintile (P < 0.001). In conclusion, there are significant differences associated with race, insurance, sex, MELD exceptions, and DSA MELD scores between patients who undergo LDLT and patients who undergo DDLT. These differences can be hypothesized to be driven in part by the relative availability of LDLT versus DDLT at both the patient level and the DSA level.     

Unilateral ischemic preconditioning and heterologous preconditioning in living donor liver transplantation

Testa G, Angelova V, Laricchia‐Robbio L, Rondelli D, Chejfec G, Anthony T, Benedetti E. Unilateral ischemic preconditioning and heterologous preconditioning in living donor liver transplantation.
Clin Transplant 2010: 24: 334–340. © 2009 John Wiley & Sons A/S. Abstract: Ischemic preconditioning (IP) exerts a protective effect on tissues undergoing prolonged ischemia. No studies have been performed to assess the clinical impact of IP on normal human liver used for living donor transplantation (LDLT). Heterologous preconditioning (HP) protects liver tissue as demonstrated in a rat model. Our study investigates the impact that IP and HP have on the donor and recipient liver in LDLT. Twenty candidates for living donor right hepatectomy were divided in two groups. The study group underwent 10′ unilateral ischemia by clamping the right portal vein and hepatic artery at the end of the parenchymal transection. Demographics, laboratory values, biopsy studies, IL‐1Ra, Ki‐67, and CytoDEATH stains were compared. The results show that 10′ ischemia does not exert significant clinical and laboratory changes in living donor hepatectomy candidates.     

Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during transplantation: A prospective, randomized clinical trial.

OBJECTIVE: To assess the safety and efficacy of myocardial protection of the donor heart during transplantation with the use of blood cardioplegia, a prospective randomized clinical trial was undertaken between January 1997 and March 1998. METHODS: Forty-seven consecutive patients were assigned either to crystalloid (27 patients; group 1) or blood cardioplegia (20 patients; group 2). Comparison of recipient age (54 +/- 11 years vs 55 +/- 7 years; P =. 9), sex (89% vs 90% male patients; P =.9), diagnosis (63% vs 65% dilated cardiomyopathy; P =.8), elevated pulmonary vascular resistance (30% vs 30%; P =.9), prior cardiac operations (22% vs 30%; P =.5), need for urgent heart transplantation (7% vs 20%; P =. 2), donor age (32 +/- 11 years vs 31 +/- 13 years; P =.7), cause of death (33% vs 40% vascular; P =.5), and global myocardial ischemia (176 +/- 51 minutes vs 180 +/- 58 minutes; P =.5) showed no difference. Hemodynamically unstable donors (15% vs 45%; P =.02) were more prevalent in group 2. RESULTS: Operative mortality rates (4% vs 5%; P =.8), high-dose inotropic support (41% vs 30%; P = 0.6), and postoperative mechanical assistance (11% vs 10%; P = 0.9) were comparable in the 2 groups. Prevalence of acute right heart failure (27% vs 0; P =.02) and of temporary complete atrioventricular block (52% vs 20%; P =.02) were greater in group 1. Spontaneous sinus rhythm recovery was more prevalent in group 2 (11% vs 40%; P =.02). Higher peak creatine kinase (1429 +/- 725 u/L vs 868 +/- 466 u/L; P =.01) and creatine kinase MB (144 +/- 90 u/L vs 102 +/- 59 u/L; P =. 06) levels suggested more severe ischemic injury in group I. CONCLUSION: Use of blood cardioplegia was associated with a lower prevalence of right heart failure, cardiac rhythm dysfunction, and laboratory evidence of ischemia.     

Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation.

In this retrospective study of hepatitis C virus (HCV)-infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.     

Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis.

Expanded criteria donor (ECD) liver grafts have a higher likelihood of primary graft failure (PGF) compared with standard criteria donor (SCD) grafts. Given a choice between an available ECD graft versus waiting for an SCD graft that may not always become available, what should liver transplant candidates do? The study's aim was to estimate 1-year survival comparing immediate ECD liver grafting with waiting for an SCD organ. Using UNOS data, published literature estimates, and expert opinion, we constructed a Markov decision analytic model to estimate survival while waiting for an SCD transplant and survival with immediate ECD transplant. Sensitivity analyses were performed by varying model parameters individually and simultaneously with a second-order Monte Carlo simulation. For all patients with MELD scores >20, survival was higher with immediate ECD transplant despite the additional increased risk for PGF. Survival was better with an immediate ECD transplant unless the probability of PGF exceeded 23%, 72%, and 88% for recipients with MELD scores of 11-20, 21-25, and 26-30 respectively. For patients with MELD scores >30, the survival benefit with the immediate ECD strategy persisted at even higher rates of PGF. In conclusion, our results suggest that, despite the higher risk for PGF, transplantation with an available ECD graft should be preferred over waiting for an SCD organ for patients with advanced MELD scores. At less advanced MELD scores, the survival benefit depends on the risk of PGF associated with the ECD organ.     

Anesthetic management in pediatric liver transplantation: a comparison of deceased or live donor liver transplantations

Purpose  

Pediatric liver transplantations (LT) are becoming increasingly more common in the treatment of a child with end-stage liver disease. The aim of this study was to evaluate the perioperative anesthetic experience of pediatric patients undergoing deceased and live donor liver transplantations.     

Clinical trial on the cost-effectiveness of T-tube use in an established deceased donor liver transplantation program

The aim of our study was to assess the advantages and disadvantages of T-tube use in liver transplantation, with also paying attention to the economic costs derived from its use. Patients were prospectively randomized to T tube or no T tube. One hundred and seven patients, 53 with T tube and 54 without T tube, were analyzed. Minimum follow-up was three months. Nine patients (8.4%) had bile leak: six in the T-tube group (11.3%) and three in the group without T tube (5.5%), p = ns. Four patients (3.5%) had anastomotic biliary stenosis: one in the T-tube group (1.8%) and three in the group without T tube, p = ns. Twenty of the 53 patients (37.7%) with T tube had T-tube-related complication. The number of diagnostic and therapeutic resources were higher in the T-tube group compared with non-T tube (81 and 17 vs. 18 and 10, respectively, p <0.05). The costs of therapeutic procedures required for the treatment of complications were 28 232 euro in the T-tube group vs. 16 088 euro in the no T-tube group, p <0.05. In conclusion, the systematic use of the T tube in biliary reconstruction in liver transplantation cannot be justified.     

Living donor liver transplantation for hepatitis C-related cirrhosis: no difference in histological recurrence when compared to deceased donor liver transplantation recipients.

The question of possible earlier and more aggressive recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT) remains unanswered. To address this issue we retrospectively reviewed virological, histological, and clinical data in 67 patients (52 DDLT and 15 LDLT) who underwent liver transplant for their HCV-related cirrhosis since April 2001. Our data indicate that there is no statistical difference between LDLT and DDLT groups in mean age, Child-Turcotte-Pugh score, model for end-stage liver disease score, and gender distribution. The mean follow-up was 749 +/- 371 days in LDLT and 692 +/- 347 days in DDLT. The predominant genotype in the LDLT and DDLT are genotype 1 (LDLT, 91%; DDLT, 70%). All patients with histologically confirmed recurrent HCV had detectable HCV-RNA in serum. The histological recurrence rate of hepatitis C was 58% at 4 months, 90% at 1 year, and 100% at 2 years in LDLT patients vs. 71% at 4 months, 94% at 1 year, and 95% at 2 years in DDLT patients (not significant) Comparison of the activity of inflammation and fibrosis score at all time points failed to show a statistical difference. Kaplan-Meier survival analysis showed similar patient and graft survival rates between the 2 groups. Our data indicate that histological recurrence of HCV is an early event and virtually universal 2 years' posttransplantation, regardless of modality of donor procurement.     

Ischemic preconditioning versus intermittent vascular occlusion in liver resections performed under selective vascular exclusion: a prospective randomized study

BACKGROUND: The aim of this study was to compare ischemic preconditioning with the intermittent vascular occlusion technique in liver resections performed under inflow and outflow occlusion. METHODS: Fifty-four patients with resectable liver tumors assigned were randomly to undergo surgery with either ischemic preconditioning (IP group, n = 27) or with intermittent vascular occlusion (IVO group, n = 27). Both groups were compared regarding surgical parameters, aspartate transaminase levels, and apoptosis. RESULTS: For warm ischemic time less than 40 minutes, no significant difference was noticed between the 2 groups apart from caspase-3 activity, which was higher in the IVO group than in the IP group (17.2 +/- 3.4 vs. 10.3 +/- 5.2, P < .05). When warm ischemia exceeded 40 minutes, the IP group showed higher levels in blood aspartate transaminase levels on day 3 (442 +/- 178 IU/L vs. 305 +/- 104 IU/L, P < .05) and higher caspase-3 levels (26.5 +/- 5.7 count/high-power field [hpf] vs. 20.7 +/- 3.6 count/hpf, P < .05) and apoptotic activity (28.5 +/- 7.5 count/hpf vs. 20.2 +/- 4.1 count/hpf, P < .05), as compared with the IVO group. CONCLUSIONS: Although both techniques showed comparable efficacy for short ischemic times, intermittent vascular occlusion provided better cytoprotection when ischemia exceeded 40 minutes.     

Ischemic preconditioning of cadaver donor livers protects allografts following transplantation

BACKGROUND: Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts. METHODS: Cadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets. RESULTS: IP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation. CONCLUSION: IP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.