Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient-years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO-identical and 23 (6.1%) ABO-compatible. The 5-year cumulative incidence of death was 11.2% (SE 1.4%), and of transplantation 72.5% (SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation.

The price of donation after cardiac death in liver transplantation: a prospective cost-effectiveness study.

This study aims to perform a detailed prospective observational multicenter cost-effectiveness study by comparing liver transplantations with donation after brain death (DBD) and donation after cardiac death (DCD) grafts. All liver transplantations in the three Dutch liver transplant centers between 2004 and 2009 were included with 1-year follow-up. Primary outcome parameter was cost per life year after transplantation. Secondary outcome parameters were 1-year patient and graft survival, complications, and patient-level costs. From 382 recipients that underwent 423 liver transplantations, 293 were primarily transplanted with DBD and 89 with DCD organs. Baseline characteristics were not different between both groups. The Donor Risk Index was significantly different as were cold and warm ischemic time. Ward stay was significantly longer in DCD transplantations. Patient and graft survival were not significantly different. Patients receiving DCD organs had more and more severe complications. The cost per life year for DBD was € 88,913 compared to € 112,376 for DCD. This difference was statistically significant. DCD livers have more and more severe complications, more reinterventions and consequently higher costs than DBD livers. However, patient and graft survival was not different in this study. Reimbursement should be differentiated to better accommodate DCD transplantations.

Honoring the contract with our patients: outcome after repeated re-transplantation of the liver.

The aim of this study was to describe the outcome after repeated orthotopic liver re-transplantations (re-OLT) in a population of adults and children, and to determine whether such repeated re-transplantations are an effective treatment or should be considered futile. In a consecutive series of 867 patients, 628 adults and 239 children, who underwent OLT at the University Medical Center Groningen, 23 patients (2.7%), 10 adults and 13 children, underwent more than two re-transplantations of the liver between March 1979 and October 2008. All 23 patients had a second re-transplantation, and seven of them received a third transplant. The overall actuarial patient survival at 1, 5, and 10 yr after primary OLT was 96%, 87%, and 71%, respectively. The overall actuarial patient survival after the second re-OLT was 78%, 73%, and 67%, respectively. Sixteen patients (70%) survived long term. However, for the 23 repeated re-transplantation patients, 76 grafts were used. In a simulation calculation, it was shown that honoring the initial commitment to the 23 patients ultimately led to more surviving patients and less death than if treatment of the original patients was stopped after the first re-transplantation and the remaining grafts were allocated to other primary graft recipients.

[Liver donors no longer foot the bill Compensation for medical costs and loss of income]. / Leverdonor niet langer kind van de rekening. Tegemoetkoming voor medische kosten en gederfde inkomsten.

Organ donation is at the centre of medical and societal attention. An important reason for this is the shortage of donors and thus organs. One of these shortages concerns cadaveric-donor livers. The alternative is living-donor liver transplantation. Until recently, the donors' healthcare costs and loss of income were impediments to living-donor liver transplantation. However, the Dutch government has now removed these obstacles, on the one hand by covering the medical costs associated with the donation, the travelling costs of the donor and a companion, and on the other hand by a subsidy to cover loss of income for the self-employed. This subsidy is limited to a maximum and does not include full compensation for salaried workers fully disabled for work as a result of medical complications of the donation. Complication insurance is needed similar to that developed for kidney donors.

The clinical relevance of the anhepatic phase during liver transplantation.

This study assesses the relation between the anhepatic phase duration and the outcome after liver transplantation. Of 645 patients who underwent transplantation between 1994 and 2006, 194 were recipients of consecutive adult primary piggyback liver transplants using heart-beating donors. The anhepatic phase was defined as the time from the physical removal of the liver from the recipient to recirculation of the graft. Other noted study variables were the cold and warm ischemia times, donor and recipient age, donor and recipient body mass index, perioperative red blood cell (RBC) transfusion, indication for transplantation, and Model for End-Stage Liver Disease score. The primary outcome parameter was graft dysfunction, which was defined as either primary nonfunction or initial poor function according to the Ploeg-Maring criteria. The median anhepatic phase was 71 minutes (37-321 minutes). Graft dysfunction occurred in 27 patients (14%). Logistic regression analysis showed an anhepatic phase over 100 minutes [odds ratio (OR), 4.28], a recipient body mass index over 25 kg/m(2) (OR, 3.21), and perioperative RBC transfusion (OR, 3.04) to be independently significant predictive factors for graft dysfunction. One-year patient survival in patients with graft dysfunction was 67% versus 92% in patients without graft dysfunction (P < 0.001). A direct relation between the anhepatic phase duration and patient survival could, however, not be established. In conclusion, this study shows that liver transplant patients with an anhepatic phase over 100 minutes have a higher incidence of graft dysfunction. Patients with graft dysfunction have significantly worse 1-year patient survival.

The evolution of surgical techniques in clinical liver transplantation. A review.

Currently, liver transplantation (LT) is an accepted method of treatment of end-stage liver disease, metabolic diseases with their primary defect in the liver and unresectable primary liver tumors. Surgical techniques in LT have evolved considerably over the past 40 yr. The developments have led to a safer procedure for the recipient reflected by continuously improving survival figures after LT. Also the new techniques offer the possibility of tailoring the operation to the needs and condition of the recipient as in partial grafting or in different revascularization techniques, or in techniques of biliary reconstructions. In addition, the new techniques such as split LT, domino transplantation and living donor LT have brought about an increase in the available grafts. In this review the evolution of surgical techniques in LT over the past 40 yr and their contribution to the current results are discussed.

Cost of liver transplantation: a systematic review and meta-analysis comparing the United States with other OECD countries.

Large cost variations of liver transplantation are reported. The aim of this study was to assess cost differences of liver transplantation and clinical follow-up between the United States and other Organization for Economic Cooperation and Development (OECD) countries. Eight electronic databases were searched, and 2,000 citations published after 1990 with more than 10 transplantations, and with original cost data, were identified. A total of 30 articles included 5,975 liver transplantations. Meta-analysis was used to derive a combined mean using a random-effects model to test for heterogeneity between studies. Estimated mean cost of a U.S. liver transplantation was US$163,438 (US$145,277-181,598) compared to US$103,548 (US$85,514-121,582) for other OECD countries. Patient characteristics, disease characteristics, quality of the health care provider, and methodology could not explain this cost difference. Health system characteristics differed between the U.S. and other OECD countries. Cost differences in liver transplantation between these two groups may be largely explained by health system characteristics.

Liver transplantation in patients with hepatocellular carcinoma.

Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the Milan criteria survival decreases. Staging of patients with HCC in a cirrhotic liver is deficient due to the restrictions of the current imaging modalities. The exact place of tumor controlling therapies during the waiting time for transplantation is not yet clear. No evidence of sufficient level is available as to the efficacy of pre-, per- or postoperative chemotherapy. Promising new drugs are currently tested. This counts also for the use of new immunosuppressant with concomitant tumor suppressive capabilities.

The survival paradox of elderly patients after major liver resections.

OBJECTIVE: The objective of this study is to assess the outcome of liver resections in the elderly in a matched control analysis. PATIENTS AND METHODS: From a prospective single center database of 628 patients, 132 patients were aged 60 years or over and underwent a primary major liver resection. Of these patients, 93 could be matched one-to-one with a control patient, aged less than 60 years, with the same diagnosis and the same type of liver resection. The mean age difference was 16.7 years. RESULTS: Patients over 60 years of age had a significantly higher American Society of Anaesthesiologists (ASA) grade. All other demographics and operative characteristics were not different. In-hospital mortality and morbidity were higher in the patients over 60 years of age (11% versus 2%, p = 0.017 and 47% versus 31%, p = 0.024). One-, 3-, and 5-year survival rates in the patients over 60 years of age were 81%, 58%, and 42%, respectively, compared to 90%, 59%, and 42% in the control patients (p = 0.558). Unified model Cox regression analysis showed that resection margin status (hazard ratio 2.51) and ASA grade (hazard ratio 2.26), and not age, were determining factors for survival. CONCLUSION: This finding underlines the important fact that in patient selection for major liver resections, ASA grade is more important than patient age.

Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization.

OBJECTIVE: To study the impact of perineural growth as a prognostic factor in periampullary adenocarcinoma (pancreatic head, ampulla of Vater, distal bile duct, and duodenal carcinoma). SUMMARY BACKGROUND DATA: Pancreatic head carcinoma is considered to have the worst prognosis of the periampullary carcinomas. Several other prognostic factors for periampullary tumors have been identified, eg, lymph node status, free resection margins, tumor size and differentiation, and vascular invasion. The impact of perineural growth as a prognostic factor in relation to the site of origin of periampullary carcinomas is unknown. METHODS: Data of 205 patients with periampullary carcinomas were retrieved from our prospective database. Pancreaticoduodenectomy was performed in 121 patients. Their clinicopathological data were reviewed and analyzed in a multivariate analysis. RESULTS: Perineural growth was present in 49% of the cases (37 of the 51 patients with pancreatic head carcinoma; 7 of the 30 patients with ampulla of Vater carcinoma; 7 of the 19 with distal bile duct carcinoma; and 8 of the 21 with duodenal carcinoma). Overall 5-year survival was 32.6% with a median survival of 20.7 months. Median survival in tumors with perineural growth was 13.1 months compared with 36.0 months in tumors without perineural growth (P < 0.0001) Using multivariate analysis, the following unfavorable prognostic factors were identified: perineural growth (RR = 2.90, 95% CI 1.62-5.22), nonradical resection (RR = 2.28, 95% CI 1.19-4.36), positive lymph nodes (RR = 1.96, 95% CI 1.11-3.45), and angioinvasion (RR = 1.79, 95% CI 1.05-3.06). Portal or superior mesenteric vein reconstruction and tumor localization were not of statistical significance. CONCLUSION: Perineural growth is a more important risk factor for survival than the primary site of periampullary carcinomas.

The outcome of primary liver transplantation from deceased donors in children with body weight < or =10 kg.

Between November 1982 and March 2006, 67 children with body weight < or =10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0-7.0), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight < or =10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.

The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation.

BACKGROUND: Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after orthotopic liver transplantation (OLT). Although experimental studies have shown that platelets contribute to reperfusion injury of the liver, the influence of allogeneic platelet transfusion on outcome has not been studied in detail. In this study, we evaluate the impact of various blood products on outcome after OLT. METHODS: Twenty-nine variables, including blood product transfusions, were studied in relation to outcome in 433 adult patients undergoing a first OLT between 1989 and 2004. Data were analyzed using uni- and multivariate stepwise Cox's proportional hazards analyses, as well as propensity score-adjusted analyses for platelet transfusion to control for selection bias in the use of blood products. RESULTS: The proportion of patients receiving transfusion of any blood component decreased from 100% in the period 1989-1996 to 74% in the period 1997-2004. In uni- and multivariate analyses, the indication for transplantation, transfusion of platelets and RBC were highly dominant in predicting 1-yr patient survival. These risk factors were independent from well-accepted indices of disease, such as the Model for End-Stage Liver Disease score and Karnofsky score. The effect on 1-yr survival was dose-related with a hazard ratio of 1.377 per unit of platelets (P = 0.01) and 1.057 per unit of RBC (P = 0.001). The negative impact of platelet transfusion on survival was confirmed by propensity-adjusted analysis. CONCLUSION: This retrospective study indicates that, in addition to RBC, platelet transfusions are an independent risk factor for survival after OLT. These findings have important implications for transfusion practice in liver transplant recipients.

Vascular events after liver transplantation: a long-term follow-up study.

Long-term follow-up studies on the impact of vascular events (VE) and risk factors of liver transplant recipients are scarce. In this study, 311 recipients of a first isolated liver transplant who survived at least 1 year were followed up from 1979 to 2002. The median follow-up duration was 6.2 (range1-22.7) years. Overall median survival was 18.7 [95% confidence interval (CI): 15.5-20.1] years and this was significantly lower compared with age- and sex-matched controls. Eleven (21%) of the patients had a vascular cause of death and VE were the third cause of death. VE occurred later compared with other causes of death (mean 10.3 years vs. 4.5 years, P < 0.0001, 95% CI: 2.7-8.9). Systolic hypertension, systolic blood pressure, smoking, renal failure, age, hypertriglyceridemia, serum total cholesterol levels and hypercholesterolemia at the 1-year follow-up visit were associated with the occurrence of VE, but renal failure and age at 1 year after transplantation were the only independent risk factors for vascular death (hazard ratio 0.06, 95% CI: 0.01-0.41 and hazard ratio 1.17, 95% CI: 1.02-1.34, respectively). Finally, it was shown that the adequate treatment of hypertension was associated with a significant reduced risk of vascular death. Therefore, vascular risk factors should be treated aggressively to prevent VE in the long term.

Nonanastomotic biliary strictures after liver transplantation, part 1: Radiological features and risk factors for early vs. late presentation.

Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). The exact pathogenesis is unclear. Purpose of this study was to identify risk factors for the development of NAS after OLT. A total of 487 adult liver transplants with a median follow-up of 7.9 years were studied. All imaging studies of the biliary tree were reviewed. Cholangiography was routinely performed between postoperative days 10-14 and later on demand. Localization of NAS at first presentation was categorized into 4 anatomical zones of the biliary tree. Severity of NAS was semiquantified as mild, moderate, or severe. Donor, recipient, and surgical characteristics and variables were analyzed to identify risk factors for NAS. NAS developed in 81 livers (16.6%). Thirty-seven (7.3%) were graded as moderate to severe. In 85% of the cases, anatomical localization of NAS was around or below the bifurcation of the common bile duct. A large variation was observed in the time interval between OLT and first presentation of NAS (median 4.1 months; range 0.3-155 months). NAS presenting early (< or =1 year) after OLT were associated with preservation-related risk factors. Cold and warm ischemia times were significantly longer in patients with early NAS compared with NAS presenting late (>1 year) after OLT (694 minutes vs. 490 minutes, P = 0.01, and 57 minutes vs. 53 minutes, P < 0.05, respectively), and early NAS were more frequently located in the central bile ducts. NAS presenting late (>1 year) after OLT were found more frequently in the periphery of the liver and were more frequently associated with immunological factors, such as primary sclerosing cholangitis, as the indication for OLT (24% vs. 45%, P < 0.05). By separating cases of NAS on the basis of the time of presentation after transplantation, we were able to identify differences in risk factors, indicating different pathogenic mechanisms depending on the time of initial presentation.

Nonanastomotic biliary strictures after liver transplantation, part 2: Management, outcome, and risk factors for disease progression.

Nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) are associated with high retransplant rates. The aim of the present study was to describe the treatment of and identify risk factors for radiological progression of bile duct abnormalities, recurrent cholangitis, biliary cirrhosis, and retransplantation in patients with NAS. We retrospectively studied 81 cases of NAS. Strictures were classified according to severity and location. Management of strictures was recorded. Possible prognostic factors for bacterial cholangitis, radiological progression of strictures, development of severe fibrosis/cirrhosis, graft survival, and patient survival were evaluated. Median follow-up after OLT was 7.9 years. NAS were most prevalent in the extrahepatic bile duct. Twenty-eight patients (35%) underwent some kind of interventional treatment, leading to a marked improvement in biochemistry. Progression of disease was noted in 68% of cases with radiological follow-up. Radiological progression was more prevalent in patients with early NAS and one or more episodes of bacterial cholangitis. Recurrent bacterial cholangitis (>3 episodes) was more prevalent in patients with a hepaticojejunostomy. Severe fibrosis or cirrhosis developed in 23 cases, especially in cases with biliary abnormalities in the periphery of the liver. Graft survival, but not patient survival, was influenced by the presence of NAS. Thirteen patients (16%) were retransplanted for NAS. In conclusion, especially patients with a hepaticojejunostomy, those with an early diagnosis of NAS, and those with NAS presenting at the level of the peripheral branches of the biliary tree, are at risk for progressive disease with severe outcome.

Outcome and pattern of recurrence after curative resection for hepatocellular carcinoma in patients with a normal liver compared to patients with a diseased liver.

BACKGROUND/AIMS: The purpose of this study was to investigate whether differences existed in demography and outcome after resection for hepatocellular carcinoma (HCC) in patients with a normal liver compared to patients with a diseased liver. METHODOLOGY: Twenty-seven Caucasian patients with HCC in a histologically proven normal liver (NL group) in the Netherlands and 141 Asian patients with HCC in a diseased liver (DL group) in Japan underwent a curative liver resection. Patient and tumor characteristics, post-resectional disease-free, overall survival rates and pattern of recurrence were investigated. RESULTS: HCC's in the NL group were found to be larger, in a more advanced stage and needed more extended resections compared to HCC's in the DL group. Microvascular invasion was similar in both groups, while capsule formation was observed less in the NL group. Overall survival and disease-free survival after curative resection were not statistically different between both groups. Also even after stratification for T-stage, there was no difference in survival. Although the rate of recurrence was similar in both groups, a significantly higher number of extrahepatic metastases was observed in the NL group. CONCLUSIONS: Distinct demographic differences existed between patients with HCC in the NL group compared to patients in the DL group. Extrahepatic recurrences were more frequent after curative resection for HCC in a normal liver. No difference in survival was demonstrated between both groups.

End-to-side caval anastomosis in adult piggyback liver transplantation.

No consensus exists regarding the optimal reconstruction of the cavo-caval anastomosis in piggyback orthotopic liver transplantation (PB-LT). The aim of this study was to analyze our experience with end-to-side (ES) cavo-cavostomy. Outcome parameters were patient and graft survival and surgical complications. During the period 1995-2002 146 full-size PB-LT in 137 adult patients were performed with ES cavo-cavostomy without the routine use of temporary portocaval shunt (TPCS). In 12 patients (8%) this technique was used for implantation of second or third grafts. Veno-venous bypass was not used in any case and TPCS was performed only in eight patients (6%). One-, three- and five-yr patient and graft survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median number of intraoperative transfusion of packed red blood cells (RBC) was 2.0 (range 0-33) and 30% of the patients (n = 43) did not require any RBC transfusion. Surgical complications of various types were observed after 49 LT (34%) and none of the complications was specifically related to the technique of ES cavo-cavostomy. Our experience indicates that PB-LT with ES cavo-cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations.

Dynamics of the vascular profile of the finer branches of the biliary tree in normal and diseased human livers.

BACKGROUND/AIMS: Results of our previous studies supported the concept that in the human liver, the smallest ramification of the biliary tree, the bile ductules, might contain hepatic progenitor cells. An insufficient proliferative response and loss of bile ductules preceded bile duct loss whereas preservation of bile ductules mitigated bile duct loss. METHODS: Presently we investigated the vascular profile of the bile ductules in diseased human livers and livers showing normal histological features as controls, using CD34, CK7 and alphaSMA antibodies in a double immunolabeling technique. VEGF-A expression was also studied. In control livers bile ductules traversed the boundaries of the portal tract into the lobule as ductular-vascular units, in a pattern outlining the classic hexagonal lobule, following the vascular septa. The latter are thought to be extensions of portal veins. In diseased states the two structures reacted in unison. Increased or decreased numbers of ductules were consistently accompanied by similar changes of accompanying microvessels. Increased numbers of ductules and microvessels were paralleled by increased ductular expression of VEGF-A. RESULTS: Our data support the concept that the smallest branches of the biliary tree might have their own vascular supply and that the ductules might in turn maintain their vasculature during regenerative processes.

Surgical injuries of postmortem donor livers: incidence and impact on outcome after adult liver transplantation.

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one-third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT.