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Background: The outcomes of liver resection (LR) with a narrow margin in patients with transplantable hepatocellular carcinoma (HCC) have not been studied. The aim was to assess whether narrow margin following up-front LR impacts the incidence, timing, pattern, and transplantability of tumor recurrence in patients with initially transplantable HCC., Methods: All initially transplantable HCC patients undergoing hepatectomy with either narrow (<10 mm) or wide (≥10 mm) margins from 2007 to 2016 at four Western university centers were compared in terms of recurrence, transplantability of recurrence, recurrence-free survival (RFS), and intention-to-treat overall survival (ITT-OS). Independent predictors of non-transplantability of recurrence were assessed., Results: This study included 187 patients (narrow group, n = 107 vs. wide group, n = 80). Recurrence was significantly more frequent in the narrow margin group (44% vs. 26%; p = 0.01) with a shorter RFS (p = 0.03). The transplantability of recurrence and ITT-OS were, however, not different between the two groups. The presence of satellite nodules on the resected specimens emerged as the sole independent predictor of non-transplantability of tumor recurrence. The stratification of the analysis according to the presence of cirrhosis achieved essentially the same results as in the whole study population., Conclusions: Narrow margin was associated with a higher tumor recurrence rate and a shorter RFS for patients with initially transplantable HCC. However, transplantability of recurrence and long-term ITT-OS were not impaired.

Background: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation., Methods: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2 ) were also utilized., Results: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery., Conclusion: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Steroid-resistant acute rejection (SR-AR) and ductopenic rejection (DR) after liver transplantation are infrequent, but difficult to manage. We performed a retrospective review of patients with SR-AR or DR treated with sirolimus-based therapy. Since 2002, we have treated five patients with SR-AR and eight patients with DR. All patients had associated renal insufficiency. Six patients showed no response, of whom five died and one was retransplanted. In six cases, rejection was resolved after changing, while one improved. Therefore, the total response rate was 54%. Ten of 13 patients (77%) suffered some type of adverse event. Ten of these (77%) suffered a hematologic event. Four patients (31%) had infection. Only two patients had to discontinue treatment. Univariate analysis showed that pre-conversion bilirubin was lower in responders (Bilirubin: R: 210 +/- 205 vs. NoR: 554 +/- 159 micromol/L; p = 0.07 and Creatinine clearance higher: R: 37 +/- 11 vs. NoR: 25 +/- 11 mL/min; p = 0.09). Sirolimus trough levels one month after switching were higher in responders (R: 11 +/- 1.8 vs. NoR: 7.5 +/- 3.3 ng/mL; p = 0.03). We conclude that a dual therapy regimen of tacrolimus and sirolimus can achieve a high response rate as a rescue therapy for SR-AR and DR, provided it is begun as soon as possible.

The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV-recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short-term evolution of HCV recurrence.

Background: Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution., Aim: The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution., Patients and Methods: Between 1999 and 2004, 366 liver transplants were performed in 335 patients. Forty-two patients [12.5%: portal vein thrombosis (PVT) group] had portal thrombosis at the time of LT. We analyzed the technical aspects and compared their evolution with a group of patients without portal thrombosis (n = 293; no-PVT group). Retransplantations were excluded., Results: Of the 42 patients with thrombosis, 18 had partial thrombosis and 16 complete thrombosis [six included the proximal superior mesenteric vein (SMV) and in two the whole splanchnic system]. In 12 cases, usual T-T anastomosis was performed and in 16 cases a thrombectomy was carried out; there were five cases of anastomosis at confluence of the SMV, five cases of anastomosis to a collateral vein, three cases of venous graft, and one case of cavoportal hemitransposition. The operative time was higher in PVT group (417 +/- 103 min vs. 363 +/- 83; p = 0.0005), as RBC transfusion (2.4 +/- 3.1 vs. 1.9 +/- 2.3; p = 0.04), and hospital stay (20.9 +/- 14.9 d vs. 15.1 +/- 10.6; p = 0.002). However, there were no differences in hospital mortality (4% vs. 7.8%; p = 0.98), primary dysfunction (4.8% vs. 7.8%; p = 0.44), or three-yr-actuarial survival (75% vs. 77%; p = 0.95). The incidence of post-transplant thrombosis was higher in the PVT group (15% vs. 2.4%; p = 0.0005)., Conclusions: Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality.

Background: Cold ischemia time and the presence of postoperative hepatic arterial thrombosis have been associated with biliary complications (BC) after liver transplantation. An ABO-incompatible blood group has also been suggested as a factor for predisposal towards BC. However, the influence of Rh nonidentity has not been studied previously., Materials: Three hundred fifty six liver transplants were performed from 1995 to 2000 at our hospital. BC incidence and risk factors were studied in 345 patients., Results: Seventy patients (20%) presented BC after liver transplantation. Bile leakage (24/45%) and stenotic anastomosis (21/30%) were the most frequent complications. Presence of BC in Rh-nonidentical graft-host cases (23/76, 30%) was higher than in Rh-identical grafts (47/269, 17%) (P=0.01). BC was also more frequent in grafts with arterial thrombosis (9/25, 36% vs 60/319, 19%; P=0.03) and grafts with cold ischemia time longer than 430 min (26/174, 15% vs 44/171, 26%; P=0.01). Multivariate logistic regression confirmed that Rh graft-host nonidentical blood groups [RR=2(1.1-3.6); P=0.02], arterial thrombosis [RR=2.6(1.1-6.4); P=0.02] and cold ischemia time longer than 430 min [RR=1.8(1-3.2); P=0.02] were risk factors for presenting BC., Conclusion: Liver transplantation using Rh graft-host nonidentical blood groups leads to a greater incidence of BC.

We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric-end-tidal carbon dioxide partial pressure (PCO(2)) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 +/- 7 mm of Hg vs. 17 +/- 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 +/- 15 mm of Hg vs. 79 +/- 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values., ((c) 2006 AASLD)

Background: The outcome of surgical treatment of hepatocellular carcinoma (HCC) could be improved by applying patient selection criteria based on tumoral aggressiveness. Here we analyzed the prognostic role of the expression of several genes involved in cell-cycle regulation in a group of patients with HCC., Methods: We retrospectively studied 93 patients (67 transplanted and 26 resections) treated between 1996 and 2000. In micro-thick sections from paraffin-embedded tumoral tissues, the expression of p53, pRb, p16, and cyclin D1 was analyzed. A logistic regression model was used to detect factors related to vascular invasion. A Cox regression model was applied to identify pathologic and molecular factors with the capacity to predict the recurrence of HCC., Results: Only tumor size>3 cm (odds ratio [OR]: 3.4; 95% CI: 1.2-9.9; P=0.019) and pRb expression (OR: 4.1; 95% CI: 1.02-17; P=0.053) were associated with an increased risk of vascular invasion. The regression model applied to the group of transplanted patients showed three factors that were independently related to recurrence: vascular invasion (OR 7.5; 95% CI: 1.1-51.8; P=0.039); pRb expression (OR: 11; 95% CI: 1.2-96.9; P=0.03); and p16 expression (OR: 69.7; 95% CI: 5.1-9448; P=0.001). In the group of resected patients, pRb expression was associated with higher risk of recurrence only in the univariate analysis (P=0.037). The multivariate analysis showed tumor size>3 cm (OR: 57.5; 95% CI: 1.1-51.8; P=0.039) and vascular invasion (OR: 6.1; 95% CI: 1.05-35.3; P=0.044) to be significantly associated with recurrence., Conclusions: Of the molecular factors studied, only pRb expression was useful as a predictive factor of vascular invasion in patients with HCC, and also of recurrence in transplanted patients with this carcinoma. pRb expression may be relevant to consider when selecting patients for resection and when identifying transplanted patients with a high risk of recurrence.

Steroid-free immunosuppressive regimens reduce corticosteroid-related side effects in liver transplant recipients although their efficacy is very variable. We evaluated the efficacy and safety of a steroid-free regimen in a 6-month, open-label, multicenter, pilot study, which involved 102 liver transplant patients treated with daclizumab (2 mg/kg within 6 h following transplant and 1 mg/kg on day 7), mycophenolate mofetil (MMF, 1 g b.i.d) and tacrolimus (trough levels of 5-15 ng/ml in the first month and 5-10 ng/ml thereafter). One intra-operative dose of methylprednisolone was administered. At 6 months, the acute rejection rate was 9.8%, and patient and graft survival rates were 96% and 95%, respectively. Acute rejection rates were similar for hepatitis C-positive patients (8.6%) and hepatitis C-negative patients (10.4%). Infections occurred in 22% of patients; most cases were considered mild or moderate. Post-transplantation hypertension and diabetes mellitus developed in 37% and 14% of patients, respectively, during the study period, but were markedly less frequent (8% and 6%, respectively) at 6 months. Hypercholesterolemia was observed in only 2% of patients. In conclusion, the steroid-free immunosuppressive regimen of daclizumab, MMF, and tacrolimus effectively prevents acute rejection after liver transplantation without decreasing safety.

Background/aims: The purpose of this study was to evaluate the efficacy of a steroid-free immunosuppression protocol., Methods: From 2001 to 2004, 198 liver-transplant patients were randomized to receive immunosuppression with Basiliximab and cyclosporine, with (St Group) or without (NoSt Group) prednisone. The primary end points were acute rejection, and patient and graft survival. The secondary end points were infection, metabolic complications, and hepatitis C-virus recurrence., Results: Overall rejection rate was 15%, with no differences (St: 13% vs NoSt: 18%; P=0.33). Infection rate was similar in both groups (St: 51% vs NoSt: 47%; P=0.56), but diabetic patients in the St Group had a significantly higher rate of bacterial infections (St: 54% vs NoSt: 14%; P=0.005). The six-month protocol biopsies showed hepatitis C recurrence in 90% of patients, without differences between groups. Hypertension was more frequent in the St Group (St: 44% vs NoSt: 25%; P=0.006). De novo diabetes rate was higher in the St Group (month 1: St: 29% vs NoSt: 18%; P=0.06), with higher glycatedHb (5.1+/-1.1 vs 4.4+/-0.8; P=0.002). Six-month survival rates were similar (St: 89% vs NoSt: 94%, P=0.62)., Conclusions: Immunosuppression without steroids is safe and reduces infection and metabolic complications.

Objective: Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine., Patients and Methods: Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance., Results: A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus-RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation., Conclusions: Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.

Hepatic hydrothorax is a uncommon complication of cirrhotic patients and the results of liver transplantation (OLT) in patients with this complication are not well defined. We studied postoperative complications and survival of 28 patients with hepatic hydrothorax transplanted at our center during a period of 12 years, comparing them with a control group of 56 patients transplanted immediately before and after each case. There were no differences between hydrothorax group and control group in days of mechanical ventilation after surgery, transfusion requirements, postoperative mortality and long-term survival (70% vs. 55% at 8 years, P = 0.11). Long-term evolution was similar between patients with refractory hepatic hydrothorax or spontaneous bacterial empyema and those with noncomplicated hepatic hydrothorax. Hepatic transplantation is an excellent therapeutic option for patients with hepatic hydrothorax. Presence of hepatic hydrothorax does not imply more postoperative complications, and long-term survival is similar to other indications of hepatic cirrhosis.

Objective: We sought to evaluate MR cholangiopancreatography (MRCP) as the only imaging procedure used in the diagnosis and management of biliary complications after orthotopic liver transplantation (OLT)., Conclusion: MRCP is a useful imaging procedure in the assessment of biliary complications after OLT.

Until recently, human immunodeficiency virus (HIV) infection was considered an absolute contraindication for liver transplantation in Spain. We present the first 4 cases of liver transplantation (LT) carried out in our center in patients infected with HIV and coinfected by the hepatitis C virus (HCV), immunosuppressed with cyclosporine A (CyA) and basiliximab, but without steroids. The 4 patients were male, with a mean age of 38.25 +/- 4.5 years. Mean time of HIV infection was 114 +/- 62.3 months and all patients were receiving highly active antiretroviral therapy (HAART). HCV genotypes of the 4 patients were 4, 1b, 1b, and 1a. Two patients were classified as Child-Turcotte-Pugh C (10 and 11 points), 1 was B (8 points), and the patient with hepatocellular carcinoma was A (5 points). Immunosuppression consisted of basiliximab and monotherapy with CyA. There were no postoperative infections. With a follow-up of 17 +/- 8 months, all patients are alive. There was only 1 acute rejection episode, and this was solved with steroid pulses. Three patients showed HCV recurrence with enzymatic and histological changes and were treated with interferon and ribavirin. One patient had negative HCV-ribonucleic acid after 6 months of treatment. In conclusion, HIV infection should not be considered an absolute contraindication for liver transplantation. The evolution of this type of patients will probably depend on the HCV infection. Immunosuppression without steroids may reduce opportunistic infection.

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 +/- 2) and SC group, as compared with the NR group (P <.05, vs SVR) and PT group (P <.05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 +/- 640 pg/ml) in the SC (4474 +/- 300 pg/mL) and SVR groups (3647 +/- 300 pg/mL), but were significantly lower than controls in the PT (401 +/- 331 pg/mL; P <.02) and NR groups (546 +/- 360 pg/mL; P <.01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 +/- 279 pg/mL, 674 +/- 310 pg/mL and 841 +/- 294 pg/mL, respectively), but was lower in PT patients (232 +/- 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome.

The haemophagocytic syndrome is defined as a proliferation of phagocytic macrophages in the bone marrow, lymph nodes and spleen. Clinically, it is characterised by fever and pancytopenia. We present here a case of haemophagocytic syndrome after liver transplantation in a 63-year-old man who had undergone transplantation for autoimmune hepatitis. One month after liver transplantation, he developed ascites, fever and progressive pancytopenia. Bone marrow biopsy showed proliferation of non-neoplastic histiocytes, demonstrating phagocytosis of haemopoietic cells. No infectious or neoplasm-associated disease was found. Several kinds of treatment were attempted, but the course was fatal. The haemophagocytic syndrome is uncommon after liver transplantation, but this diagnosis has to be kept in mind in cases of pancytopenia of unknown origin.

This study analyzes the effect of the preoperative variables of donors and recipients on graft survival after liver transplantation (LT). Preoperative data from a cohort of 122 cirrhotic patients who underwent primary LT were evaluated prospectively. The influence of these variables as risk factors for graft loss was assessed. During follow-up (median: 33 (19-59) months) there were 38 (31.1%) graft losses (22 deaths and 16 retransplantations). Variables that showed statistical association with graft loss on univariate analysis (P<0.150) were: positivity of the CMV serologic status of the donor (P=0.028), the UNOS score of recipient (P=0.048) and advanced donor age (P=0.124). When these variables were introduced into the multivariate study, the CMV serologic status of the donor was the only variable that was independently associated with graft loss (relative risk=2.97, 95% confidence interval=1.05-8.39; P=0.039). Donor CMV-seropositivity is a significant pretransplantation determinant for graft loss in liver transplant recipients.

Objective: To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival., Summary Background Data: Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs., Methods: We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival., Results: The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III-IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma., Conclusions: OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

Objectives of this study are to quantify the need for blood transfusion during liver transplantation (LT) and confirm the importance of intraoperative blood transfusion as an independent prognostic factor for postoperative outcome. Furthermore, we try to detect useful variables for the preoperative identification of patients likely to require transfusion of packed red blood cell units (PRCUs) and identify measures to reduce transfusion needs. Data were collected prospectively between September 1998 and November 2000. One hundred twenty-two LTs were included in the study. Forty-two patients (34%) did not require transfusion of PRCUs. In multivariate analysis, transfusion of more than three PRCUs was found to be the only significant variable associated with prolonged hospital stay. In addition, excluding perioperative deaths, PRCU transfusion, using a cutoff value of six units, was the only variable to reach statistical significance (P =.008; risk ratio, 4.93; 95% confidence interval, 15 to 15.9) to predict survival in a multivariate analysis that also included Child's class and United Network for Organ Sharing (UNOS) classification. Moreover, only preoperative hemoglobin (Hb) level was found to significantly predict the need for transfusion of one or more PCRUs. Finally, only UNOS classification and placement of an intraoperative portacaval shunt were found to be statistically significant to predict the need to transfuse more than six PRCUs. We found the requirement of even a moderate number of blood transfusions is associated with longer hospital stay, and transfusion of more than six PRCUs is associated with diminished survival. Preoperative normalization of Hb levels and placement of an intraoperative portacaval shunt can diminish the number of blood transfusions during LT.

Introduction: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival., Methods: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years., Results: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01)., Conclusion: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.

Aim: Our goal was to retrospectively analyze graft loss and mortality risk factors using multi-centre data on liver retransplantation., Material and Methods: Between 1991-1995, 640 patients underwent 718 liver transplants in Barcelona. Mean age of the 74 patients receiving a second transplant was 47.6 years (range 19-65). Causes of retransplantation were immunologic in 26 patients (35.1%), technical in 23 (31.1%), primary dysfunction in 12 (16.2%), recurrent original disease in 7 (9.5%), and other causes in 6 (8.1%). Mean time between first and second transplant was less than 7 days in 20 patients (27%), between 8 and 30 days in 4 (5.4%) and more than 30 days in 50 patients (67.6%). Recipient, donor, and operative variables were analyzed using univariate (Kaplan-Meier curves) and multivariate techniques (Cox regression) to identify risk factors., Results: Retransplant patient survival at 1 and 5 years was 60.8% and 49.5%, respectively, compared to 75.6% and 64.8% in a series of 640 first transplant patients. Mortality risk factors identified by multivariate analysis were bilirubin >12 mg/dL (RR 2.3; P=.010), recipient age (RR increase 0.04 for each additional year; P=.02), cause for retransplant (immunologic RR 4.01, technical RR 2.7 and other causes RR 6.9; compared to primary dysfunction RR 1; P=.020). Urea >54 mg/dL (0.02) and multiple transfusions >15 units red blood cells (0.001) were only significant in the univariate analysis., Conclusions: In our experience, retransplantation for primary dysfunction is the setting that has the best prognosis. Of the other causes, retransplantation should be performed before the total bilirubin reaches >12 mg/dL or before the appearance of variables indicative of severe renal insufficiency.

Objective: Our aim was to validate Spanish and Catalan versions of the Liver Disease Quality of Life questionnaire (LDQOL) for use in liver transplant patients., Methods: The LDQOL consists of the SF-36 generic measure of health-related quality of life (HRQOL) and 12 disease-specific dimensions for liver disease patients. The Spanish and Catalan versions of the questionnaire were administered to 138 patients with a liver transplant. Cronbach's alpha coefficients (CAC) were used to test the internal consistency of disease-specific scales. Test-retest reliability was calculated using the Intraclass Correlation Coefficient (ICC) in a sub-group of 41 patients who completed the questionnaire on two occasions 1 to 2 weeks apart. Validity was analysed by determining the instrument's capacity to discriminate between patient groups classified according to years since transplant, disease etiology, and symptom severity. Ceiling and floor effects were also calculated., Results: Internal consistency in the disease-specific dimensions was acceptable or good (CACs 0.60-0.97), as was test-retest reliability in all dimensions (statistically significant CCIs of 0.62-0.89), except the symptoms dimension (CCI=0.46, P<.05). Few differences were found in disease-specific dimension scores between patients classified according to number of years since transplant or etiology, but differences were found in some dimensions according to symptom severity. Moderate to severe ceiling effects were found in several disease-specific dimensions., Conclusions: The Spanish and Catalan versions of the LDQOL may be useful for measuring HRQOL in this population, though it will be important to investigate further the instrument's sensitivity to change.

PAF antagonists have been used in xenotransplantation to alleviate the pathogenesis of hyperacute rejection. This study evaluated the ability of the PAF antagonist UR-12670 to improve graft function in late xenograft rejection (LXR) in an orthotopic liver xenotransplantation model, and the involvement of PAF (platelet activating factor) in this type of rejection. The recipients of a hamster xenograft received standard immunosuppression (tacrolimus 0.2 mg/kg/30 days, MMF 25 mg/kg/8 days). Study groups: group A, without UR-12670, group B, UR-12670 (20 mg/kg/8 d) and group C, continuous administration of UR-12670 (20 mg/kg/d). Serum levels of xenoantibodies were evaluated by flow cytometry and tissue deposits by immunofluorescence. Immunoblot and indirect immunofluorescence assessed specificity of xenoantibodies. Conventional histology was performed. Continuous administration of UR-12670 improved the histological pattern of liver xenografts, especially necrosis, loss of hepatocytes, hemorrhage, sinusoidal congestion and lymphocyte infiltration. There was not a shift in specificity of xenoantibodies at different times posttransplantation, as demonstrated by immunoblotting and indirect immunofluorescence. UR-12670 administration had a beneficial effect on graft function and considerably improved the histopathological pattern, but it failed to induce tolerance after withdrawal of immunosuppression. UR-12670 had an immunomodulatory effect on cellular response but not on antibody production. There was not a change in the specificity of xenoantibodies produced at LXR compared with pretransplant antibodies.

The best system for organ allocation is still a controversial issue. The aim of this study was to study the accuracy of four different scores to predict mortality on the waiting list and, thus, their usefulness to determine organ allocation. We retrospectively compared two groups of patients, those who died on waiting list (group D) and those who successfully underwent transplantation (group T) during the same time period. Four scores, at the time of entering the waiting list and just before liver transplantation or death, were evaluated. The evaluated scores were as follows: (1) the Child-Pugh classification; (2) the Model for End-Stage Liver Disease (MELD) score; (3) the Freeman scale; and (4) the Guardiola et al index. The mortality rate on waiting list was 15.9%. All studied scores, except Freeman scale, were higher in group D at the time of entrance on waiting list (MELD, 17.4 +/- 8 v 12.3 +/- 6, P = .02; Child, 9.9 +/- 2 v 7.7 +/- 2, P = .002; Freeman, 9.7 +/- 4 v 7.3 +/- 3.9, P = .09; Guardiola, 2.6 +/- 0.9 v 1.7 +/- 0.7, P = .001). C-statistics of all scores were similar and in all cases lower than 0.8 (MELD, 0.75; Child, 0.78; Freeman, 0.65; Guardiola, 0.79). None of the studied scores have an excellent accuracy to predict prognosis of patients on waiting list, mainly in case of populations with high proportion of hepatocellular carcinoma. Although the MELD score is rapidly available, standardized, and objective, it does not reflect the severity of patients with cancer or metabolic disorders.

Background: In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient., Patients and Method: Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed., Results: Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up., Conclusion: The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.

Aims of this study are to analyze the influence of endothelin-1 (ET-1) on hemodynamic evolution during liver transplantation (LT) and study the role of a temporary portacaval shunt in ET-1 synthesis. Forty LTs in patients with cirrhosis were studied. Two groups were analyzed: the first group had a temporary portacaval shunt during the anhepatic phase, and the second group did not. Portal and systemic ET-1 levels were measured at several times. At the end of the anhepatic phase, systemic (16.1 +/- 6.5 pg/mL) and portal (19.2 +/- 7 pg/mL) ET-1 levels increased, whereas they decreased after reperfusion (systemic, 11.8 +/- 7.1 pg/mL; portal, 13.2 +/- 6.8 pg/mL). Portal flow at the beginning of LT correlated with systemic ET-1 levels (R2 = 0.3; P =.004). A temporary portacaval shunt reduced portal pressure during the anhepatic phase, but did not modify ET-1 levels. Patients with reperfusion syndrome had greater systemic ET-1 levels in the anhepatic phase (19.1 +/- 6.9 v 15.1 +/- 6.1 pg/mL; P =.07). Although there is a relationship between ET-1 levels and portal flow and reperfusion syndrome, no clear clinical effect on hemodynamics could be shown. Creation of a portacaval shunt made no change in ET-1 levels.

Liver transplant recipients are at greater risk for de novo neoplasia, especially lymphoma and nonmelanoma skin cancer; however, risk factors for this complication have not been well studied. Clinical and pathological records of 137 consecutive liver transplant recipients who had survived for at least 1 year were reviewed to register de novo neoplasia. Ten variables were analyzed for their association with the development of de novo malignancies by means of a log-rank test and stepwise selection in a multivariate analysis using the Cox proportional hazard model. Thirty de novo neoplasias appeared in 22 of 137 transplant recipients between 12 and 104 months after orthotopic liver transplantation (OLT; median follow-up, 69 months): 14 patients had 21 skin cancers, 6 patients had solid-organ cancer, and 3 patients developed a lymphoproliferative disease. Probabilities of de novo neoplasia were 13% at 5 years post-OLT and 26% at 8 years post-OLT. The only associated risk factor for any neoplasia was age. Age and hepatocarcinoma were independent risk factors associated with skin cancer. That hepatocarcinoma in the explanted liver is an independent risk factor for skin cancer suggests there is individual susceptibility to both neoplasias.

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.

This study aims to determine whether the use of a temporary portocaval shunt (PCS) improves hemodynamic and metabolic evolution during orthotopic liver transplantation (OLT). Preservation of the vena cava during OLT has gained wide acceptance. However, benefits of adding a temporary PCS to the piggyback technique during the anhepatic phase in patients with cirrhosis have not been shown. Eighty patients with cirrhosis were studied prospectively. They were randomly distributed into two groups: patients with a temporary PCS (n = 40) and those without a PCS (n = 40). In all cases, the piggyback technique was used. Hemodynamic profiles and biochemical data during OLT and clinical evolution after OLT were evaluated. Preoperative data were similar in both groups. Surgical time also was similar (403 +/- 77 v 387 +/- 56 minutes; P = .3). Red blood cell requirements were lower in the PCS group (2.3 +/- 2.5 v 3.3 +/- 2.9 units), although differences were not significant. In the PCS group, 45% of patients did not need red blood cell transfusion, whereas in the other group, only 22% were not administered a transfusion (P = .03). During the anhepatic phase, the decrease in cardiac output was lower in the PCS group (-9.6% v -19%; P = .05), whereas diuresis during the anhepatic phase was greater in the PCS group (3.6 +/- 2.97 v 2.1 +/- 1.38 mL/kg/h; P = .005). There were no differences in liver biochemical parameters during the first 3 postoperative days. Nevertheless, creatinine levels increased significantly during this period only in the no-PCS group. The use of a temporary PCS during OLT improves hemodynamic status, reduces intraoperative transfusion requirements, and preserves renal function during and after OLT.

Background: The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT)., Methods: Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses., Results: Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001)., Conclusions: Advanced donor age is associated with lower graft and recipient survival.

Biliary complications after orthotopic liver transplantation (OLT) may occur because of preservation injury (PI). In this study, we examine findings on routine reperfusion biopsy specimens in relation to the occurrence of biliary complications and graft outcome. From 1997 to 2000, a total of 193 OLTs were performed in our center. Postreperfusion biopsy specimens were analyzed and histological lesions were graded. For analysis, grafts were grouped into 2 categories: the presence or absence of PI (severe to moderate lesions versus mild or no lesions). Histological evidence of PI was present in 17% of the biopsy specimens. The incidence of grafts with PI and ischemia time longer than 12 hours was 38% compared with 14% in PI and short ischemia time (P =.02). Biliary complications were also more frequent in the PI group (28% v 14%; P =.03). Study of risk factors by means of logistic regression analysis confirmed that the PI group had a greater risk for biliary complications (relative risk, 2.8; 95% confidence interval, 1 to 7.4; P =.03). Moreover, moderate macrovesicular steatosis was found in 6% of the grafts, resulting in a 40% graft loss rate. We found that an increased presence of neutrophilic infiltrates in the postreperfusion biopsy specimen, indicating PI, was related to an increased incidence of biliary complications. Moreover, moderate macrovesicular steatosis was associated with increased graft loss. Therefore, postreperfusion biopsies are useful in anticipating post-OLT complications.

Background: Domino or sequential liver transplantation (DTXL) is a kind of living donor transplant, which was proposed in 1993 and performed for the first time in 1995; later on, more than 45 have been reported. The liver from a patient with familial amyloidotic polyneuropathy(FAP) is used to another patient aged more than 60 with hepatic disease generally cancer, because FAP livers are anatomically and functionally normal except for the synthesis of the systemic TTR variant which only could generate FAP in the recipient after more than 8 years., Patients and Method: The three first cases of DTXL performed in Spain are presented. The donors were FAPTTRMet30 patients from the Major can focus. The first recipient showed severe hyperinsulinism due to metastatic liver from malignant insulinoma; the others had hepatocellular carcinoma on a cirrhotic liver., Results: During the post operatory period liver function of recipients was perfect,and hyperinsulinism disappeared in the first; this patient died after 10 days by sepsis whereas the others showed normal liver function, no recurrent cancer nor onset of FAP. The donors outcome was normal with perfect liver function., Conclusions: Based on our results, in agreement with previous reports, we conclude that DTXH is valid procedure for a selected patient group. In addition they increase the pool of liver donors and therefore diminish the overloaded waiting lists.