A score model for the continuous grading of early allograft dysfunction severity.

Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assign a score for each actual variable value. A model, based on easily obtainable clinical parameters (ie, alanine aminotransferase, international normalized ratio, and bilirubin) and scoring liver function from 0 to 10, was built. The MEAF score showed a significant association with patient and graft survival at 3-, 6- and 12-month follow-ups. Hepatic steatosis and age for donors; cold/warm ischemia times and postreperfusion syndrome for surgery; and intensive care unit and hospital stays, Model for End-Stage Liver Disease and Child-Pugh scores, body mass index, and fresh frozen plasma transfusions for recipients were factors associated significantly with EAD. The model was satisfactorily validated by its application to an independent set of 200 patients who underwent liver transplantation at a different center. In conclusion, a model for the quantitative assessment of EAD severity has been developed and validated for the first time. The MEAF provides a more accurate graft function assessment than current categorical classifications and may help clinicians to make early enough decisions on retransplantation benefits. Furthermore, the MEAF score is a predictor of recipient and graft survival. The standardization of the criteria used to define EAD may allow reliable comparisons of recipients' treatments and transplant outcomes among and within centers.

Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. METHODS: A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients. RESULTS: A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary non-function (n=4). CONCLUSIONS: A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant.

[Current status and future perspectives of hepatocyte transplantation]. / Estado actual y perspectivas futuras del trasplante de hepatocitos.

The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT).Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results.Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment.

Use of aortic extension cuffs for preserving hypogastric blood flow in endovascular aneurysm repair with aneurysmal involvement of common iliac arteries.

BACKGROUND: Intentional hypogastric artery covering during endovascular repair of abdominal aortic aneurysms (EVAR) can carry a non-negligible rate of complications; to preserve pelvic blood flow, several approaches are in use, such as sandwich techniques, branched iliac devices, or the use of aortic extender cuffs in a bell-bottom configuration. We assess the performance of the latter for treatment of common iliac artery aneurysms during EVAR. METHODS: Prospective gathering of data in 21 dilated common iliac arteries (18-25 mm) with coexisting abdominal aorta aneurysm, which were treated from 2005 to 2010 and received a GORE(®) Excluder endograft and one (n = 14) or several aortic extenders in a bell-bottom configuration. Control group consisted of 136 EVARs performed with the same device in the same time frame. Median follow-up was of 47 months, with contrast-enhanced computed tomography assessment 1 month after the procedure and yearly thereafter. RESULTS: Age and comorbidities were homogeneously distributed among groups, although the aortic aneurysm diameter was lower in the bell-bottom group (50 mm vs. 58.2 mm, P < 0.001). There was no 30-day mortality registered in this group, and only one patient died during follow-up (5.3%), without relation with the aneurysmal disease. No significant differences were found in reintervention (15.8% vs. 14.7%, P = 0.707) or endoleak rates (36.8% vs. 38.9%, Fisher P = 1). There were no type I and four type II endoleaks, two of which precised treatment for sac growth. Endoleak-free survival (P = 0.994) and reintervention-free survival (P = 0.563) did not show differences either. CONCLUSION: Bell-bottom technique is a feasible and safe alternative for preserving hypogastric blood flow, and does not imply a higher risk of reintervention or endoleak at 3-year follow-up.

Comparison of results of combined liver-kidney transplantation vs. isolated liver transplantation.

INTRODUCTION: Combined liver-kidney transplantation (LKT) is the best therapeutic option for patients with end-stage liver and kidney disease. OBJECTIVES: To analyze baseline characteristics and clinical outcome of LKT compared to isolated liver transplantation (LT). MATERIAL AND METHODS: The study included 16 LKT performed between 1998 and 2006 and 32 LT matched by age, sex, date and indication for transplantation. Demographic, pretransplant, post-transplant and survival variables were analyzed. RESULTS: As planned by the study design, mean age, distribution by sex and indication for LT were similar between groups. The most common indication for LT was HCV- and/or alcohol-induced cirrhosis. The most common indication for KT was renal failure, in most cases secondary to glomerulonephritis. Twelve patients (69%) were on dialysis before LKT. Hepatocellular carcinoma and diabetes mellitus pre-transplantation were similar between groups. However pretransplant arterial hypertension (AHT) was higher in LKT than LT (50% vs. 19%; p = 0.02). In the post-transplant: reoperation due to bleeding, bacterial infections, liver rejection, AHT and median creatinine levels at 1st and 3rd years were similar in LKT and LT. In contrast, early post-transplant dialysis was higher in LKT than LT (31% vs. 3%; p = 0.01). Survival rates at 1st, 3rd, 5th and 7th years were similar in both groups (87.5%, 74%, 74% and 66% vs. 81%, 75%, 75% and 75% in LT and LKT, respectively). CONCLUSIONS: LKT is an effective therapeutic option in patients with end-stage liver and kidney disease. Most early and late complications and long-term survival are similar to those observed with LT.

[Epithelioid hemangioendothelioma: an uncommon liver tumor]. / Hemangioendotelioma epitelioide: un tumor hepatico infrecuente.

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed.

[Role of resection surgery in breast cancer liver metastases. Experience over the last 10 years in a reference hospital]. / Papel de la resección quirúrgica en las metástasis hepáticas de carcinoma de mama: experiencia en los últimos 10 años en un hospital de referencia.

INTRODUCTION: Breast cancer liver metastases (BCLM) are considered as a systemic disease which is mainly treated with chemotherapy, while the role of surgical resection still remains to be well defined. The aim of the study is to analyse the survival and prognostic factors predictive of mortality in patients with BCLM treated by liver resection. MATERIAL AND METHODS: A total of 21 patients were operated on between 1998-2008, with liver resection being performed on 12. We retrospectively collected several variables. RESULTS: The mean age was 48 years. The most frequent stage was I, with curative surgery in all cases, and the majority (66.7%) received adjuvant treatment. The BCLM were mainly meta metachronic (83.3%). The majority (66.7%) received neoadjuvant treatment. The liver resection was R0 in all cases with no morbidity and a mortality in the long term of 8.3%. Two-thirds received chemotherapy. The estimated survival at one year was 67% and 23% at 5 years. A disease free period of less than 24 months between the primary tumour and the appearance of metastasis was associated with a worse survival. CONCLUSIONS: Resection of BCLM within a multimodal treatment is safe in selected patients.

[Hepatic cell transplantation: a new therapy in liver diseases]. / Trasplante celular hepático: un nuevo tratamiento en las enfermedades hepáticas.

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.

[Indications and results of liver retransplantation: experience with 1181 patients at the University Hospital La Fe]. / Indicaciones y resultados de retrasplante hepático: experiencia del hospital universitario La Fe (1.181 pacientes).

UNLABELLED: Liver retransplantation (LrT) is the only therapeutic option for irreversible failure of a hepatic graft and accounts for 2.9%-24.0% of all liver transplantations (LT). It is technically difficult and has a high level of immediate morbidity and a lower survival than primary LT. Our aim was to determine the rate of LrT and its indications, morbidity, post-operative mortality and actuarial survival in the retransplanted patient. PATIENTS AND METHOD: A historical cohort study of 1181 patients transplanted between 1991 and 2006. RESULTS: Of the 1260 LT performed, 79 were LrT. At the time of the first LT there were no differences between those patients and those that did not require an LrT. The LrT rate was 6.3% and the most frequent causes were: hepatic artery thrombosis (31.6%), recurrence of cirrhosis due the HVC (30.4%) and primary graft (21.5%). The ischemia times, perfusion syndrome and hepatic congestion were no different between the primary LT and the LrT. On the other hand, red cell transfusions were higher in LrT (6.3+/-4.9 vs. 3.5+/-3.0 units, P<0.001). The post-operative morbidity and morbidity (up to 30 days after the LT) was higher in retransplanted patients (68.4% vs. 57.0%, P=0.04 and 25.3% vs. 10.9%, P<0.001; respectively). The actuarial survival at 1 and 5 years was 83% and 69% in those without LrT, 71% and 61% in early LrT and 64% and 34% in delayed LrT (P<0.001). CONCLUSIONS: Despite the increased morbidity and mortality of LrT, it appears that this treatment alternative is still valid in those patients with an early loss of the liver graft. On the other hand, when the graft loss is delayed, it needs to be defined, what would be the minimum acceptable results to indicate LrT and which patients could benefit from this treatment.

Cirrhosis of mixed etiology (hepatitis C virus and alcohol): Posttransplantation outcome-Comparison with hepatitis C virus-related cirrhosis and alcoholic-related cirrhosis.

Hepatitis C virus (HCV)-related liver disease is enhanced by alcohol consumption. Of HCV-related liver transplantation (LT) recipients, 25% have a history of alcohol intake. The purpose of this research was to determine whether LT outcome differs between patients with cirrhosis of mixed etiology compared to HCV or alcohol alone. Of 494 LT (1997-2001), recipient/donor features, post-LT histological, metabolic complications [hypertension, diabetes-diabetes mellitus (DM)], and de novo tumors were compared in 3 groups [HCV-related cirrhosis = 170 (HCV group), alcohol-related cirrhosis (alcohol group) = 107, and cirrhosis of mixed etiology (mixed group) = 60]. Protocol biopsies were done in HCV patients. Severe recurrent HCV disease was defined as: 1-year fibrosis >1, cholestatic hepatitis, recurrent cirrhosis, or HCV-related liver retransplantation (reLT) within 5 years. Patients in the mixed group were younger (mean age: HCV group = 59 years; mixed group = 49 years; alcohol group = 53 years; P < 0.05) and mainly men (% men: HCV group = 51%; mixed group = 97%; alcohol group = 87%). Hepatocellular carcinoma (HCC) was more frequent in HCV patients (HCV group = 44%; mixed group = 35%; alcohol group = 18%; P = 0.05). Five-year survival was lowest in the HCV group (HCV group = 49% versus mixed group = 73% versus alcohol group = 76%; and P < 0.01 for the HCV group versus the alcohol group or the HCV group versus the mixed group; P = 0.74 for the alcohol group versus the mixed group). Metabolic complications and de novo tumors were more frequent in the alcohol groups. Severe HCV disease was similar in the HCV+ groups (HCV group = 45%; mixed group = 45%; P = 0.66). Patients with in the mixed group were more frequently treated with antivirals (32% versus HCV group = 18%; P = 0.03). In HCV patients, factors independently associated with lower survival were older donor age, LT indication (HCV alone), and increased body mass index (BMI). Antiviral therapy was a protective factor. Post-LT survival was lower in the isolated HCV group compared to the alcohol or mixed groups despite a similar recurrence of HCV disease. A greater use of antiviral therapy in the mixed group may explain these differences. The incidence of metabolic complications and de novo tumors was greater in the alcohol groups.

Comparative prospective study of two liver graft preservation solutions: University of Wisconsin and Celsior.

University of Wisconsin solution (UWS) is the gold standard for graft preservation. Celsior solution (CS) is a new solution not as yet widely used in liver grafts. The aim of this study was to compare the liver function of transplanted grafts stored in these 2 preservation solutions. The primary endpoints were the rates of primary nonfunction (PNF) and primary dysfunction (PDF). We performed a prospective and pseudorandomized study that included 196 patients (representing 104 and 92 livers preserved in UWS and CS, respectively) at La Fe University Hospital (Valencia, Spain) between March 2003 and May 2005. PNF and PDF rates, liver function laboratory parameters, postoperative bleeding, vascular and biliary complications, and patient and graft survival at 3 years were compared for the 2 groups. The 2 groups were similar in terms of donor variables, recipient variables, and surgical techniques. The PNF rates were 2.2% and 1.9% in the CS and UWS groups, respectively (P = not significant), and the PDF rates were 15.2% and 15.5% in the CS and UWS groups, respectively (P = not significant). There were no significant differences in the laboratory parameters for the 2 groups, except for alanine aminotransferase levels in month 3, which were lower in the CS group (P = 0.01). No significant differences were observed in terms of complications. Three-year patient and graft survival rates were as follows for years 1, 2, and 3: 83%, 80%, and 76% (patient) and 80%, 77%, and 73% (graft) for the UWS group and 83%, 77%, and 70% (patient) and 81%, 73%, and 67% (graft) for the CS group (P = not significant). In conclusion, this study shows that CS is as effective as UWS in liver preservation.

Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden

Functional assessment of the quality of human hepatocyte preparations for cell transplantation.

Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. Good quality freshly isolated or cryopreserved human hepatocytes are needed for clinical transplantation. However, isolation, cryopreservation, and thawing processes can seriously impair hepatocyte viability and functionality. The aim of the present study was to develop a fast and sensitive procedure to estimate the quality of hepatocyte preparations prior to clinical cell infusion. To this end, cell viability, attachment efficiency, and metabolic competence (urea synthesis and drug-metabolizing P450 activities) were selected as objective criteria. Viability of hepatocyte suspension was estimated by trypan blue staining. DNA content of attached cells 50 min after hepatocyte platting to fibronectin/collagen-coated dishes was quantified to estimate adherence capacity. Urea production was determined after incubating hepatocyte suspensions with 2 mM C1NH4 for 30 min. The cytochrome P450 function was assayed by a 30-min incubation of hepatocyte suspension with a cocktail mixture containing selective substrates for seven individual P450 activities (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4). The assay can be applied to both freshly isolated and cryopreserved hepatocyte suspensions, and the results are available within 1 h, which could help to make short-term decisions: 1) to assess the suitability for cell transplantation of a preparation of freshly isolated hepatocytes or a particular batch of thawed cells, or 2) to estimate the convenience of banking a particular cell preparation.

Hepatocyte transplantation program: Lessons learned and future strategies.

This review aims to share the lessons we learned over time during the setting of the hepatocyte transplantation (HT) program at the Hepatic Cell Therapy Unit at Hospital La Fe in Valencia. New sources of liver tissue for hepatocyte isolation have been explored. The hepatocyte isolation and cryopreservation procedures have been optimized and quality criteria for assessment of functionality of hepatocyte preparations and suitability for HT have been established. The results indicate that: (1) Only highly viable and functional hepatocytes allow to recover those functions lacking in the native liver; (2) Organs with steatosis (≥ 40%) and from elderly donors are declined since low hepatocyte yields, viability and cell survival after cryopreservation, are obtained; (3) Neonatal hepatocytes are cryopreserved without significant loss of viability or function representing high-quality cells to improve human HT; (4) Cryopreservation has the advantage of providing hepatocytes constantly available and of allowing the quality evaluation and suitability for transplantation; and (5) Our results from 5 adults with acute liver failure and 4 from children with inborn metabolic diseases, indicate that HT could be a very useful and safe cell therapy, as long as viable and metabolically functional human hepatocytes are used.

Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts.

A major problem for the isolation and transplantation of hepatocytes is the lack of resources for obtaining viable hepatocytes. Improving this situation would enhance hepatic cell transplantation programs. Our objective was to evaluate the influence of the preservation solutions used during organ retrieval on the quality of hepatocytes isolated from liver tissue. We compared the results of the collagenase perfusion technique for isolation of hepatocytes in human livers flushed with University of Wisconsin (UW) and Celsior preservation solutions. Yield (number of viable cells per gram of tissue), cellular viability, efficiency of cells to attach to culture plates and form a monolayer, and drug metabolizing competence of the hepatocytes were measured. Successful isolation was achieved in 63% of the procedures using the UW solution and 100% of the procedures using the Celsior solution. In the UW group, significantly lower cell viability (38 +/- 41% vs. 79 +/- 14%, p < 0.05), yield of cells (4.0 +/- 5.2 x 10(6) vs. 8.2 +/- 5.6 x 10(6) cells/g, p < 0.05), and protein content at 24 h of culture (0.6 +/- 0.6 vs. 1.2 +/- 0.3 mg protein per plate, p < 0.05) than in Celsior solution were found. However, similar values of P450 activities were found in both groups. The more successful isolation, better yield, and higher cell viability obtained from human liver grafts preserved in Celsior solution, in comparison to UW solution, suggest Celsior solution as the most appropriate for preserving cadaveric hepatic tissue to be used for hepatocyte harvesting.

Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

Neonatal livers: a source for the isolation of good-performing hepatocytes for cell transplantation.

Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. However, the supply of hepatocytes is limited given the shortage of organs available to isolate good-functioning quality cells. Neonatal livers may be a potential source alternative to adult livers to obtain good-performing hepatic cells for hepatocyte transplantation, which has not yet been explored profoundly. High-yield preparations of viable hepatocytes were isolated from 1- to 23-day-old liver donors, cryopreserved, and banked. Cell integrity and functional quality assessment were performed after thawing. Neonatal hepatocytes showed better postthawing recovery compared with adult hepatocytes, as shown by the viability values that did not differ significantly from freshly isolated cells, a higher expression of adhesion molecules (ß1-integrin, ß-catenin, and E-cadherin), better attachment efficiency, cell survival, and a lower number of apoptotic cells. The metabolic performance of thawed hepatocytes has been assessed by ureogenesis and drug-metabolizing capability (cytochrome P450 and UDP-glucuronosyltransferase enzymes). CYP2A6, CYP2C9, CYP2E1, and CYP3A4 activities were found in all cell preparations, while CYP1A2, CYP2B6, CYP2C19, and CYP2D6 activities were detected only in hepatocytes from a few neonatal donors. The expression of UGT1A1 and UGT1A9 (transcripts and protein) was detected in all hepatocyte preparations, while activity was measured only in some preparations, probably due to lack of maturity of the enzymes. However, isoforms UGT1A6 and UGT2B7 showed considerable activity in all preparations. Compared to adult liver, the hepatocyte isolation procedure in neonatal livers also provides thawed cell suspensions with a higher proportion of hepatic progenitor cells (EpCAM(+) staining), which could also participate in regeneration of liver parenchyma after transplantation. These results could imply important advantages of neonatal hepatocytes as a source of high-quality cells to improve human hepatocyte transplantation applicability.

[Hepatic cell transplantation. Technical and methodological aspects]. / Trasplante celular hepático. Aspectos técnicos y metodológicos.

Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient. There are established protocols for the isolation of human hepatocytes from unused segments of donor livers, based on collagenase digestion of cannulated liver tissue at 37 degrees C. The hepatocytes can be used fresh or cryopreserved. Cryopreservation of isolated human hepatocytes would then be available for planned use. In cell transplant, the important aspects are: infusion route, number of cells, number of infusions and viability of the cells. The cells are infused into the patient through a catheter inserted via portal vein or splenic artery. Liver cell transplantation allows liver tissue to be used that would, otherwise, be discarded, enabling multiple patients to be treated with hepatocytes from a single tissue donor.

Effect of calcineurin inhibitors in the outcome of liver transplantation in hepatitis C virus-positive recipients.

BACKGROUND: There is a paucity of good studies evaluating the impact of calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)-infected liver transplant (LT) recipients. METHODS: We sought to determine whether there are differences on posttransplantation survival and histologic recurrence in HCV-LT recipients based on initial immunosuppression (IS) by conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine-based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies were performed. RESULTS: Baseline characteristics (demographics, liver function at LT, genotype distribution, donor, surgery, and IS except for the type of calcineurin inhibitor) did not differ between groups. Severe disease (defined as bridging fibrosis, cirrhosis, cholestatic hepatitis, or allograft loss or death because of recurrent disease in the first year) was present in 67 of 253 (26.5%) and was equally distributed in the CsA and Tac groups (27% vs. 26%; P=0.68). Two thirds of protocol biopsies performed at 1 year showed some fibrosis without differences between CsA and Tac groups (75% vs. 70%). Advanced fibrosis (bridging fibrosis and cirrhosis) was diagnosed in 30% CsA and 24.5% Tac patients (P=NS). No differences in survival at 1 and 7 years were observed (83% and 67% vs. 78% and 64%, respectively, P=0.4). In summary, in patients undergoing LT for HCV-related liver disease, posttransplantation outcome is not related to the calcineurin inhibitor used.

Step-by-step isolated resection of segment 1 of the liver using the hanging maneuver.

The caudate lobe can be the origin of primary liver tumours or the sole site of liver metastases. This lobe is anatomically divided into 3 parts: Spiegel's lobe (Couinaud's segment 1), paracaval portion (Couinaud's segment 9), and the caudate process. In this series of 4 cases, we provide a step-by-step description of a surgical technique variation that can be applied to resections of lesions localized in segment 1. We believe that other than size, lesion removal in this hepatic anatomic area, which is difficult to perform, can be done more easily using this new approach because it requires minimal mobilization without unnecessary parenchyma transection of other liver parts. Therefore, it reduces the risk of lesions in the inferior vena cava and the middle hepatic vein and respects adequate margins without the use of clamping maneuvers and in an acceptable surgical time.