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Summary: Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part attributed to the lifelong administration of immunosuppression and its associated side effects. Several studies reported in the last decades have evaluated the impact of immunosuppression minimization in liver transplant recipients, but results have been inconsistent due to the heterogeneity of study designs and insufficient sample sizes. On the other hand, complete immunosuppression withdrawal has proven to be feasible in approximately 20% of carefully selected liver transplant recipients, especially in older patients and those with longer duration after transplantation. The long-term risks and clinical benefits of this strategy, however, also need to be clarified. As a consequence, and despite the general perception that a large proportion of liver recipients are over-immunosuppressed, it is currently not possible to derive evidence-based guidelines on how to manage long-term immunosuppression to improve clinical outcomes. Large clinical trials of drug minimization and/or withdrawal focused on clinically-relevant long-term outcomes are required. Development of personalized medicine tools and a deeper understanding of the pathogenesis of idiopathic inflammatory graft lesions will be pre-requisites to achieve these goals. [ABSTRACT FROM AUTHOR]

Background/Aims: The applicability of adult-to-adult living donor liver transplantation has not been established yet. We report the first data in a European center of the process leading to this procedure from the first moment the patients were informed about it. Methods: In phase 1 of the process, 121 adult patients enlisted for cadaveric liver transplantation and their relatives were informed of the technical aspects, advantages and risks of living donor liver transplantation, and the essential criteria for living donation. In phase 2, potential donors identified in phase 1 were evaluated in depth. Results: Twenty-one (17%) patients underwent living donor liver transplantation. This procedure was not performed in 60 patients (50%) for reasons concerning the patients themselves, especially their refusal to receive living donor liver transplantation from a relative (30%). Forty patients (33%) did not undergo living donor liver transplantation for reasons concerning potential donors: donors were not identified (14%), declined the donation (13%), or were refused for technical reasons (6%). The expected waiting time to transplantation was longer in patients who underwent living donor liver transplantation than in those who did not. Conclusions: The applicability of adult-to-adult living donor liver transplantation is low, mainly because of reasons related to potential recipients. [Copyright &y& Elsevier]

A correction to the article "Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: A prospective cohort study" in the 2015 issue is presented.

Objectives: IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting.Methods: Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks.Results: Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events.Conclusions: IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population. [ABSTRACT FROM AUTHOR]

Background & Aims Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. Methods All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. Results Median time since transplantation to liver biopsy was 13 years (10–22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis. Conclusions A large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients’ liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage. Lay summary A large proportion of adult liver transplant recipients who survive for a long time exhibit subclinical histological abnormalities. The expression profile (a measurement of the activity of genes) of liver tissue from a large fraction of these patients closely resembles the profile of T cell mediated rejection. Liver allografts showing the highest expression levels of rejection-related genes developed progressive damage over time. [ABSTRACT FROM AUTHOR]

The mayor goal still outstanding into the solid organ transplantation field involves the search of surrogate biomarkers able to predict several clinical events, such as acute rejection (AR) or opportunistic infection. In the present multicenter study, a series of interesting surface antigens with important activator or inhibitory immune functions on cultured peripheral T cells were monitored in liver transplant recipients drawn at baseline and up to one year after transplantation. Sixty-four patients were included in the multicenter study during 3 years. Pre- and post-transplantation surface antigens levels displayed significant differences between AR and non acute rejection (NAR) groups, and also this differential expression was used to construct a risk predictive model based on a composite panel of outcome biomarkers (CD38, CD69, CD95 and CD154). The model was able to stratify these patients at high risk of AR. These preliminary results could provide basic information to improve the immunosuppressive treatment and it might better help to predict AR episodes. [ABSTRACT FROM AUTHOR]

Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4+CD25highCD45RO+CD62L+) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year posttransplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury (IRI) leads to significant tissue damage in liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proved their effectiveness against IRI. The objective of our study was to investigate the potential protective effects of intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) in steatotic livers subjected to cold ischemia reperfusion. In this study, we used isolated perfused rat liver model to assess the effects of PEG 35 intravenous administration after prolonged cold ischemia (24 h, 4°C) and after reperfusion (2 h, 37°C). Liver injury was measured by transaminases levels and mitochondrial damage was determined by confocal microscopy assessing mitochondrial polarization (after cold storage) and by measuring glutamate dehydrogenase activity (after reperfusion). Also, cell signaling pathways involved in the physiopathology of IRI were assessed by western blot technique. Our results show that intravenous administration of PEG 35 at 10 mg/kg ameliorated liver injury and protected the mitochondria. Moreover, PEG 35 administration induced a significant phosphorylation of prosurvival protein kinase B (Akt) and activation of cytoprotective factors e-NOS and AMPK. In conclusion, intravenous PEG 35 efficiently protects steatotic livers exposed to cold IRI. [ABSTRACT FROM AUTHOR]

Summary Liver transplantation is increasingly performed in selected HIV-infected patients in most developed countries, with excellent results reported in patients with liver diseases unrelated to HCV. In contrast, survival in HCV/HIV-coinfected liver recipients is poorer than in HCV-monoinfected patients, due to more aggressive recurrence of HCV and consequent graft loss and death. Results from American, French, and Spanish cohort studies showed a 5-year survival rate of only 50–55%. Therefore, it is debated whether liver transplantation should be offered to HCV/HIV-coinfected patients. Studies have shown that the variables more consistently associated with poor outcome are: (1) the use of old or HCV-positive donors, (2) dual liver-kidney transplantation, (3) recipients with very low body mass index and (4) less site experience. However, the most effective factor influencing transplantation outcome is the successful treatment of HCV recurrence with anti-HCV. Survival is 80% in patients whose HCV infection resolves. Unfortunately, the rates of sustained virological response with pegylated-interferon plus ribavirin in coinfected recipients are low, particularly for genotype 1 (only 10%). Here we present a non-systematic review of the literature based on our own experience in different liver transplant scenarios. This review covers selection criteria in HIV-infected patients, pre- and post-LT management, donor selection, anti-HCV treatment, drug interactions with antiretrovirals and anti-HCV direct antiviral agents, hepatocellular carcinoma, and liver retransplantation. Recommendations are rated. Finally, we explain how the introduction of new effective and more tolerable direct antiviral agents may improve significantly the outcome of HCV/HIV-coinfected liver recipients. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion ( IR) injury is an important problem in liver surgery especially when steatosis is present. Ischemic preconditioning ( PC) is the only surgical strategy that has been applied in patients with steatotic livers undergoing warm ischemia. Silent information regulator 1 ( SIRT1) is a histone deacetylase that regulates various cellular processes. This study evaluates the SIRT1 implication in PC in fatty livers. Homozygous (Ob) Zucker rats were subjected to IR and IR + PC. An additional group treated with sirtinol or EX527 ( SIRT1 inhibitors) before PC was also realized. Liver injury and oxidative stress were evaluated. SIRT1 protein levels and activity, as well as other parameters involved in PC protective mechanisms (adenosine monophosphate protein kinase, e NOS, HSP70, MAP kinases, apoptosis), were also measured. We demonstrated that the protective effect of PC was due in part to SIRT1 induction, as SIRT1 inhibition resulted in increased liver injury and abolished the beneficial mechanisms of PC. In this study, we report for the first time that SIRT1 is involved in the protective mechanisms induced by hepatic PC in steatotic livers. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study is to investigate the protective mechanisms induced by bortezomib added to Institut George Lopez ( IGL)-1 preservation solution to protect steatotic livers against cold ischaemia reperfusion injury and to examine whether these mechanisms occur through the activation of adenosine monophosphate activated protein kinase ( AMPK), Akt/ mTOR pathways. Methods Steatotic livers from obese rats were preserved for 24 h (at 4° C) in IGL-1 solution with or without bortezomib (100 n M) or pretreated with AMPK inhibitor adenine 9-α- D-arabinofuranoside and preserved in IGL-1 + bortezomib. Livers were then perfused for 2 h at 37°C. Liver injury (alanine aminotransferase/aspartate aminotransferase) and function (bile production and vascular resistance) were measured. Also, Akt/ mTOR, phosphorylated AMPK ( pAMPK) and apoptosis were determined by Western blot analyses. Key findings Bortezomib addition to IGL-1 solution significantly reduced steatotic liver injury, improved graft function and decreased liver apoptosis. These benefits were diminished by the pretreatment of obese rats with AMPK inhibitor Ara. Western blot analyses showed a significant increase in pAMPK after ischaemia and reperfusion. We also observed a significant phosphorylation of Akt in IGL-1 + bortezomib group that, in turn, induced the phosphorylation of mTOR and glycogen synthase kinase 3β. Conclusions Bortezomib, at low and non toxic concentration, is a promising additive to IGL-1 solution for steatotic liver preservation. Its protective effect is due to the activation of AMPK and Akt/ mTOR pathways. [ABSTRACT FROM AUTHOR]

Abstract: Background: The dramatic shortage of organs leads to consider the steatotic livers for transplantation although their poor tolerance against ischemia reperfusion injury (IRI). Ubiquitin proteasome system (UPS) inhibition during hypothermia prolongs myocardial graft preservation. The role of UPS in the liver IRI is not fully understood. Bortezomib (BRZ) treatment at non-toxic doses of rats fed alcohol chronically has shown protective effects by increasing liver antioxidant enzymes. We evaluated and compared both proteasome inhibitors BRZ and MG132 in addition to University of Wisconsin preservation solution (UW) at low and non-toxic dose for fatty liver graft protection against cold IRI. Experimental: Steatotic and non-steatotic livers have been stored in UW enriched with BRZ (100nM) or MG132 (25μM), for 24h at 4°C and then subjected to 2-h normothermic reperfusion (37°C). Liver injury (AST/ALT), hepatic function (bile output; vascular resistance), mitochondrial damage (GLDH), oxidative stress (MDA), nitric oxide (NO) (e-NOS activity; nitrates/nitrites), proteasome chymotrypsin-like activity (ChT), and UPS (19S and 20S5 beta) protein levels have been measured. Results: ChT was inhibited when BRZ and MG132 were added to UW. Both inhibitors prevented liver injury (AST/ALT), when compared to UW alone. BRZ increased bile production more efficiently than MG132. Only BRZ decreased vascular resistance in fatty livers, which correlated with an increase in NO generation (through e-NOS activation) and AMPK phosphorylation. GLDH and MDA were also prevented by BRZ. In addition, BRZ inhibited adiponectin, IL-1, and TNF alpha, only in steatotic livers. Conclusion: MG132 and BRZ, administrated at low and non toxic doses, are very efficient to protect fatty liver grafts against cold IRI. The benefits of BRZ are more effective than those of MG132. This evidenced for the first time the potential use of UPS inhibitors for the preservation of marginal liver grafts and for future applications in the prevention of IRI. [Copyright &y& Elsevier]

Background: Few studies have studied the effects of graft quality on non-urgent liver retransplantation (ReLT) outcomes. We aimed to analyze graft characteristics and survival in non-urgent ReLT and the effect of using grafts with extended criteria on survival. Methods: Eighty non-urgent ReLT were performed from June 1988 to June 2010. The whole series was divided by identical time periods to study time-related effects. We assessed graft quality with donor risk index (DRI) and Briceño scores and recipient status with the Model for End-stage Liver Diseases and Rosen scores. Low and high-risk grafts were defined by a DRI cutoff of 1.8. Results: Graft survival was similar in both periods (1-, 5-, and 10-year graft survivals: 73.5, 46.9, and 40.8 versus 71, 47.7, and 47.7%, p = 0.935) although donor quality was worse in the second period (DRI: 1.35 ± 0.32 vs. 1.66 ± 0.34, p < 0.001). In the first period high-risk grafts did worse than low-risk grafts (5-year survival: 0 vs. 54.5%, p = 0.002) while in the second period outcomes were similar (5-year survival: 48.6 vs. 56.7 %, p = 0.660). Donor age was the only independent donor factor for graft survival, with lower survival when using grafts from donors over 60-years-old. Conclusions: Graft quality in ReLT has worsened with time mainly because of older donors but nowadays the use of high-risk grafts in non-urgent ReLT is not associated with worse graft survival because of better perioperative management. Moreover of being selective on recipient conditions, care should be taken when using grafts from donors over 60-years-old for non-urgent ReLT. [ABSTRACT FROM AUTHOR]

Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intragraft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with nontolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver steatosis enhances ischemia/reperfusion (I/R) injury and is considered a primary factor in graft failure after liver transplantation. Although previous reports have shown a role for qualitative steatosis (macrovesicular vs. microvesicular) in hepatic I/R injury, no studies have compared side by side the specific contribution of individual lipids accumulating in fatty liver to I/R damage. Methods: We used nutritional and genetic models of micro and macrovesicular fatty livers exhibiting specific lipid profiles to assess their susceptibility to normothermic I/R injury. Results: Unlike choline-deficient (CD) diet-fed mice, characterized by predominant liver triglycerides/free fatty acids (TG/FFA) accumulation, mice fed a cholesterol-enriched (HC) diet, which exhibited enhanced hepatic cholesterol loading in mitochondria, were highly sensitive to I/R-induced liver injury. In vivo two-photon confocal imaging revealed enhanced mitochondrial depolarization and generation of reactive oxygen species following hepatic I/R in HC-fed but not in CD-fed mice, consistent with decreased mitochondrial GSH (mGSH) observed in HC-fed mice. Moreover, ob/ob mice, characterized by increased hepatic TG, FFA, and cholesterol levels, were as sensitive to I/R-mediated liver injury as mice fed the HC diet. Livers from ob/ob mice displayed increased StAR expression and mitochondrial cholesterol accumulation, resulting in mGSH depletion. Interestingly, atorvastatin therapy or squalene synthase inhibition in vivo attenuated StAR overexpression, mitochondrial cholesterol loading, and mGSH depletion, protecting ob/ob mice from I/R-mediated liver injury. Conclusions: Cholesterol accumulation, particularly in mitochondria, sensitizes to hepatic I/R injury, and thus represents a novel target to prevent the enhanced damage of steatotic livers to I/R-mediated damage. [Copyright &y& Elsevier]

Abstract: Biomarkers that reflect immune response recovery and predict clinical events during withdrawal or minimization of immunosuppressive therapy have not been evaluated. This study aimed to evaluate whether immune response recovers after withdrawal of long-term immunosuppressive treatment in stable liver transplant patients and to determine whether specific biomarkers reflect immune response reactivity and predict rejection. Pharmacokinetic–pharmacodynamic profiles were determined in 24 patients and 80 healthy donors before immunosuppressive treatment reduction began, at 50%, and at complete withdrawal. In patients who rejected, effector-T-cell response mediated by soluble IFN-γ, %CD4+IFN-γ and %CD8+IL-2/IFN-γ were significantly increased, while TGF-β1 production and the TGF-β1/IFN-γ ratio were significantly decreased. In patients with rejection, soluble IFN-γ and %CD8+IL-2 were significantly higher before immunosuppressive treatment was reduced. Further studies are required, but this battery of biomarkers performed in whole blood could be a useful tool to monitor immunosuppressive treatment minimization or withdrawal protocols and identify patients at increased risk of rejection. [Copyright &y& Elsevier]

γδ T cells are innate-type lymphocytes that preferentially act as regulators of local effector immune responses. Recent reports found an altered distribution of the two main subpopulations of blood γδ T cells (Vδ1 and Vδ2) in operationally tolerant liver transplant recipients. Based on this, γδ T cells subset quantification was proposed as a biomarker of immunologic risk in liver transplantation. The specific characteristics of γδ T cell subsets in transplantation remain however unknown. We have investigated here the phenotype, repertoire and functional properties of γδ T cell subsets in a large population of allograft recipients. Our results indicate that alterations in the γδ T cell compartment are not restricted to tolerant liver recipients. In fact, most immunosuppressed liver and kidney recipients also display an enlarged peripheral blood γδ T cell pool mainly resulting from an expansion of Vδ1 T cells exhibiting an oligoclonal repertoire and different phenotypic and cytokine production traits than Vδ2 T cells. We propose that persistent viral infections are likely to contribute to these alterations. Our data provide novel insight in the biology of γδ T cells and a rationale for exploring these lymphocytes in more depth into the pathogenesis of viral infections in transplantation. [ABSTRACT FROM AUTHOR]

A rapid, sensitive, and specific method was developed and validated using liquid chromatography-tandem mass spectrometry for the simultaneous quantitation of atorvastatin (ATV) and its major metabolite ortho-hydroxyatorvastatin ( o-HATV) in human plasma. The sample preparation involved a liquid–liquid extraction without chlorinated solvents and an on-line solid-phase extraction exploring the possibilities that anion exchange offers. The analytical method presented intraday and day-to-day variation below 10%; intraday and day-to-day accuracy stood between 94% and 105%; the limit of quantification was 0.1 ng/mL for ATV and 0.5 ng/mL for o-HATV; and the recovery was above 75% for both molecules. This method was applied successfully to quantitate ATV and o-HATV concentrations in an unstudied renal transplant recipient cohort treated with an immunosuppressive regime of tacrolimus and mycophenolic acid and a cohort of hypercholesterolemic patients included in the study as a control group. It can be used to evaluate patient adherence, drug–drug interactions, and pharmacokinetic/pharmacodynamic relationships. The results in our study showed that ATV and o-HATV levels in the renal transplant group were significantly increased ( p < 0.001), compared to the hypercholesterolemic group. [ABSTRACT FROM AUTHOR]

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation. [ABSTRACT FROM AUTHOR]

The article examines whether pharmacologic strategies blocking angiotensin II actions protect steatotic livers against ischemia-reperfusion (I/R) injury. According to the authors, the study showed that pharmacologic blockers of angiotensin II action increased bradykinin generation in steatotic livers after I/R injury.

Background/Aims: Serum sodium predicts prognosis in cirrhosis and may improve the prognostic accuracy of the model for end-stage liver disease (MELD) score, but the available information is limited. The aim of the present study was to assess the prognostic value of serum sodium in the prediction of survival at 3 and 12 months after listing in patients with cirrhosis awaiting liver transplantation, and to compare its predictive value with that of the MELD score. Patients and methods: 308 consecutive patients with cirrhosis listed for transplantation during a 5-year period were included in the study. The end-point was survival at 3 and 12 months before transplantation. Variables obtained at the time of listing were analysed for prognostic value using multivariable analysis. Accuracy of prognostic variables was analysed by receiver operating characteristic (ROC) curves. Results: The MELD score and serum sodium concentration were the only independent predictors of survival at 3 and 12 months after listing. Low serum sodium was associated with an increased risk of death in all subpopulations of patients with cirrhosis categorised according to the major complication developed before listing. The area under the ROC curves for serum sodium and MELD score was not significantly different both at 3 months (0.83 vs 0.79, respectively) and at 12 months (0.70 vs 0.77, respectively). The addition of serum sodium did not significantly improve the accuracy of the MELD score in the prediction of survival at 3 and 12 months. Conclusion: In patients with cirrhosis awaiting liver transplantation, serum sodium and MELD were found to be independent predictors of survival. Larger studies are needed to determine whether the addition of serum sodium to MELD can improve its prognostic accuracy. [ABSTRACT FROM AUTHOR]

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 g/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. [ABSTRACT FROM AUTHOR]

Background: Pretransplant renal function is the major determinant of survival after liver transplantation (LTx). Patients with hepatorenal syndrome (HRS) have a poor outcome after LTx compared with patients transplanted without HRS.Aim: To analyze the impact of treatment of HRS before LTx on outcome after transplantation.Methods: The outcome of patients with HRS (n=9) treated with vasopressin analogues before LTx was compared with that of a contemporary control group of patients without HRS (n=27) matched by age, severity of liver failure, and type of immunosuppression.Results: Cases and controls were similar with respect to pretransplantation characteristics. Three-year survival probability was similar between the two groups (HRS-treated: 100% vs control: 83%, P=0.15). No significant differences were found between the two groups with respect to the incidence of impairment of renal function after LTx (HRS-treated: 22% vs control: 30%), severe infections (22 vs 33%), acute rejection (33 vs 41%), days in Intensive Care Unit (6±1 vs 8±1), days in hospital (27±4 vs 31±4), and transfusion requirements (11±3 vs 10±2 units).Conclusions: Patients with HRS treated with vasopressin analogues before LTx have a posttransplantion outcome similar to that of patients transplanted with normal renal function. These results suggest that HRS should be treated before LTx. [Copyright &y& Elsevier]

Background/Aims: After liver transplantation (LT) infection of the graft with the hepatitis C virus (HCV) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients. One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT.Methods: We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in 30 HCV-cirrhotic patients awaiting LT. At the time of inclusion 15 patients were Child–Pugh A and 15 Child–Pugh B/C. The infecting genotype was 1b in 25 patients. Treatment with interferon α-2b 3 MU/day and ribavirin 800 mg/day was initiated when the expected time for LT was less than 4 months and continued until LT. The median duration of treatment was 12 weeks.Results: Nine patients (30%) achieved a virological response and 21 did not respond to therapy. In nine (43%) of the 21 non-responders viral load decreased \ge 2 log10 during treatment. A viral load decrease \ge 2 log10 at week 4 of treatment was the strongest predictor of virological response. All nine virological responders have already undergone LT; six patients remain free of infection after a median follow-up of 46 weeks and HCV infection recurred in three patients after LT. In one of these patients HCV-RNA was still detectable in the explanted liver. Side effects were frequent and dose reduction was necessary in 19 (63%) of the 30 patients; no patient died while on therapy.Conclusions: Our data support the utilization of antiviral therapy in HCV-infected patients awaiting LT as one of the strategies to prevent hepatitis C recurrence after transplantation. [Copyright &y& Elsevier]