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While outcome continuously improves after liver transplantation, sepsis remains the leading cause of early postoperative mortality. Diagnosis of infections remains particularly difficult in these patients. This study used plasma profiling coupling Proteinchip array with surface-enhanced laser desorption ionization time-of-fly mass spectrometry to search for biomarkers of postoperative sepsis in patients who underwent liver transplantation.Diagnosis of sepsis at day 5 relied on widely accepted clinical signs and positive culture of microbiologic samples. Profiles of day 5 plasma were obtained from SELDI-TOF CM10 chip (BioRad, Marnes-la-Coquette, France) analysis. Mean peak intensity of proteins was compared between septic and nonseptic plasma by U test followed by analysis of the area under the receiver-operating characteristic for the significant peaks. Diagnostic performance of significant proteins was established in a derivation set and in a validation set.In the derivation set of 31 patients with and 30 without infection, 23 plasma protein peaks were differentially expressed between patients with and without sepsis. Combination of five peaks allowed sepsis diagnosis with a positive likelihood ratio of 12.5 and a C-statistics of 0.72, 95% CI 0.57-0.85. In the validation set of 31 patients with infection and 34 without infection, the five peaks were differentially expressed as well and allowed day 5 sepsis diagnosis with a positive likelihood ratio of 5.1 and C-statistics of 0.74 (0.58-0.85).A combination of five plasma protein peaks may provide material for useful diagnostic biomarkers of postoperative sepsis in patients undergoing liver transplantation. However, these proteins remain to be identified.

Background/objective: Little is known on the morphological changes in the kidneys of cirrhotic patients with abnormal urinalysis and/or high serum creatinine levels. This retrospective, one-point-in-time study aimed to report the results of the analysis of renal biopsy specimens obtained in patients with cirrhosis. Methods: We retrieved information on 65 patients who underwent transvenous renal biopsy for proteinuria >0.5 g/day and/or microscopic haematuria and/or unexplained renal impairment (defined by serum creatinine levels >1.5 mg/dl). Results: Fifty-one per cent of the patients had proteinuria >0.5 g/day, 58% had haematuria and 83% had renal impairment. Renal biopsy disclosed injury to glomeruli in 77% of the patients, to vessels in 69% and to the tubulointerstitium system in 94% (chronic in 77%; acute in 75%). Fibrous endarteritis was the most common renal vascular lesion. Injuries to different structures were frequently combined. Isolated glomerular alterations were found in only two patients. Acute tubular necrosis was significantly more common in patients with fibrous endarteritis than in those without. Among 18 patients with renal impairment, proteinuria

The MELD score has shown that, besides markers of liver function, serum creatinine has a strong prognostic value in cirrhosis. However, even though creatinine has a good prognostic value, it is an inaccurate marker of renal function in cirrhosis. Creatinine and creatinine-based equations tend to overestimate glomerular filtration rate (GFR), and creatinine clearance from timed urine collection also overestimates GFR. Hence, clearance of exogenous markers such as iohexol remains the only reliable method for assessing precisely GFR in cirrhosis. Whereas these investigations are limited by their costs and complexity, and they can hardly be repeated at short intervals, serum cystatin C could be an alternative, although it needs further validation. Accurate markers and/or specific equations are therefore still needed to assess GFR in cirrhotic patients. Pre-renal failure and hepatorenal syndrome (HRS) are the main causes of acute renal failure in cirrhosis. Both result from decreased renal blood flow and both can result in acute tubular necrosis. HRS is not always fully reversible with liver transplantation possibly due to underlying chronic kidney damage. A number of cirrhotic patients with acute renal failure may also have chronic kidney damage (“acute-on-chronic renal failure”); furthermore, cirrhotic patients frequently have co-morbidities such as diabetes that may result in chronic impairment in renal function. Since conventional urinary markers are biased in cirrhosis, a biopsy is the only way to document and quantify renal lesions; moreover, transvenous route should be preferred to percutaneous route. In candidates for transplantation, attention should therefore be focused on vascular lesions which may represent a risk factor for nephrotoxicities induced by calcineurin-inhibitors.

Patients with Budd-Chiari syndrome can present with acute, subacute, or chronic disease; the definitions and significance of these variants have been disputed. An increased level of serum alanine aminotransferase (ALT) is an objective marker for acute liver injury. We analyzed the significance of changes in ALT levels in Budd-Chiari syndrome patients.We performed a retrospective analysis of data from 96 consecutive Budd-Chiari syndrome patients.A threshold peak ALT level that was 5-fold the upper limit of normal distinguished 2 groups of patients: patients with high levels of ALT (40% of patients) presented with more severe liver disease, less frequent liver fibrosis, and more frequent liver cell necrosis, compared with those with ALT levels below this threshold. Patients with levels of ALT that started out high but slowly declined (50% of starting concentration within 3 days) had significantly lower odds of survival than those with a rapid decline and those with low levels of ALT (40 months transplantation-free survival, 31%, 63%, and 71%, respectively). When ALT level and the velocity of its decline are used as criterion, these data add significant prognostic information to Child-Pugh, to Clichy, and to Rotterdam Budd-Chiari syndrome scores.Determination of ALT levels at patient presentation allows 2 variants of Budd-Chiari syndrome to be distinguished. High levels of ALT reflect acute, severe, but potentially reversible, ischemic liver cell necrosis. High levels of ALT that decrease slowly predict a poor outcome for patients and might justify rapid aggressive management.

Portal vein thrombosis is a relatively common finding during liver transplantation. The management of portal vein thrombosis during liver transplantation is technically demanding and ensures adequate portal flow to the liver graft. Eversion thromboendovenectomy and bypass using a patent splanchnic vein and cavoportal hemitransposition are the most often used procedures to treat portal vein thrombosis. There have been anecdotal reports of portal vein arterialization. We report a case of portal vein arterialization during orthotopic liver transplantation for decompensated cirrhosis. When thromboendovenectomy failed to restore sufficient portal flow and completion of arterial anastomosis between the recipient hepatic artery and the donor celiac trunk, a calibrated end-to-side anastomosis between the donor splenic artery and the donor portal vein was performed. With a 6-year follow-up, there are no symptoms related to portal hypertension, liver function is normal. However, an aneurismal dilatation of the portal branches has progressively developed. Calibrated portal vein arterialization is a possible option for portal vein thrombosis in liver transplantation, allowing long-term patient and graft survival.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.

To analyse the characteristics of and the factors associated with the development of hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS).97 consecutive patients with BCS and a follow-upor = 1 year were evaluated retrospectively. Liver nodules were evaluated using serum alpha-fetoprotein (AFP) level and imaging features (CT/MRI). Biopsy of nodules was obtained when one of the following criteria was met: numberor = 3, diameteror = 3 cm, heterogeneity, washout on portal venous phase, increase in size on surveillance, or increase in AFP level.Patients were mainly Caucasian (69%) and female (66%). Mean age at the diagnosis of BCS was 35.8 (SE 1.2 years), and median follow-up 5 years (1-20 years). The inferior vena cava (IVC) was obstructed in 13 patients. Liver nodules were found in 43 patients, 11 of whom had HCC. Cumulative incidence of HCC during follow-up was 4%. Liver parenchyma adjacent to HCC showed cirrhosis in nine patients. HCC was associated with male sex (72.7% v 29.0%, p = 0.007); factor V Leiden (54.5% v 17.5%, p = 0.01); and IVC obstruction (81.8% v 4.6%, p0.001). Increased levels of serum AFP were highly accurate in distinguishing HCC from benign nodules: PPV = 100% and NPV = 91% for a cut-off level of 15 ng/ml.The incidence of HCC in this large cohort of BCS patients was similar to that reported for other chronic liver diseases. IVC obstruction was a major predictor for HCC development. Serum AFP appears to have a higher utility for HCC screening in patients with BCS than with other liver diseases.

Acute liver insufficiency is a rare complication of anorexia nervosa. The mechanisms for this complication are unclear. The aim of this study was to describe patient characteristics and clarify the mechanisms involved.Liver specimens from 12 patients (median age, 24 years; median body mass index, 11.3 kg/m(2)), with a prothrombin index50% and/or an International Normalized Ratio1.7 and anorexia nervosa as the only cause for acute liver injury were analyzed. A detailed pathologic examination was performed, including under electron microscopy.Liver cell glycogen depletion was a constant finding. There was a contrast between the increase in serum alanine aminotransferase (56 times normal on average; 1,904 IU/L) and the absence of significant hepatocyte necrosis on histology. Centrilobular changes (trabecular atrophy and/or sinusoidal fibrosis) were observed in 6 patients. There were rare or no (5%) terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes, suggesting that apoptosis was not the primary mechanism. Hepatocytes from 4 patients showed numerous autophagosomes, a morphologic hallmark of autophagy, on electron microscopy. In contrast, the mitochondria, endoplasmic reticulum, and nuclei were normal in most cells. These features were absent in 11 control patients. The outcome was favorable in all patients, with a rapid return to normal liver function.Anorexia nervosa with extremely poor nutritional status should be added to the list of conditions causing acute liver insufficiency. Our findings show that starvation-induced autophagy in the human liver may be involved in liver cell death during anorexia nervosa, even though other mechanisms of liver cell damage could also play a role.

Although it is often functional at presentation, acute renal failure has a poor prognosis in patients with cirrhosis. The role of inflammation, a key event in the outcome of cirrhosis, has never been studied in this setting. We aimed to investigate the predictive factors of mortality in patients with cirrhosis and acute functional renal failure, specifically in relation to inflammatory events. One hundred consecutive patients with cirrhosis from 5 French hospitals were prospectively included at the day of onset of acute renal failure. Medical history, treatments, and procedures during the month before inclusion were recorded. Physical examination, blood and urinary chemistries, and renal ultrasound examination were performed. The presence of systemic inflammatory response syndrome (SIRS), infection, and sepsis was assessed. The primary outcome was in-hospital mortality. The mechanism of renal failure was functional in 83 patients. Causes of renal failure were hypovolemia (34%), hepatorenal syndrome without ongoing infection (17%), hepatorenal syndrome with ongoing infection (16%), nephrotoxicity (2%), and multifactorial (31%). SIRS was observed in 41% of patients, 56% of them with infection. In-hospital mortality was 68% in patients with SIRS and 33% in patients without (P = 0.001). In multivariate analysis, only model for end-stage liver disease score and presence of SIRS, but not infection, remained associated with a poor outcome. Conclusion: The presence of SIRS, with or without infection, is a major independent prognostic factor in patients with cirrhosis and acute functional renal failure. This suggests that preventing and treating SIRS could decrease mortality in patients with cirrhosis and acute renal failure. (HEPATOLOGY 2007.)

4079 Background: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC) with a yearly incidence ranging from 1 to 8%. EASL and AASLD guidelines recommend systematic ...

Hepatitis C virus-related end-stage liver disease, alone or in combination with alcohol, has become the leading indication for liver transplantation in most transplant programs accounting for approximately half of transplants performed in European centers. Hepatitis C virus infection recurs virtually in every post-transplant patient. The natural history of hepatitis C after liver transplantation is variable. Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10% of the patients with recurrent disease will die or require re-transplantation within 5 years post-transplantation. Several factors, including those related to the virus, the host, the environment and the donor, are probably implicated in the outcome. The immune status represents the main significant variable in influencing disease severity in hepatitis C virus-infected patients; with higher HCV viral load and the significant association described between the degree of immunosuppression and disease severity. Interventions to prevent, improve, or halt the recurrence of hepatitis C virus infection have been evaluated by multiple small studies worldwide with similar overall rates of virological clearance of approximately 9-30%. Current consensus recommends combination therapy with pegylated interferon and ribavirin for those patients with histological recurrence of hepatitis C virus infection and fibrosis. Therapy is adjusted to tolerance and rescued with granulocyte colony-stimulating factor and erythropoietin for bone marrow suppression. In this article we present a comprehensive review of post-transplant hepatitis C virus infection; in particular fibrosis progression and the major challenges according to treatment.

Amanita phalloides poisoning is an uncommon cause of acute liver failure with an especially rapid course. The aim of this study was to re-assess transplantation criteria in patients with mushroom poisoning.Twenty-seven patients admitted for Amanita phalloides poisoning were studied. Previously reported transplantation criteria, including the recent Ganzert's criteria, were tested retrospectively.The rate of fatal intoxication (death and/or transplantation) was 8/27 (30%). An interval between ingestion and diarrhea8h was a very early predictor of a fatal outcome (accuracy of 78%). Later on, non-paracetamol and paracetamol King's College criteria were superior to Clichy's and Ganzert's criteria (accuracy of 100% compared to 85% and 85%, respectively). Encephalopathy and renal insufficiency were not constant in the fatal intoxication group. Prothrombin index below 10% 4 days or more after ingestion had a 100% accuracy for predicting a fatal outcome.Liver transplantation should be strongly considered in patients with an interval between ingestion and diarrhea8h. Encephalopathy should not be an absolute prerequisite for deciding transplantation. From day 4 after ingestion, prothrombin index lower than 10% ( approximately INR of 6) alone is a reliable tool for deciding emergency transplantation.

Living donors represent a recognized alternative for facilitating the access to transplantation in a period of organ shortage. However, which candidates should be preferentially considered for living-donor liver transplantation (LDLT) is debated. The aim of this study was to create statistical models to determine which strategies of selection for LDLT provide the most efficient contribution. The study included 331 patients listed for deceased-donor transplantation (DDLT) and 128 transplanted with living donors. Statistical models predicting the events following listing were created and combined in a multistate model allowing the testing of different strategies of selection for LDLT and to compare their results. Taking 3-yr survival after listing as the principal end-point, selecting the 20% patients at highest risk of death on the waiting list gave better results than selecting the 20% patients at lowest risk of death after LDLT (70% vs. 64%, respectively). These strategies resulted in waiting list mortality rates of 17% and 8%, respectively. One-year survival after LDLT was lower in high-risk patients (85%) than in low-risk patients (91%). However, the 1-yr survival benefit derived from LDLT was 75% in high-risk patients while it was nil in low-risk patients. In conclusion, LDLT is more effective for overcoming the consequences of organ shortage when performed in patients at high risk of death on the waiting list. On an individual basis, the sickest patients are those who derive the most important benefit from LDLT. This study provides incentives for considering LDLT in high-risk patients.

Background. One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. Methods. The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. Results. In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. Conclusions. In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.

297 Background: We aim to evaluate in our institution the incidence of de novo malignancies following orthotopic liver transplantation (OLT) and their impact the prognosis of patients (pts). Methods: Pts treated with OLT from August 1991 To March 2009 were considered in this analysis. All pts data had been prospectively recorded in the database of French “Bio-medecine Agence”. Pts were considered for this analysis only if they survived at least 3-months after. Occurrence of de novo malignancies we analyzed and additional data (including immunosuppressive profile, type of cancer, potential independent risk factors of cancers, prognosis and the influence of immunosuppression protocols or risk factors on occurrence of cancers) were collected in patients who developed secondary cancers. Results: A total of 833 patients who underwent OLT were considered for this analysis. With a median follow-up of 7.9 years, 72 pts developed 92 de novo malignancies. The overall incidence of cancers in our population was 10.4% occurring with a median time of 6.1 years following OLT. Sixteen pts developed 2 different types of cancer and 2 pts had more than 3 tumor types. Before 12/1998, immunosuppression was primarily based on cyclosporine, steroids and/or azathiopirine, and since 01/1999 was switched to tacrolimus. Incidence of cancers regarding these two periods is summarized in the table. Before 1998, only 3 pts (17.6%) with secondary cancer had prior history of alcoholism and/or smoking compared to 27 pts (50%) after 1999. Thirty one deaths were observed and the median overall survival (OS) after the time of diagnosis of secondary malignancy was 5.62 years. Conclusions: The risk of de novo cancer after OLT is similar to reported series. History of smoking and alcohol use, increase the incidence of de novo malignancies especially head and neck and lung cancers however, immunosuppression type may not interfere with this risk. [Table: see text]

W72 for the three renal groups were 1.1, 1.2 and 1.4mg/dL and median change from baseline was −0.10, 0, and −0.20, respectively. Four patients with mild renal impairment at baseline had a confirmed creatinine clearance

Introduction L’hydrothorax hepatique est une complication rare de la cirrhose dont la prise en charge therapeutique est difficile. Il est generalement admis que la transplantation hepatique est le meilleur traitement dans cette situation. Le but de ce travail est d’etudier les repercussions de l’hydrothorax hepatique pre-operatoire sur l’evolution post-transplantation de foie. Patients et Methodes Nous avons etudies retrospectivement 273 patients adultes qui ont beneficies d’une transplantation hepatique entre janvier 2002 et decembre 2005. Onze patients presentant un hydrothorax hepatique ont ete identifies (groupe 1). Six necessitaient des thoracocentheses repetees. Les donnees demographiques, les complications post-operatoires et la survie de ces patients ont ete comparees avec deux groupes controles de 11 patients, apparies pour l’âge, le sexe, l’annee de transplantation et la severite de la cirrhose. Le groupe 2 incluait des patients avec une ascite tendue sans hydrothorax et le groupe trois des patients sans ascites. Resultats Les caracteristiques pre-transplantations n’etaient pas differentes entre les groupes, exceptee la presence d’ascite. Il n’y avait pas de differences dans la duree de la ventilation mecanique post-operatoire, et la duree de sejour aux Soins Intensifs. Aucune difference n’etait notee dans la frequence d’infections post-operatoires ou de deces post interventionnel. Par contre, la cause de deces post-operatoire etait differente : 3 patients du groupe 1 etaient morts de bronchopneumonies infectieuses alors qu’aucun deces de cette cause n’etait releves dans les autres groupes. Conclusion La transplantation hepatique est une bonne option therapeutique chez les patients cirrhotiques presentant un hydrothorax hepatique. Cet hydrothorax n’implique pas plus de complications post-operatoires. L’evolution d’une bronchopneumonie post-operatoire semble moins bonne que chez les patients sans hydrothorax hepatique.

Intoxication with the mushroom Amanita phalloides (AP) is a rare cause of acute liver failure, sometimes requiring emergency liver transplantation (LT). The current criteria for LT seem poorly applicable because of the especially rapid course of liver failure. The aims of this study were to identify risk factors after intoxication with AP and to propose criteria for emergency LT. Twenty five patients admitted for intoxication with AP were studied (12 males and 13 females, mean age 49 years). Six out of these 25 patients developed acute liver failure. Three were transplanted (only one survived); one died before transplantation and 2, who were rejected for LT, died. Predictive factors for a poor outcome (death or LT) were female gender (7/7 vs 5/18, p=0.001), a short interval between ingestion and diarrhea (7h vs 12h, p=0.001), prolonged prothrombin time (p=0.0003), serum transaminases rebound (reflecting an initial collapsus with hepatic ischemia followed by AP toxicity, 4/7 vs 1/18, p=0.01) and encephalopathy (6/7 vs 1/18, p

Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis. Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of patients with advanced alcoholic cirrhosis, similar to those found in primary IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N -glycosylation, not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA deposits were associated with CD71 overexpression in mesangial areas, suggesting that CD71 might be involved in deposit formation. Although the IgA1 found in alcoholic cirrhosis bound more extensively to human mesangial cells than control IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation. Thus, abnormally glycosylated IgA1 and soluble CD89–IgA and IgA–IgG complexes, features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common mechanisms appear to be shared by diseases of distinct origins, indicating that common environmental factors may influence the development of IgAN.