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The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed.All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching.Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002).ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.

International audience; BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

After liver transplantation (LT), the role of preformed donor-specific anti-human leukocyte antigen antibodies (pDSAs) remains incompletely understood. We conducted a retrospective, case-control analysis to determine the impact of pDSAs after LT in 3 French transplant centers (Bordeaux, Lyon, and Toulouse). Among the 1788 LTs performed during the study period, 142 (7.9%) had at least 1 pDSA. The patient survival rate was not different between patients who received an LT with pDSAs and the matched-control group. A liver biopsy was performed 1 year after transplantation in 87 recipients. The metavir fibrosis score did not differ between both groups (1 ± 0.8 versus 0 ± 0.8; P = 0.80). However, undergoing a retransplantation (hazard ratio [HR] = 2.6, 95% confidence interval [CI], 1.02-6.77; P = 0.05) and receiving induction therapy with polyclonal antibodies (HR = 2.5; 95% CI, 1.33-4.74; P = 0.01) were associated with a higher risk of mortality. Nonetheless, high mean fluorescence intensity (MFI) donor-specific antibodies (ie, >10,000 with One Lambda assay or >5000 with Immucor assay) were associated with an increased risk of acute rejection (HR = 2.0; 95% CI, 1.12-3.49; P = 0.02). Acute antibody-mediated rejection was diagnosed in 10 patients: 8 recipients were alive 34 (1-125) months after rejection. The use of polyclonal antibodies or rituximab as an induction therapy did not reduce the risk of acute rejection, but it increased the risk of infectious complications. In conclusion, high MFI pDSAs increase the risk of graft rejection after LT, but they do not reduce medium-term and longterm patient survival. The use of a T or B cell-depleting agent did not reduce the risk of acute rejection.

Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context.This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied.Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance.The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT10%, without any signs of elevation after a median period of 3 days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT.Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%-20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6-18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels

Patients with nonresectable liver metastases from colorectal cancer have few therapeutic options and a dismal prognosis. Although liver transplantation for this indication has historically a poor reputation, recent advances in the field of chemotherapy and immunosuppression have paved the way to revisit the concept. New data have shown promising results that need to be validated in several ongoing clinical trials. Since liver grafts represent a scarce resource, several new tools are being explored to expand the donor pool for this indication. The purpose of this review is to present all current available data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.

Prognostic models of liver transplantation (LT) for hepatocellular carcinoma (HCC) mainly derive from LT cohorts with numerous hepatitis C virus (HCV) patients. The AFP model, which is currently used in France to select LT candidates, was derived from a cohort of LT performed between 1988 and 2001, including a majority of HCV-positive recipients. The emergence of new direct-acting antiviral therapies and subsequent decrease of HCV incidence may change the generalizability of such models. We performed an external validation of the AFP model in a cohort of recipients transplanted between 2005 and 2018. Although multivariable analysis identified all three model's factors (AFP level, largest tumor size, number of nodules) as predictors of tumor recurrence, the AFP model showed poor discrimination and calibration in the present cohort. This poor performance could be related to significant differences between the derivation and the present cohort in terms of etiology, severity of underlying liver disease, tumor burden and differentiation, and use of neoadjuvant treatments. The present findings suggest that the decline of HCV-induced HCC among LT candidates may compromise the generalizability of the AFP model in more recent LT cohorts. Further studies are required for updating or building more robust prognostic models.

International audience; Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR

Background: Hereditary transthyretin amyloidosis (ATTR) is a multisystemic disease involving mainly the peripheral nervous system and the heart. Liver transplantation (LT) is the reference treatment for ATTR neuropathy and preoperative detection of high risk patients is crucial. We aimed to document the causes of death of ATTR patients after LT, their temporal trends, and to evaluate whether the available preoperative tools that predict the risk of death after LT for hereditary ATTR amyloidosis matched with these trends. Methods: A retrospective longitudinal cohort study was performed on 215 consecutive ATTR patients who underwent LT between January 1993 and January 2011. Each patient’s death cause and timing were classified. Results: Over a median follow up of 5.9 years, 84 patients died. The rate of death was higher in the first year following LT than thereafter (13.0 vs. 4.3 ± 1.8%/year; p = .004). Cardiac events ranked as the leading cause of death (C: 38%), followed by infections (I: 24%), graft complications (G: 17%), end stage amyloidosis, stroke and others (ASO: 7% each). Deaths due to graft complications and infections (GI) occurred earlier than those due to end stage amyloidosis and stroke. Death prediction was less accurate for GI-related mortality than for other causes, which blunted the accuracy of the early-term risk prediction scores. Conclusions In ATTR amyloidosis, cardiac events were the leading cause of death after liver transplantation. Close preoperative evaluation allowed for accurate mid-term prediction of mortality, but the high rate of graft complications and infections blunted the early-term risk prediction.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare severe adverse drug-induced reaction with multiorgan involvement. The outcome and prediction of those patients who develop severe acute liver injury (sALI) or acute liver failure (ALF) remain little known.A multicenter retrospective study of patients admitted with a diagnosis of DRESS-related sALI or ALF. Histological review was performed on liver core biopsies from native livers.Sixteen patients (11 women, 5 men; mean age, 39±17.2 years) were classified as having definite (n=13) or probable (n=3) DRESS. At admission, 3 patients had hepatic encephalopathy; median levels of prothrombin time, INR, and total bilirubin were, respectively, 33% (Q1-Q3, 21-41), 2.74 (1.98-4.50), and 94 μmol/L (Q1-Q3, 39.5-243.5). Nine patients received corticosteroid therapy. Overall, 9 patients improved spontaneously and 7 worsened (liver transplantation [LT] (n=5), deceased (n=2)). Transplantation-free and post-LT survival was 56% and 60%, respectively. After LT, DRESS recurrence was observed in 3 of 5 patients. Systemic corticosteroid therapy was not significantly associated with a clinical improvement. In the multivariate analysis, factor V level less than 40% at day 0 and factor V levels of 40% or greater at admission but decreasing at day 2 were associated with worse outcome. Pathological findings (n=7) revealed atypical lymphoid infiltrates, Kupffer cell hyperplasia with erythrophagocytosis, and an inconstant presence of eosinophils.The spontaneous prognosis of patients with sALI/ALF due to DRESS is poor and was not improved by corticosteroid therapy. Histology is helpful to establish diagnosis. Dynamic variables regarding factor V values are predictive of a poor outcome.

Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm2 (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm2 (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P

Summary Transition describes a progressive and highly coordinated process encompassing the transfer of a young patient from paediatric care to the adult-care system. Transfer of medical care for an adolescent to adult services is a complex and challenging task requiring close collaboration of both the paediatric and adult-care providers. It must take into account the medical, psychosocial and educational needs of the young adult. The Transition Working Group of the French Network for Rare Liver Diseases (FILFOIE) proposes recommendations and tools designed to optimise the transition process of adolescents and young adults with chronic liver disease from child-based to adult-based healthcare services, focusing on three key time points: preparation before the transfer, the transfer process to the adult service, and finally reception and follow-up within the adult-care service.

This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5-year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P = 0.01). In the LT group, 5-year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2-5 cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population.

International audience; Background: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC.Patients and methods: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013.Results: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P

Background A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. Methods Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). Results The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log 10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm 3 (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. Conclusions SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Background Few studies have investigated infections in human immunodeficiency virus (HIV)-infected liver transplant patients. The aim of this study was to describe the prevalence, time of onset, mortality of infectious complications, other than hepatitis C virus (HCV), and to identify risk factors for their development in a large single-center cohort of HIV-infected liver transplant patients. Methods We studied 109 consecutive HIV-infected patients who underwent liver transplantation (LT) between 1999 and 2010 and followed until December 2012. Results The median age was 44 years (interquartile range [IQR] 41–49), 82.6% were male, and the median follow-up was 45.7 months (IQR 14–65). The major indications for LT were HCV cirrhosis (61%) and hepatocellular carcinoma (19%). Forty patients (37%) developed at least 1 infection during the first year after LT. Twenty-eight (26%) patients had an episode of bacteremia. Five (4.6%) patients developed a cytomegalovirus infection. Fungal infections occurred in 5 (4.5%) patients. Four (3.6%) patients developed an HIV-related opportunistic infection. A total of 43 (39.4%) patients died during follow-up. Mortality related to infection occurred in 9 (7%) cases, and 20 (42.5%) patients died because of HCV recurrence. No patients died from opportunistic infections. Model for end-stage liver disease (MELD) score >17 was associated with a 2-fold higher risk (hazard ratio 1.96; 95% confidence interval 1.01–3.80) of developing infectious complications. Conclusions Infections are not a major cause of mortality after LT in HIV patients and opportunistic infections of acquired immunodeficiency syndrome are infrequent. A MELD score >17 increased the risk of developing post-LT infectious complications. Recurrence of HCV infection remains a major cause of mortality.

OBJECTIVE Severe hepatitis C virus (HCV) recurrence affects post-transplant survival in HIV/HCV co-infected patients. This article describes the results of triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co-infected patients following liver transplantation. METHODS All patients had severe HCV recurrence [fibrosis stage ≥F2 or acute hepatitis ≥A2 (n = 5) or fibrosing cholestatic hepatitis (n = 2)] associated with genotype 1a (n = 4) or 1b (n = 3). Patients were treated with Peg-interferon/ribavirin and boceprevir (n = 2) or telaprevir (n = 5) immediately (n = 3) or after a 4-week lead-in phase (n = 4). Immunosuppression included either cyclosporine (n = 5) or tacrolimus (n = 2). Prior to introducing telaprevir, combined antiretroviral therapy was switched in one patient to prevent drug-drug interactions. RESULTS At 24 weeks after the end of treatment, sustained virological response was observed in 60% (3/5) of the patients treated with telaprevir; no responders were observed in the boceprevir group. Triple anti-HCV therapy was prematurely discontinued in six patients [treatment failure (n = 2), infection (n = 2), acute rejection (n = 1) and myocardial infarction (n = 1)]. Anaemia occurred in all patients, requiring erythropoietin, ribavirin dose reduction and red blood cell transfusions in five patients.Average cyclosporine doses were reduced by 50-84% after telaprevir initiation and by 33% after boceprevir initiation. Tacrolimus doses were reduced by 95% with telaprevir. CONCLUSION Our data suggest that in HIV/HCV co-infected patients, triple anti-HCV therapy with telaprevir greatly improved efficacy despite poor tolerability. Significant decreases in cyclosporine or tacrolimus doses are necessary prior to introduction of boceprevir or telaprevir. Close monitoring is essential to prevent drug-drug interactions among antiretroviral therapy, immunosuppressive agents and anti-HCV therapy.

Introduction The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. Methods All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. Results Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. Conclusions In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

Background & Aims: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. Methods: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). Results: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients’ inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5–95.4), 80.3% (95% CI 76.9–83.9), and 3.2% (95% CI 1.6–4.8) respectively. Conclusion: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. Lay summary: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Methods Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. Results One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506–0.907) and 0.71 (95% confidence interval, 0.646–0.917), respectively. Liver stiffness measurement ≥22 kPa had 42.9% sensitivity and 92.6% specificity and hepatic venous pressure gradient ≥10 mm Hg had 28.6% sensitivity and 96.3% specificity. Conclusion In selected patients undergoing liver resection for hepatocellular carcinoma, transient elastography is an easy and effective test to predict persistent hepatic decompensation preoperatively.

Transthyretin-related amyloidosis (ATTR) is an autosomal dominant disease affecting the peripheral and autonomic nervous system, heart, eyes and kidneys. It is the most disabling hereditary polyneuropathy in adults. The French National Reference centre for this disease was accredited in 2005 with 10 lines of action. One of them is to inform and educate patients about their disease to improve their care and reduce morbidities. We thus decided to elaborate a therapeutic patient education (TPE) programme, starting with patients' needs assessment.A qualitative research study was conducted with one-to-one semi-structured interviews of selected individuals. Recorded interviews were analysed to identify the skills that patients need to acquire. A TPE programme was elaborated on the basis of these findings.Seven patients, one asymptomatic carrier and two healthy spouses were interviewed. Analysis of the interviews showed that interviewees had a good knowledge of the disease and its symptoms but they had difficulties explaining the disease mechanism and did not have an adequate knowledge of the available treatment options, although they knew that liver transplant might halt progression of the disease. ATTR amyloidosis appeared to have a major negative impact on the patient's physical and mental well-being. Patients feared loss of autonomy and having to require assistance from their relatives and spouses. All interviewees were keen to participate in a TPE programme. Based on this needs assessment, we identified seven skills that patients need to acquire and several pedagogical goals to be achieved during the education programme. An interdisciplinary team then elaborated a complete TPE programme.Elaboration of a TPE programme for ATTR amyloidosis required to obtain useful information from the patients themselves, and their relatives, concerning their perception of their disease. This needs' assessment constituted the basis for designing the first TPE programme, to our knowledge, for ATTR amyloidosis. After translation, this programme could be applied in other EU countries and worldwide for this rare disease.

Background & Aims Hepatitis E virus (HEV) infection is a known cause of acute-on-chronic liver failure in developing countries, but its implication in Western countries remains unknown. HEV burden in the setting of severe acute alcoholic hepatitis (AAH) was assessed. Methods Patients admitted for severe AAH from 2007 to 2013, with available sera and histologically proven AAH, were included and managed according to current European guidelines. At admission, clinical and biological characteristics were collected; HEV serology and RNA detection were retrospectively performed. Results Eighty-four patients were included. Mean age was 50.8 ± 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 ± 11.4 and 73.3 ± 37. Liver biopsy showed mild, moderate and severe hepatitis in 25 (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to 61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille score: 0.78 ± 0.21). During hospitalization, 24 patients (28.6%) died and 11 (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV infection and 21 (25%) markers of past HEV infection. Patient with acute infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids were given to two patients without any response. The third patient died. None were transplanted. Conclusions A substantial proportion of patients with severe AAH had markers of acute HEV infection, with similar clinical presentation and outcomes. Larger studies are needed to evaluate HEV impact on AAH management, resistance to steroids, and outcome.

International audience; BACKGROUND & AIMS: Liver transplantation (LT) for the most severely ill patients with cirrhosis, with multiple organ dysfunction (accurately assessed by the acute-on-chronic liver failure [ACLF] classification) remains controversial. We aimed to report the results of LT in patients with ACLF grade 3 and to compare these patients to non-transplanted patients with cirrhosis and multiple organ dysfunction as well as to patients transplanted with lower ACLF grade. METHODS: All patients with ACLF-3 transplanted in three liver intensive care units (ICUs) were retrospectively included. Each patient with ACLF-3 was matched to a) non-transplanted patients hospitalized in the ICU with multiple organ dysfunction, or b) control patients transplanted with each of the lower ACLF grades (three groups). RESULTS: Seventy-three patients were included. These severely ill patients were transplanted following management to stabilize their condition with a median of nine days after admission (progression of mean organ failure from 4.03 to 3.67, p=0.009). One-year survival of transplanted patients with ACLF-3 was higher than that of non-transplanted controls: 83.9 vs. 7.9%, p\textless0.0001. This high survival rate was not different from that of matched control patients with no ACLF (90%), ACLF-1 (82.3%) or ACLF-2 (86.2%). However, a higher rate of complications was observed (100 vs. 51.2 vs. 76.5 vs. 74.3%, respectively), with a longer hospital stay. The notion of a "transplantation window" is discussed. CONCLUSIONS: LT strongly influences the survival of patients with cirrhosis and ACLF-3 with a 1-year survival similar to that of patients with a lower grade of ACLF. A rapid decision-making process is needed because of the short "transplantation window" suggesting that patients with ACLF-3 should be rapidly referred to a specific liver ICU. Lay summary: Liver transplantation improves survival of patients with very severe cirrhosis. These patients must be carefully monitored and managed in a specialized unit. The decision to transplant a patient must be quick to avoid a high risk of mortality.

Familial transthyretin amyloidosis (ATTR) is a rare, life-threatening, autosomal dominant disease involving mainly the heart and the peripheral nervous system due to a point mutation of the transthyretin ( TTR ) gene. By removing the main source of the mutated TTR , liver transplantation (LT) has

International audience; OBJECTIVES This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver transplantation (LT). BACKGROUND mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. METHODS In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability, (123)-meta-iodobenzylguanidine heart/mediastinum ((123)-MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). RESULTS Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score, (123)-MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The (123)-MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either (123)-MIBG H/M ratio (SMIBG) or HRRA (S-atropine). AUC of S-MIBG and S-atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S-MIBG, S-atropine, and a reference clinical model (AUC: 0.785) were similar. CONCLUSIONS Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia, (123)-MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome. (C) 2016 by the American College of Cardiology Foundation.

We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.

BACKGROUND In patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV), evolution toward cirrhosis and its complications is more rapid and severe than in patients infected with HBV alone. The outcome of liver transplantation in HBV-HIV-coinfected patients is poorly understood in terms of survival rate, HBV reactivation and mitochondrial toxicity on the liver graft. PATIENTS AND METHODS Between November 2002 and June 2007, 13 HIV-positive patients underwent liver transplantation because of end-stage liver disease due to HBV with or without coinfection with hepatitis D or C virus. These patients were prospectively followed for an average of 32 +/- 5.2 months (range 10-63 months). RESULTS All patients were alive at the end of the follow-up period and had normal liver function. Their HBV viral load was undetectable, no cccDNA was found in the liver graft and HIV infection was nonprogressive under antiretroviral therapy. Moreover, no mitochondrial toxicity was noted in the liver graft, as assessed by the spectrophotometric analysis of respiratory chain activities and by quantifying the mitochondrial DNA copy number. CONCLUSION HBV-HIV-coinfected patients can successfully undergo liver transplantation with excellent results in terms of survival, control of HBV replication after transplantation and mitochondrial toxicity.

International audience; In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non–paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance ≥ 60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level \textless 200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level \textgreater 20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level \textless 200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non–paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance. Liver Transpl 21:512-523, 2015. © 2015 AASLD.

Drug-induced hepatotoxicity is an important cause of hepatocellular injury. Non-nucleoside retroviral transcriptase inhibitors are known to cause hepatotoxicity. We describe a detailed case of fulminant hepatitis induced by nevirapine (Viramune) and treated by liver transplantation.

We report, for the first time, the outcome of anti-hepatitis C virus (HCV) triple therapy with telaprevir in an HIV/HCV co-infected transplanted patient. After liver transplantation, the patient experienced a severe HCV recurrence with fibrosing cholestatic hepatitis, and anti-HCV therapy with pegylated interferon alpha 2a, ribavirin and telaprevir was initiated. A sustained virological response was achieved after 48 weeks of anti-HCV therapy. Drug-drug interactions between antiretroviral therapy, immunosuppressive agents and anti-HCV therapy could be managed.

Domino liver transplantation (DLT) has become an accepted procedure designed to address problems with organ limited supply. However, cases of acquired amyloid neuropathy are increasingly being recognized following this procedure. Until now, only one patient had undergone liver retransplantation and follow-up findings were not reported. We describe the case of a 72-year-old patient with partial recovery from acquired amyloid neuropathy following retransplantation with a deceased donor 7 years after DLT performed for end-stage liver disease. His clinical and paraclinical improvement is described, and the impact of this case on the indication for a domino procedure and the challenges linked to retransplantation are discussed.

Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of β-erythropoietin ( n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log 10 IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT.

Domino transplantation using the liver (DLT) from patient with familial amyloid polyneuropathy (FAP) has been developed to alleviate the graft shortage. We herein studied 91 patients who ...

Background & Aims Most liver transplant centres have discontinued the practice of protocol liver biopsies (LB), mainly because of the perceived lack of therapeutic benefit. This study aimed to examine the usefulness of 20-year LBs. Methods Ten, 15, and 20-year protocol LBs from 147 patients surviving for >20years were reviewed. Twenty-year biopsy findings were correlated with clinical data. Results Twenty-year-biopsy patients (N=91) and 20-year-non-biopsy patients (N=56) were similar in terms of transplant data, adverse events, and liver function tests (LFTs). Twenty-year LBs revealed a 90% prevalence of abnormalities, among which viral chronic hepatitis (VCH) was the most common (46%). Between 15 and 20years, hepatic structural abnormalities were the only disorder to increase ( p =0.008). An individual progression of abnormalities occurred in 56% of patients. At 20years, the negative and positive predictive values (PV) of LFTs with respect to histological abnormalities were 95% and 18%, respectively; in VCH, Fibrotest and transient elastography displayed poor discriminative ability for fibrosis (80% and 81% discordance, respectively), but were satisfactory regarding significant fibrosis (negative PV of 77.7% and 80%, respectively). A decrease in immunosuppression was less frequent (14/91 vs . 20/56, p =0.008) while an increase was more common (15/91 vs . 2/56, p =0.017) in 20-year-biopsy patients than in non-biopsy patients. Antiviral therapy was administered in seven of the 20-year biopsy patients, but in none of the non-biopsy patients ( p =0.04). Conclusions Twenty-year LBs provided important histological information on graft function that was available to a limited degree from LFTs and non-invasive markers. They exerted an impact on immunosuppressive and antiviral therapies.

The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 ± 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients.

ABO-incompatible (ABO-I) liver transplantation has been performed essentially in patients with acute liver failure awaiting an urgent liver transplantation. Early results with ABO-I liver transplantation were disappointing with a very low graft survival rate (20-50%). The main risk is the occurrence of severe humoral and cellular rejection, vascular thrombosis, and biliary complications. In order to avoid humoral rejection and improve graft survival, total plasma exchange in combination with an intense immunosuppressive regimen has been proposed to decrease hemagglutinin titers in ABO-I liver grafts. In some centers, this regimen was associated with splenectomy, phototherapy, and portal or arterial intrahepatic infusion therapy; however, as these patients are at high risk of sepsis, a selective approach using antigen-specific immunoadsorption with immunoadsorbent columns has been successfully proposed for ABO-I living donor kidney transplantation. Few cases have been reported following liver transplantation. We report our recent experience with three adult patients (two patients with acute liver failure, and one with severe cirrhosis and hepatic encephalopathy) transplanted in an emergency situation with an ABO-I liver graft and managed with the use of GlycoSorb ABO immunoadsorbent columns and a quadruple immunosuppressive regimen with preservation of the spleen. Eight sessions were performed in the three patients. Antigen-specific immunoadsorption greatly lowered the anti-A hemagglutinin titers. None of the three patients developed acute humoral or cellular rejection. Two patients are alive at 1.5 and 3 years follow-up with a normally functioning graft. The third patient died with a functioning graft, one month after the transplantation, from septic complications.

The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV)-coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir-exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm3. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence.

Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n = 29, pegylated IFN [pegIFN], n = 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stageor =3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Fibrosis stageor =3 was associated with a high rate of liver failure, arguing for an early introduction of antiviral therapy.

Sofosbuvir and daclatasvir are direct-acting antiviral drugs used to treat chronic hepatitis C virus infection. In 2015, the Food and Drug Administration and European Medical Agency warned that bradycardia could occur when amiodarone was administered in combination with sofosbuvir, but no case reports had been published. We report extreme bradycardia within 2 hrs after intake of sofosbuvir and daclatasvir by 2 patients receiving amiodarone. The first patient had a cardiac asystole 30 min after receiving sofosbuvir and daclatasvir. Amiodarone, sofosbuvir, and daclatasvir treatment were stopped; after 10 days, the cardiac evaluation was normal and patient was discharged. The second patient was taking amiodarone and propranolol; 2 hrs after receiving sofosbuvir and daclatasvir, he had an extreme sinus node dysfunction (heart rate of 27beats/min). Amiodarone and propranolol were stopped, but the patient continued receiving sofosbuvir and daclatasvir for 3 days and sinus bradycardia was recorded each day, 2 hrs after intake of these drugs. When he stopped taking the drugs, no bradycardia was observed. Administration of sofosbuvir and daclatasvir on day 13 induced bradycardia 2 hrs after intake. However, no bradycardia occurred following a rechallenge 8 weeks after the patient stopped taking amiodarone. These observations indicate that patients treated with amiodarone should be continuously monitored within the first 48 hrs following the initiation of sofosbuvir and daclatasvir.

Background and Aims: The association of liver steatosis with a number of common metabolic conditions has been suggested. The aim of the present study was to evaluate the clinical features of subjects with different severities of steatosis. Methods: The present study was performed in 282 consecutive patients with ‘bright liver’ at ultrasonography and in 58 subjects without steatosis. They had no history of alcohol abuse and negative tests for the presence of hepatitis B and C virus. Patients underwent clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. Steatosis was graded as absent, mild, moderate and severe. Results: A progressive increase in the prevalence of obesity (P

Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p Conclusion Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis. Trial registration: ClinicalTrials.gov registry number: NCT01953458.

International audience; No abstract available

International audience; Despite universal health coverage in France, migrants face specific socioeconomic barriers that increase the likelihood of a suboptimal cascade of care for chronic hepatitis C virus (HCV) infection and impaired treatment effectiveness in this sub-population. We selected data collected from 2012 to 2018 from the ANRS CO22 HEPATHER prospective cohort study for chronic HCV participants with available data on treatment failure (defined as the presence of a detectable HCV-RNA load 12 weeks after their first DAA treatment ended). We performed multivariable Poisson regression models to test whether treatment failure rates differed significantly between HCV-infected migrants and non-migrants receiving DAA in France (cross-sectional analysis), while taking into account the former's world region of birth and other potential social vulnerability factors. Among the study population's 7,879 patients, 5,829 (74%) were non-migrants and 2,050 (26%) migrants. Median [interquartile range] age was 57 [51-65] years, 4433 (56%) were men and 369 (5%) of the entire study population had treatment failure. After multivariable adjustment, only migrants from Central Asia were at higher risk of treatment failure than non-migrants (aIRR = 2.83; 95% CI [1.72, 4.65]). Results from this large-scale study performed in France suggest a higher risk of DAA treatment failure in migrants from Central Asia than in non-migrants and confirm the overall low treatment failure rate in chronic HCV patients treated with DAA (whether migrants or not). Simplified models of care taking into account language and cultural barriers are needed to improve DAA effectiveness in migrants from Central Asia.

International audience; Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients’ clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P