Search

Hepatitis E virus (HEV) is an agent responsible for waterborne acute hepatitis in tropical and subtropical areas. Epidemiological and molecular data indicate zoonotic transmission of HEV in industrialized countries. Genotypes 1 and 2 HEV are found only in humans. By contrast, genotypes 3 and 4 HEV have been characterized both in humans and several animal species (pigs, wild-boars, deers and rodents). Hepatitis E can evolve towards chronicity and rapidly progressive cirrhosis in immunosuppressed patients: organ transplant recipients, patients with hematological diseases and immunodeficiency virus type 1 infected patients with low CD4 cell count. So far, genotype 3 has been the only HEV genotype described in chronic hepatitis E. Host factors and the level of immunosuppression are major factors associated with virus persistence. The reduction of immunosuppressive therapy and treatment with alphainterferon and/or ribavirin are considered as promising therapeutic options.

Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.

573 Background: CABO is approved in second (2L) or third line (3L) systemic therapy for pts with advanced HCC after SOR failure, based on results of the CELESTIAL phase 3. CLERANCE was designed to evaluate safety and efficacy of CABO in pts with HCC in real-world practice in a French population. Methods: This prospective, French multicentre (n=17), interventional study aims to recruit 110 pts with unresectable HCC when a decision of CABO treatment was made in 2L or 3L after prior sorafenib (SOR) failure, according to the French health authority approved label. The primary endpoint is the incidence of treatment-related adverse events (TRAE) of grade > 2 (NCI-CTCAE v5) by a central review committee. Secondary endpoints include overall survival (OS), objective response rate (ORR) (RECIST v1.1 per investigator assessed), progression-free survival (PFS), time to progression (TTP) and profiles of CABO administration. Results: Of 110 pts enrolled, the final analysis focused on the 99 pts who starting CABO (11 pts withdrawn due to screen failure) and followed up to 12 mo (data cut-off: November 8, 2021). Pts were mainly males (89%), 69 years median age (range 24-85), Child-Pugh A (94.9%) / B7 (5.1%), and ALBI score-1 (33%), 2 (60%), 3 (5%), not evaluated (NE) (2%). About 59% pts received CABO in 2L after SOR, whereas 41% were in 3L after SOR and another line (TKI or IO). SOR was discontinued due to tumor progression (68%) or intolerance (32%) with a median duration of 4.2 mo (95% CI 3.5-4.8) and a median dose of 800 mg (95% CI 631-800). In the 99 pts starting CABO, 128 treatment-emergent adverse events (TEAE) of grade > 2 were reported, 40 of them classified as TRAE: hand foot skin reaction (14%), diarrhea (11%), asthenia and/or anorexia and/or weight loss (12%), arterial hypertension (4%). The ORR was 7% with 58% of disease control rate (DCR). Median PFS was 6.2 mo (95% CI, 5.3-8.7), TTP 8.2 mo (95% CI 6.1-12.8), without any difference when CABO used in 2L or 3L line (with prior IO [11%] or not). OS was 11.5 mo (95% CI 9.2-14.6) since start of CABO and 23 mo (95% CI 17.3-29.4) since the first systemic line. ALBI score at 1 was an independent marker of better OS in multivariate analysis (Exp[b] 3.26, 95% CI 1.86-5.69, p

BACKGROUND The Enhanced Liver Fibrosis score (ELF) and the FibroMeterV2G are two specialized blood fibrosis tests which include direct markers of liver fibrosis. They have been shown to be more accurate than the simple blood fibrosis tests FIB4 and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). AIMS To directly compare the accuracies of ELF and FibroMeterV2G for the non-invasive diagnosis of liver fibrosis in NAFLD. METHODS Four hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeterV2G , NFS, and FIB4. Advanced fibrosis F3/4 on liver biopsy (NASH CRN scoring) was the primary endpoint. RESULTS Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeterV2G (0.804 ± 0.021) had significantly higher AUROC than NFS (0.722 ± 0.025, P

Trans-acting splicing factors (SF) shape the eukaryotic transcriptome by regulating alternative splicing (AS). This process is recurrently modulated in liver cancer suggesting its direct contribution to the course of liver disease. The aim of our study was to investigate the relationship between the regulation of SFs expression and liver damage. The expression profile of 10 liver-specific SF and the AS events of 7 genes associated with liver disorders was assessed by western-blotting in 6 murine models representing different stages of liver damage, from inflammation to hepatocellular carcinoma (HCC). Relevant SFs (PSF, SRSF3, and SRSF6) and target genes (INSR, SRSF3, and SLK) modulated in mice were investigated in a cohort of 179 HCC patients. Each murine model of liver disease was characterized by a unique SF expression profile. Changes in the SF profile did not affect AS events of the selected genes despite the presence of corresponding splicing sites. In human HCC expression of SFs, including the tumor-suppressor SRSF3, and AS regulation of genes studied were frequently upregulated in tumor versus non-tumor tissues. Risk of tumor recurrence positively correlated with AS isoform of the INSR gene. In contrast, increased levels of SFs expression correlated with an extended overall survival of patients. Dysregulation of SF expression is an early event occurring during liver injury and not just at the stage of HCC. Besides impacting on AS regulation, overexpression of SF may contribute to preserving hepatocyte homeostasis during liver pathogenesis.

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.

Acute kidney injury (AKI) is common in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed new definitions of AKI in order to improve the prediction of outcomes. Our aim was to assess the prevalence and prognostic value of ICA 2015 - AKI criteria in hospitalised patients with cirrhosis.We prospectively collected data from 405 consecutive cirrhotic patients admitted to the hospital between November 2016 and November 2017. AKI was diagnosed at inclusion according to ICA 2015 criteria, and was assessed to predict 30-day and 90-day in-hospital mortality.AKI was diagnosed in 78 (19.3%) patients. AKI was independently associated with 90-day death (HR 7.61; 95% CI 4.75-12.19; p 0.001). In hospital, 30-day and 90-day survival was lower in the group of patients with AKI compared to the group with no AKI (72% vs. 98%, p 0.001; 64% vs. 96%, p 0.001; and 49% vs. 81%, p 0.001, respectively). Patients with stage 1a AKI had a lower 30-day and 90-day survival compared to the group of patients who did not develop AKI (71% vs. 96%, p 0.001, and 71% vs. 91%, p 0.01, respectively) and better survival than patients with more severe AKI (71% vs. 40%, p 0.01).AKI was independently associated with mortality in patients with cirrhosis, even at the very early 1a stage. Response to treatment improved survival, and was inversely proportional to the stage of AKI, which suggests that treatment should be started at the earliest stage of AKI.

International audience; BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study’s conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.

Hepatitis E virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis with an estimated 3.3 million symptomatic cases every year and 44,000 related deaths. It is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects resulting in significant mortality in pregnant women and patients with cirrhosis. In developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. HEV can also cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnosis is based on both anti-HEV IgM antibodies in serum and viral RNA detection in blood or stools by PCR in immunocompetent patients, while only PCR is validated in immunocompromised individuals. Ribavirin is the only validated treatment in chronic infection. A vaccine has been developed in China.

Background Anastomotic biliary strictures (AS) is the main surgical complication after liver transplantation. The aims of this study are to investigate the risk factors of AS, its management and its impact on overall survival and survival of the graft. Methods All patients who had received a liver transplantation with duct-to-duct anastomosis at Toulouse University Hospital between 2010 and 2016 were included. Results Of 225 included patients, 56 (24.9%) presented with AS. The median time to discovery of AS was 83 days and 69.6% of the AS appeared within 6 months. Transplantation in critically ill patients, with a liver score >800 points, was an independent predictive factor of survival (P = 0.003). The first-line treatment was endoscopic (87.5%), with a success rate of 79.6% and a median of 4 procedures per patient in 12 months. In cases of failure of endoscopic therapy, percutaneous treatment had a high failure rate (50%). AS had no impact in terms of overall survival or in terms of graft survival. Conclusion AS do not have any repercussions on patient or graft survival, requiring long endoscopic treatment with multiple procedures. In the event of failure of this first-line endoscopic treatment, it seems preferable to turn directly towards surgical repair.

International audience; Hepatitis E Virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 70 000 deaths. Hepatitis E is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects, resulting in significant mortality in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. The prevalence of positive HEV viraemia in blood donors in Europe ranges from 1/600 to 1/2500 in highly endemic European countries. HEV can cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnostic tools include anti-HEV IgM antibodies in serum and/or viral RNA detection in the blood or the stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China.

Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.

Background and objectives Noncirrhotic nontumoral extrahepatic portal vein obstruction (EHPVO) is the second leading cause of portal hypertension (PHT) and is mainly related to prothrombotic disorders. Patients with EHPVO often require prolonged oral anticoagulation therapy (OAT) together with variceal band ligation (VBL) to prevent thrombosis recurrence and PHT-related bleeding, respectively. The benefit-risk balance of VBL in this context remains unknown. We aimed to assess upper gastrointestinal bleeding (UGB) risk and variceal eradication efficacy in EHPVO patients undergoing a VBL program without stopping OAT. Patients and methods All patients with EHPVO treated (group A) or not (group B) with OAT and undergoing the VBL program were included between 2001 and 2010 in two tertiary French liver centers. We compared the incidence, source, and severity of UGB and variceal eradication efficacy. All EHPVO patients were then matched 1 : 1 with compensated cirrhotic patients with PHT not receiving OAT (group C) to compare UGB incidence and VBL efficacy. Results Forty-three EHPVO patients (30 with and 13 without OAT) and 43 cirrhotic patients were included for a total of 471 VBL sessions. The incidence of UGB was similar between group A (nine episodes/121 sessions) and group B (6/130), and tended to be higher in EHPVO patients (group A and B) than in cirrhotic patients (2/220). There was no difference between groups when considering bleeding source or severity and variceal eradication efficacy (84%). Conclusion VBL can be performed safely and efficiently without stopping anticoagulation therapy in EHPVO patients.

International audience; Hepatitis E virus (HEV), as a hepatotropic virus, is supposed to exclusively infect the liver and only cause hepatitis. However, a broad range of extrahepatic manifestations (in particular, idiopathic neurological disorders) have been recently reported in association with its infection. In this study, we have demonstrated that various human neural cell lines (embryonic stem cell-derived neural lineage cells) induced pluripotent stem cell-derived human neurons and primary mouse neurons are highly susceptible to HEV infection. Treatment with interferon-α or ribavirin, the off-label antiviral drugs for chronic hepatitis E, exerted potent antiviral activities against HEV infection in neural cells. More importantly, in mice and monkey peripherally inoculated with HEV particles, viral RNA and protein were detected in brain tissues. Finally, patients with HEV-associated neurological disorders shed the virus into cerebrospinal fluid, indicating a direct infection of their nervous system. Thus, HEV is neurotropic in vitro, and in mice, monkeys, and possibly humans. These results challenge the dogma of HEV as a pure hepatotropic virus and suggest that HEV infection should be considered in the differential diagnosis of idiopathic neurological disorders.

The Enhanced Liver Fibrosis score (ELF) and the FibroMeterTo directly compare the accuracies of ELF and FibroMeterFour hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeterAreas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeterELF and FibroMeter

ObjectiveHepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells.DesignWe developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions.ResultsPrimary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient.ConclusionHEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

International audience; BACKGROUND:Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients.METHODS:Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate.RESULTS:Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18).CONCLUSIONS:Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.

To enhance clinician's decision-making by diagnosing hepatocellular carcinoma (HCC) in cirrhotic patients with indeterminate liver nodules using quantitative imaging features extracted from triphasic CT scans.We retrospectively analyzed 178 cirrhotic patients from 27 institutions, with biopsy-proven liver nodules classified as indeterminate using the European Association for the Study of the Liver (EASL) guidelines. Patients were randomly assigned to a discovery cohort (142 patients (pts.)) and a validation cohort (36 pts.). Each liver nodule was segmented on each phase of triphasic CT scans, and 13,920 quantitative imaging features (12 sets of 1160 features each reflecting the phenotype at one single phase or its change between two phases) were extracted. Using machine-learning techniques, the signature was trained and calibrated (discovery cohort), and validated (validation cohort) to classify liver nodules as HCC vs. non-HCC. Effects of segmentation and contrast enhancement quality were also evaluated.Patients were predominantly male (88%) and CHILD A (65%). Biopsy was positive for HCC in 77% of patients. LI-RADS scores were not different between HCC and non-HCC patients. The signature included a single radiomics feature quantifying changes between arterial and portal venous phases:A signature using a single feature was validated in a multicenter retrospective cohort to diagnose HCC in cirrhotic patients with indeterminate liver nodules. Artificial intelligence could enhance clinicians' decision by identifying a subgroup of patients with high HCC risk.• In cirrhotic patients with visually indeterminate liver nodules, expert visual assessment using current guidelines cannot accurately differentiate HCC from differential diagnoses. Current clinical protocols do not entail biopsy due to procedural risks. Radiomics can be used to non-invasively diagnose HCC in cirrhotic patients with indeterminate liver nodules, which could be leveraged to optimize patient management. • Radiomics features contributing the most to a better characterization of visually indeterminate liver nodules include changes in nodule phenotype between arterial and portal venous phases: the "washout" pattern appraised visually using EASL and EASL guidelines. • A clinical decision algorithm using radiomics could be applied to reduce the rate of cirrhotic patients requiring liver biopsy (EASL guidelines) or wait-and-see strategy (AASLD guidelines) and therefore improve their management and outcome.

BACKGROUND AND OBJECTIVES To analyze overall survival (OS) rates for the three curative treatments of hepatocellular carcinoma (HCC) on an intention-to-treat (ITT) basis. METHODS Cohort study based on data from a multidisciplinary team meeting (MDT) dedicated to HCC. From 2006 to 2013, we included every patient with newly diagnosed HCC, for whom curative treatment (liver transplantation (LT), radiofrequency ablation (RFA), surgical resection (SR)) was decided upon. RESULTS We included 387 consecutive patients. LT was decided in 136 cases, RFA in 131 cases, SR in 120 cases. Sixty-six percent of patients received the planned treatment. Five-year OS on an ITT basis were: 35% for the LT-group, 32% for the RFA-group, 34% for the SR-group (P = 0.77). In multivariate analyses, the main negative prognostic factors were not following the MDT decision (HR: 0.39, CI95% [0.27-0.54], P

Hepatitis E virus (HEV) infection is a worldwide disease. It is the first cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 56 000 deaths. In developing countries, hepatitis E is a waterborne infection. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects with a significant mortality rate in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. HEV can cause neurological disorders and in immunocompromised patients, chronic infections. The progression of acute hepatitis E is most often mild and resolves spontaneously. Diagnostic tools include anti-HEV IgM antibodies in serum and/or viral RNA in the blood or stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China.

Background: In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre‐existing chronic liver disease (CLD). Aim: To determine the role of HEV in patients with decompensated CLD. Methods: Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow‐up for 6 months or death. IgG seroprevalence was compared with 911 controls. Results: 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28–4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2–30) and Truro (OR 2.5, 95% CI 1.4–4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41–0.86). Conclusions: Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location.

Background The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. Aims To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. Methods 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. Results The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness ( C -statistics = 0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy > 80%), but were not statistically superior to liver stiffness alone. Conclusions Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

The reduction of immunosuppressive therapy is the first-line therapeutic option in transplant-patients with chronic hepatitis E virus infection. Pegylated-interferon has been used for treating hepatitis E virus infection. Ribavirin alone is the treatment of choice of hepatitis E virus infection. Ribavirin is efficient for treating chronic hepatitis E in transplant patients, HIV patients, and hematology patients receiving or not chemotherapy. Ribavirin should be given to patients presenting hepatitis E virus associated extra-hepatic manifestations. The place of ribavirin therapy at acute phase is yet to be determined.

Summary Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver–kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney–liver transplantation.

Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear. Methods: We conducted a retrospective European multicenter cohort study involving 21 rheumatology and internal medicine patients with HEV infection between April 2014 and April 2016. The underlying diseases included rheumatoid arthritis (n = 5), psoriatic arthritis (n = 4), other variants of chronic arthritis (n = 4), primary immunodeficiency (n = 3), systemic granulomatosis (n = 2), lupus erythematosus (n = 1), Erdheim&ndash, Chester disease (n = 1), and retroperitoneal fibrosis (n = 1). Results: HEV infection lasting longer than 3 months was observed in seven (33%) patients, including two (40%) patients with rheumatoid arthritis, three (100%) patients with primary immunodeficiency, one (100%) patient with retroperitoneal fibrosis and one (100%) patient with systemic granulomatosis. Patients with HEV infection lasting longer than 3 months were treated with methotrexate without corticosteroids (n = 2), mycophenolate mofetil/prednisone (n = 1), and sirolimus/prednisone (n = 1). Overall, 8/21 (38%) and 11/21 (52%) patients cleared HEV with and without ribavirin treatment, respectively. One patient experienced an HEV relapse after initially successful ribavirin therapy. One patient (5%) was lost to follow-up, and no patients died from hepatic complications. Conclusion: Rheumatology and internal medicine patients, including patients treated with methotrexate without corticosteroids, are at risk of developing chronic HEV infection. Rheumatology and internal medicine patients with abnormal liver tests should be screened for HEV infection.

Transjugular intrahepatic portosystemic shunts (TIPS) is a second-line treatment because of an increased incidence of overt hepatic encephalopathy (OHE). A better selection of patients to decrease this risk is needed and one promising approach could be the detection of minimal hepatic encephalopathy (MHE). The aim of the present prospective study was to determine whether pre-TIPS minimal hepatic encephalopathy was predictive of post-TIPS OHE and to compare Psychometric Hepatic Encephalopathy Sum Score (PHES) and the Critical Flicker Frequency (CFF) in this setting. From May 2008 to January 2011, 54 consecutive patients treated with TIPS were included. PHES and CFF were performed 1 to 7 days before and after TIPS at months 1, 3, 6, 9, and 12 or until liver transplantation or death. Before TIPS, MHE was detected by PHES and CFF in 33% and 39% of patients, respectively. After the TIPS procedure, 19 patients (35%) experienced a total of 64 episodes of OHE. OHE developed significantly more often in patients for whom an indication for TIPS had been refractory ascites, with a history of OHE or of renal failure, lower hemoglobin level, or MHE as diagnosed by CFF. Post-TIPS OHE was more accurately predicted by CFF than by PHES. Absence of MHE at CFF had a good negative predictive value (91%) for the risk of post-TIPS recurrent OHE, defined as the occurrence of three or more episodes of OHE or of one episode which lasted more than 15 days. The absence of pre-TIPS history of OHE and a CFF value equal to or greater than 39 Hz had a 100% negative predictive value for post-TIPS recurrent OHE. Conclusion: Aiming to decrease the rate of post-TIPS HE, the use of CFF could help selecting patients for TIPS. (Hepatology 2014;59:622–629)

To analyze overall survival (OS) rates for the three curative treatments of hepatocellular carcinoma (HCC) on an intention-to-treat (ITT) basis.Cohort study based on data from a multidisciplinary team meeting (MDT) dedicated to HCC. From 2006 to 2013, we included every patient with newly diagnosed HCC, for whom curative treatment (liver transplantation (LT), radiofrequency ablation (RFA), surgical resection (SR)) was decided upon.We included 387 consecutive patients. LT was decided in 136 cases, RFA in 131 cases, SR in 120 cases. Sixty-six percent of patients received the planned treatment. Five-year OS on an ITT basis were: 35% for the LT-group, 32% for the RFA-group, 34% for the SR-group (P = 0.77). In multivariate analyses, the main negative prognostic factors were not following the MDT decision (HR: 0.39, CI95% [0.27-0.54], P 0.001), elevated alpha-fetoprotein level (HR: 0.63, CI95% [0.45-0.87], P = 0.005), being outside the Milan criteria (HR: 0.45, CI95% [0.31-0.65], P 0.001). When curative treatment was performed, per-protocol 5-year OS were 64% for LT, 34% for RFA, 40% for SR.On an ITT basis, OS was similar whatever the type of curative treatment chosen in MDT. Negative prognostic factors were not following the MDT decision, elevated alpha-fetoprotein, being outside the Milan criteria. J. Surg. Oncol. 2017;115:330-336. © 2016 Wiley Periodicals, Inc.

International audience; Background & aims: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy.Methods: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA.Results: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed.Conclusions: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.

Background & Aims Refractory ascites in patients with cirrhosis is associated with poor survival. TIPS is more effective than para-centesis for the prevention of recurrence of ascites but increases the risk of encephalopathy while survival remains unchanged. A more accurate selection of the patients might improve these results. The aim of the present study was to identify parameters of prognostic value for survival in patients with refractory ascites treated with TIPS. Methods One hundred and five consecutive French patients with cirrhosis and refractory ascites treated with TIPS were used to assess parameters associated with 1-year survival. The model was then tested in two different cohorts: a local and prospective one including 40 patients from Toulouse, France, and an external one including 48 patients from Barcelona, Spain. Results The actuarial rate of survival in the first 105 patients was 60% at 1 year. Using multivariate analysis, only lower bilirubin levels and higher platelet counts were independently associated with survival. The actuarial 1-year survival rate in patients with both a platelet count above 75×10 9 /L and a bilirubin level lower than 50μmol/L [3mg/dl] was 73.1% as compared to 31.2%, in patients with a platelet count below 75×10 9 /L or a bilirubin level higher than 50μmol/L. These results were confirmed in the two different validation cohorts. Conclusions The combination of a bilirubin level below 50μmol/L and a platelet count above 75×10 9 /L is predictive of survival in patients with refractory ascites treated with TIPS. This simple score could be used at bedside to help choose the best therapeutic options.

International audience; Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies.

Background & Aims 30–40% of portal vein thrombosis (PVT) remains of unknown origin. An association between metabolic syndrome (MetS) and peripheral vein thrombosis has been reported but not with PVT, to date. The aim of this study was to investigate the association between MetS and PVT. Methods Between 2003 and 2014, all consecutive patients with non-cirrhotic PVT were prospectively included. Patient's characteristics and risks factors were recorded at the time of inclusion. Controls were selected by random in the general population and were matched 1/1 according to age and sex. Results Seventy-nine patients with PVT were included: 40 present with at least one risk factor for PVT (SPVT) and 39 were found to be idiopathic (IPVT). The prevalence of MetS was 25.6% in SPVT group vs. 47.4% in IPVT group and 17.9% in controls from the general population (C-IPVT: p =0.01). The waist circumference and body mass index were higher in the IPVT group than in the SPVT group (105 vs. 93cm, p =0.004 and 29.4 vs. 25.0kg/m 2 , p =0.004) and in the C-IPVT group (105 vs. 92cm, p =0.001 and 29.4 vs. 25.8kg/m 2 , p =0.003). Overweight was observed in 82.0% of patients in the IPVT group vs. 44% in the SPVT group ( p =0.002) and 51% in the C-IPVT group ( p =0.01). The mean visceral fat area was higher in IPVT than in SPVT (18,223mm 2 vs. 12,690mm 2 , p =0.02). In multivariate analyses, an increase in waist circumference was the strongest parameter associated with idiopathic PVT. Conclusion Central obesity is associated with PVT and could become one of the main risk factors for digestive thromboses.

The reduction of immunosuppressive therapy is the first-line therapeutic option in transplant-patients with chronic hepatitis E virus infection. Pegylated-interferon has been used for treating hepatitis E virus infection. Ribavirin alone is the treatment of choice of hepatitis E virus infection. Ribavirin is efficient for treating chronic hepatitis E in transplant patients, HIV patients, and hematology patients receiving or not chemotherapy. Ribavirin should be given to patients presenting hepatitis E virus associated extra-hepatic manifestations. The place of ribavirin therapy at acute phase is yet to be determined.

International audience; Background: The aetiologies of acute pancreatitis in young adult patients are poorly known.Aims: To prospectively evaluate the causes of acute pancreatitis in patients aged less than 35 years.Methods: Overall, 309 consecutive patients admitted to our centre for acute pancreatitis received first-line investigations, including medical history, standard laboratory tests, abdominal ultrasound and computed tomography. If no aetiology was found, second-line investigations were performed, including endoscopic ultrasound, magnetic-resonance cholangiopancreatography and genetic testing in cases of idiopathic pancreatitis.Results: Overall, 66 patients aged between 16 and 35 years were included. After first-line investigations, 49% of cases of acute pancreatitis remained idiopathic. Second-line investigations reduced this rate to 21%. The frequency of aetiologies for acute pancreatitis significantly differed in adults aged ≤ 35 compared to those aged >35 years: biliary aetiology was less frequent (23% versus 43%, p=0.003) as well as alcohol-related (8% versus 24%, p=0.01); drug-induced was more common (16% versus 4%, p=0.0007), as well as cannabis-related (13% versus 1%, p

*University of Medicine and Pharmacy ‘Iuliu Hatieganu’, 3rd Medical Clinic, Department of Gastroenterology, Cluj-Napoca, Romania. Regional Institute of Gastroenterology and Hepatology ‘O Fodor’, Department of Gastroenterology, Cluj-Napoca, Romania. Department of Hepato-Gastroenterology, Purpan Hospital, CHU, Toulouse, France. INSERM U858 and University of Toulouse, Toulouse, France. E-mail: bogdanprocopet@gmail.com

International audience; New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (800-1200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum ribavirin and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age=49, range [31-76]) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/mL and the HCV genotypes were: G1 (n=93) with 1a (n=37) and 1b (n=50), G4 (n=20) and G5 (n=2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR=2.98 [1.15; 7.72]) and ribavirin of > 2,200 ng/mL at week 12 (OR=3.41 [1.31; 8.90]). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR=6.82 [1.7; 26.8]), and HCV RNA 2,200 ng/mL was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.