A. Abergel

Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir)

The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)‐compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Coxs multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow‐up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm3: HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm3: HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma‐glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow‐up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11‐point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. Conclusion: This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136‐1147)

Large balloon dilation post endoscopic sphincterotomy in removal of difficult common bile duct stones: a literature review.

Endoscopic sphincterotomy (ES) is the standard therapy in common bile duct (CBD) stones extraction. Large stones (≥ 12 mm) or multiple stones extraction may be challenging after ES alone. Endoscopic sphincterotomy followed by large balloon dilation (ESLBD) has been described as an alternative to ES in these indications. Efficacy, safety, cost-effectiveness and technical aspects of the procedure have been here reviewed. PubMed and Google Scholar search resulted in forty-one articles dealing with CBD stone extraction with 12 mm or more dilation balloons after ES. ESLBD is at least as effective as ES, and reduces the need for additional mechanical lithotripsy. Adverse events rates are not statistically different after ESLBD compared to ES for pancreatitis, bleeding and perforation. However, particular attention should be paid in patients with CBD strictures, which is identified as a risk factor of perforation. ESLBD is slightly cost-effective compared to ES. A small sphincterotomy is usually performed, and may reduce bleeding rates compared to full sphincterotomy. Dilation is performed with 12-20 mm enteral balloons. Optimal inflation time is yet to be determined. The procedure can be performed safely even in patients with peri-ampullary diverticula and surgically altered anatomy. ESLBD is effective and safe in the removal of large CBD stones, however, small sphincterotomy might be preferred and CBD strictures should be considered as a relative contraindication.

Long-term outcome of endoscopic ultrasound-guided pelvic abscess drainage: a two-center series

Background and study aim Endoscopic ultrasound (EUS)-guided pelvic abscess drainage has been reported but long-term data remain limited. This two-center study evaluated long-term outcome of EUS-guided pelvic abscess drainage. Patients and methods Between May 2003 and December 2015, 37 consecutive patients were treated for perirectal or perisigmoid abscesses via EUS-guided drainage using plastic or lumen-apposing metal stent (LAMS). Clinical success was defined as complete resolution of the abscess on follow-up computed tomography (CT) scan at 4 weeks with symptom relief. Long-term success was defined as abscess resolution without the need for surgery and without recurrence on long-term follow-up (> 12 months). Results Median abscess size was 60 mm (interquartile range 41 - 70). Causes were postsurgical (n = 31, 83.8 %) or secondary to medical conditions (n = 6, 16.2 %). EUS-guided drainage involved needle aspiration (n = 4), plastic stent placement (n = 29) or LAMS placement (n = 4 patients). Technical and clinical success was achieved in 37 patients (100 %; 95 % confidence interval [CI] 91 - 100) and 34 patients (91.9 %; 95 %CI 78 - 98), respectively (5 patients needed a second EUS-guided intervention within 14 days after drainage). One patient required surgery and one required best supportive care owing to persistent abscess. Early complications were perforation requiring surgery (n = 1), stent migration (n = 1), and rectal discomfort (n = 1). At a median follow-up of 64 months (IQR 19 - 81), two patients experienced abscess recurrence, at 3 and 12 months, respectively, and were treated surgically. Long-term success was achieved in 32 of 37 patients (86.5 %; 95 %CI 71 - 95). Conclusion EUS-guided drainage of pelvic abscess is safe, has good long-term outcome, and should be considered as an alternative to percutaneous and surgical drainage.

Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts 1H-NMR Spectroscopy

There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n = 6) and NAFLD (n = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes.

Plasma hypercoagulability in the presence of thrombomodulin but not of activated protein C in patients with cirrhosis.

Cirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this phenotype. The aim of this study was to compare the results of thrombin generation assays performed with addition of thrombomodulin or activated protein C to assess the effect of by‐passing the protein C activation step in cirrhotic patients and healthy controls.

P1288 : Budd chiari syndrome (BCS) in France from a large national cohort

increased in recent years. This increase may be due to factors such as high HCV viral load in blood and semen, sex with risk of mucosal damage, a higher number of sexual partners, presence of concomitant ulcerative sexually transmitted diseases and the use of recreational drugs. The aim of our study was to investigate the dynamics of HCV transmission in an outbreak of acute hepatitis C in HIV-infected MSM in Barcelona. Methods: Between 2008 and 2013, 113 cases of acute hepatitis C in HIV-infected MSM were diagnosed in the Infectious Diseases Unit, Hospital Clinic, Barcelona. Phylogenetic analysis of the HCV NS5B gene was performed in a total of 70 patients. Viral RNA was extracted from serum samples collected from each patient at the time of diagnosis. Massive sequencing was performed using the Roche 454 GS Junior platform. To define possible transmission networks, phylogenetic trees and multidimensional scaling maps were constructed from genetic distance matrices (Da). Results: At the time of diagnosis of acute hepatitis C, 53 of the 70 (76%) patients included in the study were receiving antiretroviral therapy. HIV viral load was undetectable in 48 patients (69%) and the mean CD4 cell count was 923 cells /ul. HCV viral load was 6.37 log IU/mL (range 3.73–6.99). Thirty-five of 53 (66%) patients treated with pegIFN and ribavirin achieved a sustained virological response. The prevalence of HCV genotypes was: 4d 51% (n =36), 1a 40% (n =28), 1b 7% (n =5) and 3a 1% (n =1). Phylogenetic analysis showed the existence of at least 13 monophyletic groups: 5 of genotype 1a, 2 of genotype 1b and 6 genotype 4d. Molecular analysis showed that the genetic distances between genotype 4d viruses (Da 5.42) were significantly lower than those of the subtypes 1a (Da 18.50, p < 2.2×10−16) and 1b (Da 15.25, p < 1.1×10−6). This result may suggest the existence of a single source of infection for genotype 4d and different sources for subtypes 1a and 1b. Conclusions: HCV infection spreads rapidly among HIV-infected MSM through a local network in Barcelona. The implementation of public health campaigns and preventive measures, as well as treatment interventions with the new direct-acting antivirals will allow the development of strategies to reduce the HCV transmission of HCV within these high-risk groups.

Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis

Essentials The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated. Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin. Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hypercoagulability. Only protein C and factor VIII normalization led to thrombin generation similar to controls.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir‐based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable.

Usefulness of the Hook knife in flexible endoscopic myotomy for Zenker’s diverticulum

AIM To investigate the outcome of flexible endoscopic myotomy performed with the Hook knife in patients with symptomatic Zenker’s diverticulum (ZD). METHODS All consecutive patients treated for ZD at our institution between 7/2012 and 12/2016 were included. The flexible endoscopic soft diverticuloscope-assisted technique with endoclips placement and Hook knife myotomy were performed in all patients. Here we report a retrospective review of prospectively collected data. Demographics, dysphagia score (Dakkak and Bennett), associated symptoms and adverse events were collected pre-procedure, at 2 and 6 mo post-procedure, and at the end of the follow-up period. Clinical success was defined as at least 1-point improvement in dysphagia score and a residual dysphagia score ≤ 1, with no need for reintervention. Dysphagia scores were compared before treatment and at end-of-follow-up using the Wilcoxon test. RESULTS Twenty-four patients were included. Mean size of ZD was 3.0 cm (range 2-8 cm). Mean number of sessions was 1.17/patient (range 1-3 sessions). Overall clinical success was 91.7%. Two adverse events (8.3%) occurred, and both were managed conservatively. No bleeding or perforation was reported. Mild pain was reported by 9 patients (37.5%). Median hospital stay was 1 d (range 1-6). Median follow-up was 19.5 mo (range 6-53). Mean ± SD dysphagia score was 2.25 ± 0.89 before treatment and decreased to 0.41 ± 0.92 at end-of-follow-up (P < 0.001). Regurgitation and cough dropped from 91.7% and 50% to 12.5% and 0% at the end of follow-up, respectively. Recurrence was observed in 3 patients, and all 3 were symptom-free after one more session. CONCLUSION The Hook knife, used in the soft diverticuloscope-assisted technique setting, is efficient and safe for treatment of ZD.

Interventional endoscopic ultrasound: A new promising way for intrahepatic portosystemic shunt with portal pressure gradient

Background and Objectives: Interventional endoscopic ultrasound (EUS) is a promising novel approach for intravascular interventions. The aim of this study was to assess the feasibility and safety of a EUS-guided intrahepatic portosystemic shunt (EGIPS) with portal pressure gradient measurement in a live porcine model. Methods: The left hepatic vein (LHV) or the inferior vena cava (IVC) was punctured with a needle that advanced into the portal vein (PV). A guidewire was then inserted into the PV, and a needle knife was used to create an intrahepatic fistula between LHV and PV. Portal pressure was recorded. The fistula was dilated with a balloon and a biliary metal stent was deployed between LHV and PV under sonographic and fluoroscopic observation. A portocavography validated the patency of the stent. Necropsies were realized after euthanasia. Results: Portosystemic stenting was achieved in 19/21 pigs. Final portocavography confirmed stent patency between PV and LHV or IVC in 17 pigs (efficacy of 81%): Four stents were dysfunctional as two were thrombosed and two were poor positioned. Portal pressure was documented before and after shunting in 20/21 pigs. Necropsies revealed that 19/21 procedures were transesophageal and two were transgastric. Hemoperitoneum and pneumothorax were found in one pig and hemothorax was found in two pigs. Morbidity was 14.2% (3/21 animals). Conclusion: EGIPS was feasible in 91% of cases, functional in 81%, with 14.2% per procedure morbidity. EGIPS still needs to be assessed in portal hypertension pig models with longer follow-up before being considered as an alternative when the transjugular intrahepatic portosystemic shunt fails.