Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Early detection of liver injuries by the Serum enhanced binding test sensitive to albumin post-transcriptional modifications.

Early and sensitive biomarkers of liver dysfunction and drug-induced liver injury (DILI) are still needed, both for patient care and drug development. We developed the Serum Enhanced Binding (SEB) test to reveal post-transcriptional modifications (PTMs) of human serum albumin resulting from hepatocyte dysfunctions and further evaluated its performance in an animal model. The SEB test consists in spiking serum ex-vivo with ligands having specific binding sites related to the most relevant albumin PTMs and measuring their unbound fraction. To explore the hypothesis that albumin PTMs occur early during liver injury and can also be detected by the SEB test, we induced hepatotoxicity in male albino Wistar rats by administering high daily doses of ethanol and CCl4 over several days. Blood was collected for characterization and quantification of albumin isoforms by high-resolution mass spectrometry, for classical biochemical analyses as well as to apply the SEB test. In the exposed rats, the appearance of albumin isoforms paralleled the positivity of the SEB test ligands and histological injuries. These were observed as early as D3 in the Ethanol and CCl4 groups, whereas the classical liver tests (ALT, AST, PAL) significantly increased only at D7. The behavior of several ligands was supported by structural and molecular simulation analysis. The SEB test and albumin isoforms revealed hepatocyte damage early, before the current biochemical biomarkers. The SEB test should be easier to implement in the clinics than albumin isoform profiling.

Risk of delayed bleeding after colorectal endoscopic submucosal dissection: the Limoges Bleeding Score.

BACKGROUND: Clinically significant delayed bleeding (CSDB) is a frequent, and sometimes severe, adverse event after colorectal endoscopic submucosal dissection (ESD). We evaluated risk factors of CSDB after colorectal ESD. METHODS: We analyzed a prospective registry of 940 colorectal ESDs performed from 2013 to 2022. The incidence of bleeding was evaluated up to 30 days. Risk factors for delayed bleeding were evaluated by multivariate logistic regression. A Korean scoring model was tested, and a new risk-scoring model was developed and internally validated. RESULTS: CSDB occurred in 75 patients (8.0%). The Korean score performed poorly in our cohort, with a receiver operating characteristic (ROC) curve of 0.567. In the multivariate analysis, risk factors were age ≥75 years (odds ratio [OR] 1.63; 95%CI 0.97-2.73; 1 point), use of antithrombotics (OR 1.72; 95%CI 1.01-2.94; 1 point), rectal location (OR 1.51; 95%CI 0.92-2.48; 1 point), size >50 mm (OR 3.67; 95%CI 2.02-7.14; 3 points), and American Society of Anesthesiologists (ASA) score of III or IV (OR 2.26; 95%CI 1.32-3.92; 2 points). The model showed fair calibration and good discrimination, with an area under the ROC curve of 0.751 (95%CI 0.690-0.812). The score was used to define two groups of patients, those with low-medium risk (0 to 4 points) and high risk (5 to 8 points) for CSDB (respective bleeding rates 4.1% and 17.5%). CONCLUSION: A score based on five simple and meaningful variables was predictive of CSDB.

Prevalence and clinical significance of the muscle retracting sign during endoscopic submucosal dissection of large macronodular colorectal lesions (with videos).

BACKGROUND AND AIMS: The muscle retracting sign (MRS) can be present during endoscopic submucosal dissection (ESD) of macronodular colorectal lesions. The prevalence of MRS and its pathologic and clinical implications is unclear. This study evaluated the effect of MRS on the technical and clinical outcomes of ESD. METHODS: All patients referred for ESD of protruding lesions or granular mixed lesions with >10 mm macronodule granular mixed laterally spreading tumors (LST-GMs) in 2 academic centers from January 2017 to October 2022 were prospectively included. Size of the macronodule was analyzed retrospectively. The primary outcome was the curative resection rate according to MRS status. Secondary outcomes were R0 resection, perforation, secondary surgery rate, and risk factors for MRS. RESULTS: Of 694 lesions, 84 (12%) had MRS (MRS+). The curative resection rate was decreased by MRS (MRS+ 41.6% vs lesions without MRS [MRS-] 81.3%), whereas the perforation (MRS+ 22.6% vs MRS- 9.2%), submucosal cancer (MRS+ 34.9% vs MRS- 9.2%), and surgery (MRS+ 45.2% vs MRS- 6%) rates were increased. The R0 resection rate of MRS+ colonic lesions was lower than that of rectal lesions (53% vs 74.3%). In multivariate analysis, protruding lesions (odds ratio, 2.47; 95% confidence interval, 1.27-4.80) and macronodules >4 cm (odds ratio, 4.24; 95% confidence interval, 2.23-8.05) were risk factors for MRS. CONCLUSIONS: MRS reduces oncologic outcomes and increases the perforation rate. Consequently, procedures in the colon should be stopped if MRS is detected, and those in the rectum should be continued due to the morbidity of alternative therapy.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Towards hepatitis C elimination in France: Scanvir, an effective model to test and treat drug users on dedicated days.

According to the French recommendations, the elimination of the hepatitis C virus by 2025 could be a realistic public health goal. Screening policies are being intensified, and access to treatment is promoted for patients who escape the usual care pathway. The 'Scanvir' program is an original strategy based on dedicated screening days, as part of the 'test, treat and cure HCV' event in addiction care centers in a French region, during which innovative screening technologies (RDTs, FibroScan® and point-of-care HCV RNA testing) are brought on site and access to a multidisciplinary team is offered. A total of 392 patients attended the 67 regional Scanvir sessions: 31.6% were HCV Ab-positive and 66% of them were HCV RNA-positive. Treatment was initiated in 79.3% of the patients. RDTs were accepted by 62% of the PWIDs (including those who already knew their status) and FibroScan® by 99.5% of the patients. 80% of the viremic patients started their treatment on site and are now cured or still under treatment. Advanced fibrosis evaluated by FibroScan® (LSM > 8 KPa) was suspected in 13.4% and 14.1% of the global and the HCV population, respectively. Scanvir is an efficient strategy for HCV elimination based on dedicated days aimed at increasing cost-effectiveness and offering a multidisciplinary service while saving human care resources. It is an exportable strategy that also offers comprehensive screening of associated chronic liver diseases via the elastometry device and interviews.

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH.

BACKGROUND & AIMS: The LIVIFY trial investigated the safety, tolerability, and efficacy of vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH). METHODS: This double-blind phase IIa study was conducted in two parts. Patients were randomised (1:1:1:1) to receive placebo, vonafexor 100 mg twice daily (VONA-100BID), vonafexor 200 mg once daily (VONA-200QD), or 400 mg vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B. The primary efficacy endpoint was a reduction in liver fat content (LFC) by MRI-proton density fat fraction, while secondary endpoints included reduced corrected T1 values and liver enzymes, from baseline to Week 12. RESULTS: One hundred and twenty patients were randomised (Part A, n = 24; Part B, n = 96). In Part B, there was a significant reduction in least-square mean (SE) absolute change in LFC from baseline to Week 12 for VONA-100QD (-6.3% [0.9]) and VONA-200QD (-5.4% [0.9]), vs. placebo (-2.3% [0.9], p = 0.002 and 0.012, respectively). A >30% relative LFC reduction was achieved by 50.0% and 39.3% of patients in the VONA-100QD and VONA-200QD arms, respectively, but only in 12.5% in the placebo arm. Reductions in body weight, liver enzymes, and corrected T1 were also observed with vonafexor. Creatinine-based glomerular filtration rate improved in the active arms but not the placebo arm. Mild to moderate generalised pruritus was reported in 6.3%, 9.7%, and 18.2% of participants in the placebo, VONA-100QD, and VONA-200QD arms, respectively. CONCLUSIONS: In patients with suspected fibrotic NASH, vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit. CLINICAL TRIAL NUMBER (EUDRACT): 2018-003119-22. GOV IDENTIFIER: NCT03812029. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) has become a leading cause of chronic liver disease worldwide. Affected patients are also at higher risk of developing chronic kidney disease. There are no approved therapies and only few options to treat this population. The phase IIa LIVIFY trial results show that single daily administration of oral vonafexor, an FXR agonist, leads in the short term to a reduction in liver fat, liver enzymes, fibrosis biomarkers, body weight and abdominal circumference, and a possible improvement in kidney function, while possible mild moderate pruritus (a peripheral FXR class effect) and an LDL-cholesterol increase are manageable with lower doses and statins. These results support exploration in longer and larger trials, with the aim of addressing the unmet medical need in NASH.

Iohexol plasma and urinary concentrations in cirrhotic patients: A pilot study.

BACKGROUND: Renal failure is an independent prognostic factor for survival in patients with cirrhosis. Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate (GFR). Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population, but no study has simultaneously measured plasma and urinary clearance, which is the gold standard. AIM: To study calculated plasma and urinary concentrations of iohexol, based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites. METHODS: One dose of iohexol (5 mL) was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients. The urinary concentration of iohexol was also measured, in urine collected at 4, 8, 12 and 24 h. RESULTS: The plasma and urinary curves of iohexol were similar; however, incomplete urinary excretion was detected at 24 h. Within the estimated GFR limits of our population (> 30 and < 120 mL/min/1.73 m²), the median measured GFR (mGFR) was 63.7 mL/min/1.73 m² (range: 41.3-111.3 mL/min/1.73 m²), which was an accurate reflection of the actual GFR. Creatinine-based formulas for estimating GFR showed significant bias and imprecision, while the Brochner-Mortensen (BM) equation accurately estimated the mGFR (r = 0.93). CONCLUSION: Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade. We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

A Hybrid Model Associating Population Pharmacokinetics with Machine Learning: A Case Study with Iohexol Clearance Estimation.

BACKGROUND: Maximum a posteriori Bayesian estimation (MAP-BE) based on a limited sampling strategy and a population pharmacokinetic model is frequently used to estimate pharmacokinetic parameters in individuals, however with some uncertainty (bias). Recent works have shown that the performance in individual estimation or pharmacokinetic parameters can be improved by combining population pharmacokinetic and machine learning algorithms. OBJECTIVE: The objective of this work was to investigate the use of a hybrid machine learning/population pharmacokinetic approach to improve individual iohexol clearance estimation. METHODS: The reference iohexol clearance values were derived from 500 simulated profiles (samples collected between 0.1 and 24.7 h) using a population pharmacokinetic model we recently developed in Monolix and obtained using all the concentration timepoints available. Xgboost and glmnet algorithms able to predict the error of MAP-BE clearance estimates based on a limited sampling strategy (0.1 h, 1 h, and 9 h) versus reference values were developed in a training subset (75%) and were evaluated in a testing subset (25%) and in 36 real patients. RESULTS: The MAP-BE limited sampling strategy estimated clearance was corrected by the machine learning predicted error leading to a decrease in root mean squared error by 29% and 24%, and in the percentage of profiles with the mean prediction error out of the ± 20% bias by 60% and 40% in the external validation dataset for the glmnet and Xgboost machine learning algorithms, respectively. These results were attributable to a decrease in the eta-shrinkage (shrinkage for a MAP-BE limited sampling strategy = 32.4%, glmnet = 18.2%, and Xgboost = 19.4% in the external dataset). CONCLUSIONS: In conclusion, this hybrid algorithm represents a significant improvement in comparison to MAP-BE estimation alone.

Gastric peroral endoscopic myotomy in refractory gastroparesis: long-term outcomes and predictive score to improve patient selection.

BACKGROUND AND AIMS: Limited data exist concerning the long-term efficiency of gastric peroral endoscopic myotomy (G-POEM) as a treatment of refractory gastroparesis. This study evaluated the 3-year results of G-POEM in patients with refractory gastroparesis. METHODS: This was a prospective multicenter study of all G-POEM operations performed in 2 expert French centers for 46 patients with refractory gastroparesis with at least 3 years of follow-up. RESULTS: Clinical success was 65.2% at 36 months. There was significant improvement in symptom severity. Median Gastroparesis Cardinal Symptom Index decreased from 3.33 to 1.80 (P < .0001), with improvement in all subscales. We created a predictive score concerning G-POEM success (G-POEM predictive score) to which points were assigned as follows: nausea subscale <2: predictive of success, 1 point; satiety subscale >4: predictive of success, 1 point; bloating subscale >3.5: predictive of success, 1 point; percentage of gastric retention at 4 hours on scintigraphy >50%: 1 point. A threshold of 2 was identified by receiver operating characteristic curve analysis with an area under the curve of .825 that predicted clinical success with a sensitivity of 93.3% (95% confidence interval [CI], .77-.99), specificity of 56.3% (95% CI, .33-.77), positive predictive value of 80% (95% CI, .67-.93), negative predictive value of 81.8% (95% CI, .59-1.00), and accuracy of 80.4% (95% CI, .69-.92). Patients with a score ≥2 were significantly more likely to be responders at 3 years than were patients with a score <2 (80% and 18%, respectively; P = .0004). CONCLUSIONS: The clinical success of G-POEM for refractory gastroparesis was 65.2% at 36 months. Our predictive score offers an easy tool that needs to be confirmed in other studies.

Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis.

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 < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17-0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06-0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05-0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29-0.93, p = 0.03). 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.

A simple clinical score to promote and enhance ferroportin disease screening.

BACKGROUND & AIMS: Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening. METHODS: Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation. RESULTS: Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 µg/L, and liver iron concentration (LIC) 166±77 µmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37). CONCLUSION: We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice. LAY SUMMARY: Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients.

AIMS: Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. METHODS: Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. RESULTS: A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and body weight on Vd. The best LSS included samples at 0.1-1-9 h exhibiting a relative mean prediction error (MPE) (RMSE) = -3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (-3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9 hours for the third sample were associated with an increased imprecision. CONCLUSION: A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

Alpha-fetoprotein and focal nodular hyperplasia: An unconventional couple.

We report the case of a 36-year-old patient who was initially managed for gynecomastia. The first biological analyses showed a moderately elevated alpha-fetoprotein (AFP) level. After an endocrine etiology was excluded, an abdominal computed tomography scan showed typical focal nodular hyperplasia (FNH) proven by biopsy and showing expression of AFP in FNH cells. After follow-up for 24 months, the serum AFP and liver radiology remained unchanged. The association between an elevated AFP and FNH is rarely described in the medical literature.

Predictive factors for hepatocellular carcinoma in chronic hepatitis B using structural equation modeling: a prospective cohort study.

BACKGROUND & AIMS: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort. METHODS: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified. RESULTS: Among the 4489 patients included, 33 patients reported incident HCC. The median follow-up was 45.5 months. Age (ß = 0.18 by decade, 95% CI 0.14-0.23), male gender (ß = 0.23, 95% CI 0.18-0.29), metabolic syndrome (ß = 0.28, 95% CI 0.22-0.33), alcohol consumption (ß = 0.09, 95% CI 0.05-0.14) and HBV DNA (ß = 0.25, 95% CI 0.170.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (ß = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC. CONCLUSIONS: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.

Double-clip traction for colonic endoscopic submucosal dissection: a multicenter study of 599 consecutive cases (with video).

BACKGROUND AND AIMS: Colonic endoscopic submucosal dissection (ESD) is particularly challenging and limited to a few expert centers. We recently conducted a pilot study on improvement of colonic ESD with systematic use of a countertraction device (double-clip traction with rubber band [DCT-ESD]). METHODS: A French prospective multicenter study was conducted between March 2017 and September 2019, including all consecutive cases of naive colonic ESD. Since the first case of DCT-ESD in March 2017, all cases of colonic ESD have been performed using the DCT-ESD strategy in the 3 centers involved in the study. RESULTS: Five hundred ninety-nine lesions with a mean size of 53 mm were included in this study, resected by 5 operators in 3 centers. The en bloc, R0, and curative resection rates were 95.7%, 83.5%, and 81.1%, respectively. The adverse event rates were 4.9% for perforation and 4.2% for postprocedure bleeding. Between 2017 and 2019, the rates of R0 and curative resections increased significantly from 74.7% in 2017 to 88.4% in 2019 (P = .003) and from 72.6% in 2017 to 86.3% in 2019 (P = .004), respectively. Procedure duration and speed of resection were 62.4 minutes and 39.4 mm2/minute, respectively. No differences were noted between operators. CONCLUSION: DCT-ESD is a safe and reproducible technique, with results comparable with those of the large Japanese teams with speed of resection twice as high as previously reported studies. The DCT strategy is promising, cheap, and seems to be reproducible. Physicians performing colonic ESD should be aware of this promising tool to improve their results in ESD.

Double-clip traction could be superior to the pocket-creation method with cylindrical cap for colonic ESD: a randomized study in an ex vivo model.

INTRODUCTION: In Western countries, debates between ESD vs piece-meal EMR as the best treatment for large colorectal adenomas persist regarding the difficulty of ESD the colon, and the safety and relatively good results of piece-meal endoscopic mucosal resection (EMR). Pocket-creation method (PCM) and double-clip countertraction (DCT) are two strategies recently published to facilitate ESD in this challenging situation. METHOD: This is a randomized animal study to compare PCM and DCT strategies for colonic ESD on ex vivo models (bovine colon) performed by 3 operators novice in ESD. Hybridknife type T was used to inject normal saline tinted with a small amount of blue dye in all procedures. Randomization was stratified according to the use of gravity assist. Primary endpoint was the difference in resection speed between PCM and DCT strategies. RESULTS: Resection speed was significantly higher in the DCT group than in the PCM group (56.3 vs. 31.6 mm2/min, p = 0.01). Technical success rate, defined as en bloc resection in under 60 min, was significantly better in the DCT group than in the PCM group (100% vs. 84.4%, p = 0.024), perforation rate was lower (0% vs. 18.8%, p = 0.012), and difficulty score was better (2.4 vs. 6.2, p < 0.0001) as was procedure duration (24.2 vs. 40.2 min, p < 0.0001). CONCLUSION: DCT was superior to PCM for ESD in our validated bovine colon model. This strategy is inexpensive, easy to use and adaptive. It might facilitate the widespread use of colonic ESD in Western countries and change Western ideas regarding the use of colonic ESD compared with piece-meal EMR for large benign lesions.

Abdominal symptoms during Sjogren's syndrome: a pilot study.

BACKGROUND: Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease. METHODS: One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected. RESULTS: Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each). CONCLUSIONS: The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms. TRIAL REGISTRATION: NCT03157011 . Date of registration: July 17, 2017.