Publications by authors named "Dominique Thabut"

187 Publications

A systemic mechanism of increased transendothelial migration of leukocytes through the blood-brain barrier in hepatic encephalopathy.

Clin Res Hepatol Gastroenterol 2021 Sep 10:101801. Epub 2021 Sep 10.

Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), F-75012 Paris, France; AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Service d'Hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE), F-75013 Paris, France. Electronic address:

Background: Hepatic encephalopathy (HE) is a frequent neurological complication of cirrhosis. Evidence suggests a synergic pathophysiological implication of hyperammonemia and systemic inflammation. In addition, the blood-brain barrier (BBB) permeability can be impaired in cirrhotic patients, notably in those displaying HE. We hypothesized that systemic inflammation could trigger leukocytes transendothelial migration (TEM) through the BBB in cirrhotic patients and especially those with HE.

Methods: We studied the effects of patients' plasma on the TEM of the leukocyte U937 cell line in vitro, using a validated BBB model (hCMEC/D3 cell line). We compared TEM of U937 leukocytes across hCMEC/D3 monolayer incubated with the plasma of i) patients with cirrhosis without HE, ii) patients with cirrhosis and HE, iii) healthy controls.

Results: We show that the plasma of cirrhotic patients with HE enhances TEM of U937 leukocytes across hCMEC/D3 BBB model. We found a correlation between U937 TEM on the one hand, the West-Haven score and ammonemia on the other one. A trend towards a correlation between U937 TEM and PS-100Beta in plasma, a marker of BBB solute's permeability increase, was also found.

Conclusion: These findings suggest that circulating factors could increase leukocytes TEM in cirrhotic patients and contribute to the increased BBB permeability that has been described in cirrhotic patients with HE.
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http://dx.doi.org/10.1016/j.clinre.2021.101801DOI Listing
September 2021

Standardization of the psychometric hepatic encephalopathy score in a French population.

PLoS One 2021 10;16(9):e0257136. Epub 2021 Sep 10.

Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France.

The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20-29 to 80-89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257136PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432843PMC
September 2021

Portal hypertension, advanced hepatocellular carcinoma and therapy by atezolizumab-bevacizumab: a "menage à trois" !

Clin Res Hepatol Gastroenterol 2021 Aug 9:101785. Epub 2021 Aug 9.

AP-HP Sorbonne Université, Hôpital Universitaire Pitié Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.clinre.2021.101785DOI Listing
August 2021

ATP-binding cassette transporters expression in rats with cirrhosis and hepatic encephalopathy.

Clin Res Hepatol Gastroenterol 2021 Aug 9:101784. Epub 2021 Aug 9.

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière study group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France.

Background: Pathophysiology of acute encephalopathy in cirrhotic patients is not completely understood. Factors implicated include ammonia, inflammation, various metabolic disorders and drug toxicity. Recent studies have evidenced an increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy, either to solutes, or to leukocytes. A modification of the expression of BBB ATP-Binding Cassette (ABC) transporters, actively transporting endogenous and exogenous components through the BBB, has been described in models of acute liver failure. We hypothesized that a modification of ABC transporters expression may contribute to drug-induced acute encephalopathy in cirrhosis.

Materiel And Methods: A rat model of cirrhosis induced by Bile Duct Ligation (BDL) was studied, and compared to a SHAM rat model. Rats were sacrificed and brains studied after decapitation. Genic expression of ABC transporters, including P-gp, BCRP, MRP1, MRP2, MRP4 and MRP5 was evaluated by RT-qPCR on isolated brain microvessels. Encephalopathy was assessed 6 weeks after surgery by a trail suspension test and an Open Field Test.

Results: BDL rats developed a histologically proven cirrhosis and displayed a higher ammonemia than SHAM rats (183 µmol/L vs 53 µmol/L, p=0.0003). BDL rats presented with encephalopathy shown by neurobehavioral tests. MRP2 was not detected neither in BDL nor in SHAM rats. There was a decrease in the genic expression of MRP5 6 weeks after surgery. Expressions of P-gp, BCRP, MRP1 and MRP4 were not different between the 2 groups.

Conclusion: We suggest that acute encephalopathy in cirrhotic BDL rats may be associated to a modification of ABC transporter MRP5 on the BBB, that could be responsible for a decrease clearance of neurotoxic agents.
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http://dx.doi.org/10.1016/j.clinre.2021.101784DOI Listing
August 2021

Letter to the Editor: Salvage TIPS in Patients With Cirrhosis With Variceal Bleeding: MELD, Lactates, and "à la Carte" Decision.

Hepatology 2021 Aug 5. Epub 2021 Aug 5.

Service d'Hépato-gastro-entérologie, Hôpital de la Pitié-Salpétrière, Hôpitaux Universitaires Pitié-Salpétrière-Charles Foix, Assistance-publique Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1002/hep.32091DOI Listing
August 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF PORTAL HYPERTENSION.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101767. Epub 2021 Jul 28.

Service d'hépatologie, Hôpital Rangueil, CHU Toulouse, Toulouse.

Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) ≥10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM <10 kPa, or Fibrotest® ≤0.58, or Fibrometer® ≤0.786. Patients with chronic liver disease (excluding vascular diseases) with a LSM <10 kPa are at low risk of developing portal hypertension complications. The presence of CSPH can be strongly suspected when LSM is ≥20 kPa. In a patient without clinical, endoscopic or radiological features of portal hypertension, measurement of the HVPG is recommended before major liver or intra-abdominal surgery, before extra-hepatic transplantation and in patients with unexplained ascites. Endoscopic screening for oesophageal varices can be avoided in patients with LSM <20 kPa and a platelet count >150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness ≥20 kPa or platelet count ≤50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.
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http://dx.doi.org/10.1016/j.clinre.2021.101767DOI Listing
July 2021

Poor Antibody Response after Two Doses of SARS-CoV-2 vaccine in Transplant Recipients.

Clin Infect Dis 2021 Jun 24. Epub 2021 Jun 24.

Sorbonne Université, Unité médicale de transplantation hépatique, AP-HP, Hôpital Pitié-Salpêtrière, 75013, Paris France.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant-recipients without previous COVID-19. No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the two doses. Our data suggests to change the vaccine strategy.
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http://dx.doi.org/10.1093/cid/ciab580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384412PMC
June 2021

External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV.

JHEP Rep 2021 Aug 24;3(4):100298. Epub 2021 Apr 24.

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.

Background & Aims: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals.

Methods: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France. LCR1-LCR2 was assessed retrospectively in patients with the test components and AFP, available at baseline. The co-primary study outcome was the negative predictive value (NPV) of LCR1-LCR2 for the occurrence of HCC at 5 years and for survival without HCC according to the predetermined LCR1-LCR2 cut-offs. The cut-offs were adjusted for risk covariables and for the response to HCV treatment, and were quantified using time-dependent proportional hazards models.

Results: In total, 4,903 patients, 1,026 (21.9%) with baseline cirrhosis, were included in the study. Patients were followed for a median of 5.7 (IQR 4.2-11.3) years. A total of 3,788/4,903 (77.3%) patients had a sustained virological response. There were 137 cases of HCC at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with low-risk LCR1-LCR2 compared with 113/1,148 patients with high-risk LCR1-LCR2. The NPV was 99.4% (95% CI 99.1-99.6). Similar findings (hazard ratio, 10.8; 95% CI, 8.1-14.3; <0.001) were obtained after adjustment for exposure to antivirals, age, sex, geographical origin, HCV genotype 3, alcohol consumption, and type 2 diabetes mellitus.

Conclusions: The results showed that LCR1-LCR2 can be used to successfully identify patients with HCV at very low risk of HCC at 5 years.

Lay Summary: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.

Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT01953458).
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http://dx.doi.org/10.1016/j.jhepr.2021.100298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187244PMC
August 2021

TIPS and liver transplantation should always be discussed together.

J Hepatol 2021 Oct 27;75(4):1000-1001. Epub 2021 May 27.

AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.

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http://dx.doi.org/10.1016/j.jhep.2021.05.012DOI Listing
October 2021

Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses….

Liver Int 2021 08 28;41(8):1734-1743. Epub 2021 Jun 28.

Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.

Background And Aims: Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients.

Methods: Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021.

Results: Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available.

Conslusions: Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.
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http://dx.doi.org/10.1111/liv.14977DOI Listing
August 2021

Combination of Model for End-Stage Liver Disease and Lactate Predicts Death in Patients Treated With Salvage Transjugular Intrahepatic Portosystemic Shunt for Refractory Variceal Bleeding.

Hepatology 2021 Oct 19;74(4):2085-2101. Epub 2021 Jul 19.

Service d'hépato-gastroentérologie et de nutrition, CHU Côte de Nacre, Caen, France.

Background And Aims: Data about the prognosis of salvage transjugular intrahepatic portosystemic shunt (TIPS) using covered stents for refractory variceal bleeding caused by portal hypertension are scarce. We aimed to assess survival and to identify predictors of mortality in these patients.

Approach And Results: One hundred sixty-four patients with cirrhosis from five centers treated with salvage TIPS between 2007 and 2017 were retrospectively divided into a derivation cohort (83 patients) and a validation cohort (81 patients). Comparisons were performed using the Mann-Whitney and Fischer's exact test. Six-week overall survival (OS) was correlated with variables on the day of the TIPS using Kaplan-Meier curves with log-rank test and univariate/multivariate analyses using the Cox model. Eighty-three patients were included in the derivation cohort (male, 78%; age, 55 years, alcohol-associated cirrhosis, 88%; Model for End-Stage Liver Disease [MELD], 19 [15-27]; arterial lactate, 3.7 mmol/L [2.0-8.3]). Six-week OS rate was 58%. At multivariate analysis, the MELD score (OR, 1.064; 95% CI, 1.005-1.126; P = 0.028) and arterial lactate (OR, 1.063; 95% CI, 1.013-1.114; P = 0.032) were associated with 6-week OS. Six-week OS rates were 100% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 5% in patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. The 81 patients of the validation cohort had similar MELD and arterial lactate level but lower creatinine level (94 vs 106 µmol/L, P = 0.008); 6-week OS was 67%. Six-week OS rates were 86% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 10% for patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. In the overall cohort, rebleeding rate was 15.8% at 6 weeks, and the acute-on-chronic liver failure grade (OR, 1.699; 95% CI, 1.056-1.663; P = 0.040) was independently associated with rebleeding.

Conclusions: After salvage TIPS, 6-week mortality remains high and can be predicted by MELD score and lactate. Survival rate at 6 weeks was >85% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15, while mortality was >90% for lactate ≥12 mmol/L and/or MELD score ≥ 30.
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http://dx.doi.org/10.1002/hep.31913DOI Listing
October 2021

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

Clin Res Hepatol Gastroenterol 2021 Apr 27;45(5):101713. Epub 2021 Apr 27.

Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France.

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 (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.170.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 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.
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http://dx.doi.org/10.1016/j.clinre.2021.101713DOI Listing
April 2021

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

J Hepatol 2021 Aug 12;75(2):342-350. Epub 2021 Jun 12.

Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.

Background & Aims: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.

Methods: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.

Results: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9).

Conclusion: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Lay Summary: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
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http://dx.doi.org/10.1016/j.jhep.2021.03.026DOI Listing
August 2021

Diagnosis and Management of Hepatic Encephalopathy.

Clin Liver Dis 2021 05 11;25(2):393-417. Epub 2021 Mar 11.

Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France. Electronic address:

Hepatic encephalopathy (HE) is a severe complication of cirrhosis. The prevalence of overt HE (OHE) ranges from 30% to 45%, whereas the prevalence of minimal HE (MHE) is as high as 85% in some case series. Widespread use of transjugular intrahepatic portosystemic shunt to control complications related to portal hypertension is associated with an increase in HE incidence. If the diagnosis of OHE remains simple in most cases, then the diagnosis of MHE is less codified because of many differential diagnoses with different therapeutic implications. This review analyzes current knowledge about the pathophysiology, diagnosis, and different therapeutic options of HE.
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http://dx.doi.org/10.1016/j.cld.2021.01.008DOI Listing
May 2021

Prognosis of patients undergoing salvage TIPS is still poor in the preemptive TIPS era.

Clin Res Hepatol Gastroenterol 2021 Mar 2;45(6):101593. Epub 2021 Mar 2.

Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France. Electronic address:

Background: Salvage transjugular intrahepatic portosystemic shunts (TIPS) are associated with poor prognosis, especially in patients with Child-Pugh C cirrhosis. Since preemptive TIPS improved prophylaxis of variceal bleeding in those patients, recourse to salvage TIPS may now affect patients with a better prognosis.

Aim: To assess the impact of the preemptive TIPS policy on outcomes after salvage TIPS placement.

Methods: We conducted a retrospective monocentric study on cirrhotic patients undergoing salvage TIPS with polytetrafluoroethylene-covered stents from 2002 to 2017 (period 1 until February 2011; period 2 after the preemptive TIPS policy in March 2011). The primary endpoint was one-year transplant-free survival.

Results: We included 106 patients (period 1/2 = 53/53 patients, male gender 82%, age 54 ± 9 years, alcoholic cirrhosis 70%, Child-Pugh score B/C 94%). One-year transplant-free survival was 46.0% during period 1 compared to 40.2% during period 2 (p = 0.65). Amongst 61 patients with history of variceal bleeding, 32 (52.5%) had an inadequate secondary prophylaxis, including 19 (59.4%) with a previous indication of preemptive TIPS. One-year transplant-free survival was 33.2% if inadequate secondary prophylaxis vs 65.2% if adequate (p = 0.008). Independent factors associated with survival were a lower Child-Pugh or MELD score, infection, failure to control bleeding, and hepatic encephalopathy after TIPS.

Conclusion: Prognosis after salvage TIPS remained poor in our series. Optimizing secondary prophylaxis, including preemptive TIPS placement, should be the main concern to improve prognosis.
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http://dx.doi.org/10.1016/j.clinre.2020.101593DOI Listing
March 2021

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

Ann Intern Med 2021 05 2;174(5):633-640. Epub 2021 Feb 2.

University Hospital of Toulouse and Toulouse III Paul Sabatier University, Toulouse, France (C.B., J.M.P., J.P.V.).

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 ( = 93) and 53% (CI, 43% to 63%) in the placebo group ( = 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.
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http://dx.doi.org/10.7326/M20-0202DOI Listing
May 2021

Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

World J Hepatol 2020 Dec;12(12):1326-1340

Department of Hepato-Gastroenterology, Claude Huriez University Hospital, Lille 59037, France.

Background: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use.

Aim: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated untreated hepatitis B virus (HBV)-monoinfected patients.

Methods: A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors.

Results: Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% 30.7%, 0.42 and 50.0% 30.7%, = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group the naïve group (hazard ratio: 2.283, = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo.

Conclusion: The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
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http://dx.doi.org/10.4254/wjh.v12.i12.1326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772739PMC
December 2020

Colonic tuberculosis as a cause of massive intestinal bleeding.

Clin Res Hepatol Gastroenterol 2021 01 6;45(1):101365. Epub 2021 Jan 6.

AP-HP, Groupe Hospitalier Pitié-Salpêtrière-Charles-Foix, Service d'hépato-gastro-entérologie, Sorbonne Universités, UPMC Université Paris 06, 47, boulevard de l'Hôpital, 75013 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.clinre.2019.12.011DOI Listing
January 2021

Performance of serum apolipoprotein-A1 as a sentinel of Covid-19.

PLoS One 2020 20;15(11):e0242306. Epub 2020 Nov 20.

Department of Internal Medicine and Clinical Immunology, Sorbonne Université, AP-HP Pitié-Salpêtrière, Paris, France.

Background: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.

Methods: We compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.

Results: The mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04).

Conclusion: Apolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242306PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679025PMC
December 2020

Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial.

Clin Gastroenterol Hepatol 2020 Oct 16. Epub 2020 Oct 16.

Department of Medicine, Virginia Commonwealth University, McGuire VA Medical Center, Richmond, Virginia.

Background & Aims: Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE.

Methods: We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution's standard of care (eg, lactulose to achieve 2-3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory).

Results: Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory-confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552).

Conclusions: In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419.
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http://dx.doi.org/10.1016/j.cgh.2020.10.019DOI Listing
October 2020

Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data.

Gastroenterology 2021 01 24;160(1):193-205.e10. Epub 2020 Sep 24.

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. Electronic address:

Background & Aims: Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS.

Methods: We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients.

Results: Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323-0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307-0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253-0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy.

Conclusions: In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.
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http://dx.doi.org/10.1053/j.gastro.2020.09.026DOI Listing
January 2021

Transjugular intrahepatic portosystemic shunt in patients with cirrhosis: Indications and posttransjugular intrahepatic portosystemic shunt complications in 2020.

United European Gastroenterol J 2021 Mar 23;9(2):203-208. Epub 2021 Feb 23.

Hepatology Intensive Care Unit, Pitie-Salpêtrière Hospital, Paris, France.

Transjugular intrahepatic portosystemic shunt is a percutaneous radiologic-guided procedure that aims to reduce portal hypertension by creating a shunt between the portal venous system and the hepatic venous system. The most common cause of portal hypertension is liver cirrhosis in Western countries. Two main indications of transjugular intrahepatic portosystemic shunt are validated by randomised controlled studies in patients with cirrhosis and variceal bleeding (salvage transjugular intrahepatic portosystemic shunt, early transjugular intrahepatic portosystemic shunt or rebleeding despite an optimal secondary prophylaxis) or refractory ascites. Careful selection of the patients is crucial in order to prevent posttransjugular intrahepatic portosystemic shunt complications, including liver failure, posttransjugular intrahepatic portosystemic shunt encephalopathy occurrence and cardiac decompensation, for a better long-term outcome. In this review, we will discuss transjugular intrahepatic portosystemic shunt indications in 2020 in patients with cirrhosis and portal hypertension, with a special focus on variceal bleeding and refractory ascites. Then, we will describe transjugular intrahepatic portosystemic shunt-related complications, the contraindications and the current knowledge on patient's selection.
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http://dx.doi.org/10.1177/2050640620952637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259430PMC
March 2021

Drastic decrease of urgent endoscopies outside regular working hours during the Covid-19 pandemic in the paris area.

Clin Res Hepatol Gastroenterol 2020 09 4;44(4):579-585. Epub 2020 Aug 4.

Sorbonne Université, Endoscopy Unit, AP-HP, Hôpital Saint-Antoine, 75012 Paris, France.

Background And Study Aims: The coronavirus 2019 (COVID-19) pandemic has significantly affected medical care. We surmise that the number of urgent endoscopies outside regular working hours in the Paris area decreased as a result. The objective of this study was to describe the observed number of acts during the 2020 mandatory period of home isolation, compared to the values in prior years and the expected value for 2020.

Material And Methods: We performed a multicenter cohort study to investigate the practice of urgent endoscopy acts, outside regular working hours, in Paris and its surrounding suburbs, in the setting of the COVID-19 pandemic. We collected the number of endoscopies performed between January 17th and April 17th 2018, 2019 and 2020. We then collected clinical, endoscopic and outcome variables from the patients of years 2019 and 2020.

Results: From March 17th to April 17th (during home isolation), the number of acts was respectively of 147 in 2018, 137 in 2019, and 79 in 2020, lower that the expected number of 142 (-44.0%). In 2020, the number of endoscopies for suspected gastrointestinal bleeding (GIB), and findings of variceal and non-variceal bleeding decreased by 52.1%, 69.2% and 43.1% respectively, after a month of home isolation. In-hospital death rate were similar.

Conclusions: This study confirms that the urgent endoscopy caseload outside regular hours decreased nearly by half during the pandemic. Our results suggest a decreased number of endoscopies for suspected gastrointestinal bleeding, and findings of variceal and non-variceal bleeding.
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http://dx.doi.org/10.1016/j.clinre.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402205PMC
September 2020

Transportation and handling of blood samples prior to ammonia measurement in the real life of a large university hospital.

Clin Chim Acta 2020 Nov 28;510:522-530. Epub 2020 Jul 28.

APHP Sorbonne University, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Pitié-Salpêtrière-Charles Foix Hospital Group, Hepatogastroenterology Department, Hepatogastroenterology Intensive Care Unit, Paris, France.

Background: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results.

Aims And Methods: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer. In the same routine context, the effects of waiting times of centrifuged samples or after plasma storage at -20 °C and -80 °C were determined.

Results: Despite the pneumatic transport, the lead times for sample arrival to the lab were even longer than those recommended for their complete handling until ammonia assay. Ammonia concentration results were not affected by the pneumatic transport of blood samples and by waiting times up to a maximum of 1.75 h before their centrifugation and 1 h after centrifugation. Ammonia stability was superior when plasma was stored at -80 °C.

Conclusion: Pneumatic transport and sample handling in the routine practice of our lab do not affect ammonia concentration results provided that waiting times are limited to 1.75 h before and 1 h after centrifugation and samples are kept cold. Otherwise, it is better to freeze plasma at -80 °C.
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http://dx.doi.org/10.1016/j.cca.2020.07.048DOI Listing
November 2020

Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus.

Am J Gastroenterol 2020 07;115(7):989-1002

Department of Medicine, University of Padova, Padova, Italy.

Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.
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http://dx.doi.org/10.14309/ajg.0000000000000603DOI Listing
July 2020

Personalized surveillance for hepatocellular carcinoma in cirrhosis - using machine learning adapted to HCV status.

J Hepatol 2020 12 29;73(6):1434-1445. Epub 2020 Jun 29.

AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris.

Background & Aims: Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status.

Methods: Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014).

Results: Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF].

Conclusions: Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs.

Lay Summary: Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.
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http://dx.doi.org/10.1016/j.jhep.2020.05.052DOI Listing
December 2020

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

J Hepatol 2020 11 24;73(5):1082-1091. Epub 2020 Apr 24.

Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.

Background & Aims: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date.

Methods: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality.

Results: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not.

Conclusions: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB.

Lay Summary: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
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http://dx.doi.org/10.1016/j.jhep.2020.04.024DOI Listing
November 2020

Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France.

Dig Dis Sci 2021 03 18;66(3):881-898. Epub 2020 Apr 18.

Département D'Hépatologie, Inserm U1223, Hôpital Cochin AP-HP, 27, rue du Faubourg Saint Jacques, 75014, Paris, France.

Background: Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations.

Aims: To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France.

Methods: This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy).

Results: Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy.

Conclusions: Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.
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http://dx.doi.org/10.1007/s10620-020-06234-1DOI Listing
March 2021

Optimal management of ascites.

Liver Int 2020 02;40 Suppl 1:128-135

Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, Paris, France.

Ascites is the most common complication of cirrhosis, which develops in 5%-10% of patients per year. Its management is based on symptomatic measures including restriction of sodium intake, diuretics and paracentesis. Underlying liver disease must always be treated and may improve ascites. In some patients, ascites is not controlled by medical therapies and has a major impact on quality of life and survival. TIPS placement and liver transplantation must therefore be discussed. More recently, repeated albumin infusions and Alfapump have emerged as new therapies in ascites. In this review, the current data on these different options are analysed and an algorithm to help the physician make clinical decisions is suggested.
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http://dx.doi.org/10.1111/liv.14361DOI Listing
February 2020

Parvovirus B19 infection: A challenging cause of fulminant hepatitis.

Clin Res Hepatol Gastroenterol 2020 09 6;44(4):e89-e91. Epub 2020 Jan 6.

Paul Brousse Hospital, 12, avenue Paul-Vaillant Couturier, 94800 Villejuif, France.

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http://dx.doi.org/10.1016/j.clinre.2019.12.004DOI Listing
September 2020
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