Publications by authors named "Charlotte Bouzbib"

13 Publications

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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

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF PRIMARY SCLEROSING CHOLANGITIS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101775. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux.

Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.
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http://dx.doi.org/10.1016/j.clinre.2021.101775DOI Listing
July 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF NON-ALCOHOLIC FATTY LIVER DISEASE.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101769. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac; INSERM U1053, Université de Bordeaux, Bordeaux.

NAFLD is a frequent disease that affects 25% of the worldwide population. There is no specific diagnostic test for NAFLD, and the diagnosis mainly relies on the elimination of the other causes of chronic liver diseases with liver biopsy kept for unsure diagnoses. Non-invasive tests are now available to assess NAFLD severity and therefore to help physicians decide on the patient management and follow-up. These non-invasive tests can also be used to define pathways that organize referrals from primary care and diabetology clinics to the liver specialist, with the ambition to improve the screening of asymptomatic patients with NAFLD and advanced liver disease. NAFLD being the liver expression of the metabolic syndrome, physicians need also take care to screen for diabetes and to evaluate the cardiovascular risk in those patients. These recommendations from the French Association for the Study of the Liver (AFEF) aim at providing guidance on the following questions: how to diagnose NAFLD; how non-invasive tests should be used to assess NAFLD severity; how to follow patients with NAFLD; when to perform liver biopsy in NAFLD; and how to decide referral to the liver specialist for a patient with NAFLD.
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http://dx.doi.org/10.1016/j.clinre.2021.101769DOI Listing
July 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

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF RARE GENETIC LIVER DISEASES.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101768. Epub 2021 Jul 28.

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

Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease, must be investigated in any patient with unexplained liver disease and/or unexplained neurological or neuropsychiatric disorders. The diagnosis is based on a combination of clinical, biological features, including copper balance. The exchangeable copper/total copper ratio is a new sensible and specific biological marker, useful for the diagnosis of the disease. Timely diagnosis and treatment will prevent serious complications from the disease. Neurological evaluation and familial screening are essential in patients with Wilson's disease.
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http://dx.doi.org/10.1016/j.clinre.2021.101768DOI Listing
July 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF AUTOIMMUNE HEPATITIS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101772. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille.

Autoimmune hepatitis (AIH) is a liver disease characterised by necrotico-inflammatory lesions of hepatocytes, the presence of specific autoantibodies and response to corticosteroid treatment. AIH must be considered in any patient with acute or chronic liver disease. As there is no pathognomonic sign of AIH, the diagnosis is based on a combination of clinical, biological, immunological and histological findings, after excluding other causes of liver disease. The clinical and biological presentation of AIH is variable and AIH can be associated with an autoimmune biliary disease, primary biliary cholangitis or primary sclerosing cholangitis in an overlap syndrome. For these reasons, diagnosis of AIH can be challenging. Even if liver histology remains essential in the diagnosis of AIH, non-invasive tests can be used at different steps of the management of AIH: diagnosis of AIH, notably diagnosis of an overlap syndrome, assessment of severity of AIH, searching for extra-hepatic disease frequently associated to AIH, evaluation of response to therapy, decision of treatment withdrawal. This review aims to provide practical guidelines for the use of non-invasive tests for the diagnosis and the follow-up of AIH.
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http://dx.doi.org/10.1016/j.clinre.2021.101772DOI Listing
July 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 May 21. Epub 2021 May 21.

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
May 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

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

Unsolved Questions in Salvage TIPSS: Practical Modalities for Placement, Alternative Therapeutics, and Long-Term Outcomes.

Can J Gastroenterol Hepatol 2019 1;2019:7956717. Epub 2019 Apr 1.

Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Charles Foix Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Salvage transjugular intrahepatic portosystemic shunt (TIPSS) has proven its efficacy to treat refractory variceal bleeding for patients with cirrhosis. However, this procedure is associated with very poor outcomes. As it is used as a last resort to treat a severe complication of cirrhosis, it seems essential to improve our practice, with the aim of optimizing management of those patients. Somehow, many questions are still unsolved: which stents should be used? Should a concomitant embolization be systematically considered? Is there any alternative therapeutic in case of recurrent bleeding despite TIPSS? What are the long-term outcomes on survival, liver transplantation, and hepatic encephalopathy after salvage TIPSS? Is this procedure futile in some patients? Is prognosis with salvage TIPSS nowadays as bad as earlier, despite the improvement of prophylaxis for variceal bleeding? The aim of this review is to summarize those data and to identify the lacking ones to guide further research on salvage TIPSS.
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http://dx.doi.org/10.1155/2019/7956717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463599PMC
August 2020

Altered distal-proximal temperature gradient as a possible explanation for sleep-wake disturbances in cirrhotic patients.

Liver Int 2017 12;37(12):1776-1779

Sorbonne Universités, Université Pierre et Marie Curie Paris 6, Paris, France.

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http://dx.doi.org/10.1111/liv.13590DOI Listing
December 2017

Bleeding from gastroduodenal metastases as the first manifestation of lung adenocarcinoma.

Endoscopy 2014 14;46 Suppl 1 UCTN:E474-5. Epub 2014 Oct 14.

Department of Gastroenterology and Hepatology, APHP Lariboisière Hospital, Paris, France.

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http://dx.doi.org/10.1055/s-0034-1377540DOI Listing
June 2015
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