Christophe Moreno

Université Libre de Bruxelles | ULB · Service de Gastro-Entérologie, d'Hépato-Pancréatologie et d'Oncologie Digestive - Hôpital Erasme

Introduction: In alcohol-associated cirrhosis, an accurate estimate of the risk of death is essential for patient care. We developed individualized prediction charts for 5-year liver-related mortality among outpatients with alcohol-associated cirrhosis that take into account the impact of abstinence. Methods: We collected data on outpatients wit...

Background and aims: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. Methods: A five-year prospective multi-cent...

Background & aims: Diabetes mellitus is a major risk factor for fatty liver disease development and progression. A novel machine learning method identified five clusters of patients with diabetes, with different characteristics and risk of diabetic complications using six clinical and biological variables. We evaluated whether this new classificat...

Background & aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among CLD patients of different etiologies and disease stages. Methods: 357 patients were recruited in clinical centers from 6 European cou...

Background & Aims Hepatitis E virus (HEV) genotype (gt) 3 infections are prevalent in high income countries and display a wide spectrum of clinical presentations. Host – but not viral – factors are reported to be associated with worse clinical outcomes. Methods Demographic, clinical and biochemical data of laboratory confirmed HEV infections (by P...

Background: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts. Methods: Information was obtained from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiol...

Background and aims This study aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine hepatocellular carcinoma (HCC) risk stratification. Methods Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt–β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in pa...

Background and aims The harmful impact of heavy alcohol recurrence has been confirmed in patients with alcohol-related cirrhosis although this is based on old studies. The drivers of long-term outcome still need to be clearly investigated. Method All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (2...

Background: Transjugular intrahepatic portosystemic shunt (TIPS) may be used as a salvage treatment in patients with cirrhosis and refractory variceal bleeding. Aim: To synthesize the available evidence on the efficacy of TIPS in patients with cirrhosis and refractory variceal bleeding. Methods: Meta-analysis of trials evaluating TIPS in patie...

In selected patients with cirrhosis and ascites, transjugular intrahepatic porto‐systemic shunt (TIPS) placement improves control of ascites and may reduce mortality. In this review, we summarize the current knowledge concerning the use of TIPS for the treatment of ascites in patients with cirrhosis, from pathophysiology of ascites formation to hem...

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Stud...

BACKGROUND & AIMS Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10...

Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We c...

Background & Aims Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with hepatitis C virus (HCV). Patients who fail therapy may select viruses with drug resistance-associated substitutions (RAS), limiting retreatment options and risking onward resistant virus transmission. SHARED is an international consortium of clinicians...

Objective Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. Design Two large cohorts of patients were recruited in an int...

Background Hepatocellular carcinoma is a frequent consequence of alcohol-related liver disease, with variable incidence among heavy drinkers. We did a genome-wide association study (GWAS) to identify common genetic variants for alcohol-related hepatocellular carcinoma. Methods We conducted a two-stage case-control GWAS in a discovery cohort of 210...

Background and study aims Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with limited treatment options. Duodenal mucosal resurfacing (DMR) has been associated with improvement in glycaemic parameters and liver function tests (LFTs) in type 2 diabetes. This study aimed to assess the effect of DMR in patien...

Background & Aims Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. Methods Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10...

Introduction: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (bas...

As already known, patients infected and successfully treated before initiation of corticosteroids have similar survival to non‐infected sAH; thus, there is no reason to delay sAH treatment after infection control. As stated in the manuscript, 42(30%) patients were already infected upon admission.

Background & Aims The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients. Methods SALVE grade was described by semiquantitative scores for steatosis...

Background & aims: Infection is a major driver of mortality in patients with advanced alcohol-related liver disease (ALD). The epidemiology and clinical course of infected patients with life-threatening forms of ALD, including severe alcoholic hepatitis (sAH) and decompensated alcoholic cirrhosis (DAC), and specific risk factors for infection rema...

Background & aims Severe alcoholic hepatitis (AH) is a highly lethal condition and it is still a challenge to predict the outcomes. We previously identified and validated a composite score of hepatic 123-gene prognostic signature and the MELD score, gene signature (gs)-MELD. However, a need for liver biopsy limits its clinical application. Therefor...

Background and Aims This study aimed to analyse the impact of the aetiology of underlying cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and two prospective cohorts of patients with compensated histologically proven...

Background and Aim The aim of this study is to describe the cholangiographic features and endoscopic management of biliary cast syndrome (BCS), a rare specific ischemic cholangiopathy following liver transplantation. Methods Patients with biliary complications were identified from prospectively collected database records of patients who underwent...

Background and aim The alcoholic hepatitis histologic score has been proposed as a new prognostic tool to assess the risk of death in alcoholic hepatitis. We aimed to evaluate its prognostic value in patients with severe alcoholic hepatitis. Methods Liver biopsies were analysed independently by two pathologists according to the alcoholic hepatitis...

Alcoholic hepatitis should be suspected in every patient with excessive chronic alcohol consumption and recent onset of jaundice. Diagnosis of alcoholic hepatitis is based on clinical and laboratory findings, and confirmed by a liver biopsy when available. Several scores are available to assess severity and prognosis of alcoholic hepatitis. The 1-m...

Introduction Current management of severe alcoholic hepatitis is based on corticosteroid therapy and abstinence from alcohol. As liver transplantation is lifesaving in alcoholic hepatitis patients at high risk of early death, refractory alcoholic hepatitis has become a new indication for liver transplantation in highly selected non-responders to co...

Background & aims: Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH. Methods: This is a meta-analysis of randomised controlled trials evaluating the risk of...

Data on the prevalence of resistance‐associated substitutions (RASs) and their implications for treatment with direct acting antivirals (DAAs) is sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4‐...

Background & Aims Severe forms of alcohol-related liver disease are associated with increased susceptibility to infections contributing to their poor prognosis. The cellular and molecular mechanisms responsible for this altered host defense are incompletely understood. Methods We performed whole blood phenotypic analysis and ex vivo stimulation wi...

Prescription and efficacy of daclatasvir and sofosbuvir ± ribavirin, including patient-reported outcomes, in routine practice in three European countries: the CMPASS-EU cohort study. Objectives: To identify patient characteristics associated with routine prescription of daclatasvir (DCV) in chronic hepatitis C virus (HCV) infection and evaluate eff...

Background: Alcohol-related liver disease (ALD) represents a major cause of death worldwide, and unfortunately, most patients are diagnosed at an advanced stage of the disease, which is related to poorer outcomes. Liver biopsy has historically been the gold standard for identifying advanced hepatic fibrosis, but this approach has several limitatio...

Background: Mitochondria play a fundamental role in the pathogenesis of Alcoholic Liver Disease (ALD). The preservation of functional mitochondria during toxic alcohol insults is essential for cell survival and is maintained by key processes known as mitochondrial dynamics, including fragmentation and fusion, which are regulated by mitochondria-sh...

Background and aims: Patients with alcoholic hepatitis and a modified Maddrey's discriminant function (mDF) <32 have a low risk of short-term mortality. However, few data exist concerning long-term outcomes. The aims of this study were to evaluate 5-year survival rates and to identify predictive factors for long-term prognosis in this patient popu...

Alcohol-related liver disease (ALD), which includes a range of disorders of different severity and is one of the most prevalent types of liver disease worldwide, has recently regained increased attention. Among other reasons, the realisation that any alcohol intake, regardless of type of beverage represents a health risk, and the new therapeutic st...

Purpose Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. Methods Patients were enrolled...

Background & aims: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze blood metabolome in patien...

Background: Few effective treatments are available for patients with cirrhosis and refractory ascites. New treatment modalities are needed for these patients. Aim: To synthesise the available evidence on the efficacy and safety of automated low-flow ascites pump therapy in patients with cirrhosis and refractory ascites. Methods: Electronic dat...

Background: The gene-signature-MELD (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH. Aim: To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH. Metho...

Background and Aims AGATE‐I Part I previously reported high sustained virologic response rates in hepatitis C genotype 4 patients with cirrhosis, with 12 and 16 weeks' treatment with a combination of two direct‐acting antivirals, ombitasvir and paritaprevir (codosed with ritonavir), plus ribavirin. Part II, reported here, extended the trial to incl...

Recently, a loss of function variant (rs72613567) in 17‐beta‐hydroxysteroid dehydrogenase 13 (HSD17B13) has been identified as protective of non‐alcoholic and alcoholic liver disease (ALD). However, the role of this SNP in the development of HCC is currently unknown. 3,315 European patients with HCC (n=1,109) or without HCC but with chronic liver d...

Figure S1. Comparison of efficacy of ombitasvir, paritaprevir, and ritonavir, plus ribavirin, in patients with hepatitis C virus genotype 4 infection and compensated cirrhosis in Parts I and II. Table: Adverse events and post‐baseline laboratory abnormalities (safety population)

Nucleos(t)ide Analogue withdrawal has been described to result in significant Hepatitis B surface antigen (HBsAg) loss rates in patients with long‐term viral suppression and negative HBeAg at the start of treatment. In these patients off‐treatment HBsAg loss is often preceded by viral rebound with concomitant Alanine Aminotransferase flares. In the...

Background The hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. Methods Full genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A and/or NS5B t...

The combination of 3 direct‐acting antiviral agents (AL‐335, odalasvir and simeprevirJNJ‐4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a Phase IIa study in chronic hepatitis C virus (HCV) genotype (GT)‐1‐infected patients without cirrhosis and has now been evaluated in a larger Phase IIb study, OMEGA‐1. This multicenter, r...

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation via the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current stu...

Few single nucleotide polymorphisms (SNPs) have been reproducibly associated with hepatocellular carcinoma (HCC). Our aim was to test the association between nine SNPs and HCC occurrence. SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B, STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3‐rs738409, TM6SF2‐rs58542926) in GWAS were genotyped in dis...

Background and aims: The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of hepatocellular carcinoma (HCC). Patients: With biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main end point was the incidence of HCC. Secondary outc...

Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bil...

Methods: Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicentre ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor +/- RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a SVR12. Results: Among the...

Background & aims: A better identification of factors predicting death is needed in alcoholic hepatitis. Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF, pACLF) or during follow-up (incidental ACLF, iACLF). This study analyzed the impact of ACLF on outcomes...

Background and aims: Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase 2 or 3 clinical trials, G/P achieved sustained virologic response 12 weeks post-treatment (SVR12) rates of 93-100% across all six major HCV genotypes (GT...

Background: Simeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union. Methods: This 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and...