Philippe Mathurin's research while affiliated with Centre Hospitalier Universitaire de Nancy and other places
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Publications (423)
PurposeHepatitis C virus (HCV) cure after treatment with direct-acting antivirals (DAAs) can improve health-related quality of life (HRQoL). However, specific groups with chronic HCV may still exhibit worse post-cure HRQoL because of persisting severe liver fibrosis or social vulnerability factors (e.g. unhealthy alcohol use, living in poverty). We...
Background and objectives:
Hepatocellular carcinoma epidemiological data are limited in France. The Epidemio Liver Immunotherapy Tecentriq outcome research (ELITor) retrospective study, based on real-world data from the Carcinome HépatocellulaIrE en France (CHIEF) French cohort of hepatocellular carcinoma patients, aimed to get insight into the tr...
Background & aims:
Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for treating pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase 3 REGENERATE trial of OCA for treatment of NASH with a...
In patients with severe acute alcohol-related hepatitis not responding to medical therapy, early liver transplantation (LT) represents the only effective therapy and, when performed within strict and well-defined protocols, it is associated with a clear survival benefit and acceptable rates of return to alcohol use after transplantation. However, t...
Importance:
The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.
Objective:
To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.
Design, setting, and...
Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), and clock disruption increases susceptibility to non-alcoholic fatty liver disease (NAFLD) progression in ro...
Background and Aims: Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). In this context, hepatocyte dedifferentiation gives rise to cells with a hepatobiliary (HB) phenotype expressing biliary and hepatocytes markers and showing immature features. However, the mechanisms and the impact of hepat...
Background & aims:
Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical...
Background and aims:
Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). In this context, hepatocyte dedifferentiation gives rise to cells with a hepatobiliary (HB) phenotype expressing biliary and hepatocytes markers and showing immature features. However, the mechanisms and the impact of hepa...
Background & aims:
The aim of this analysis was to describe the nationwide distribution of patients with newly diagnosed Hepatocellular carcinoma (HCC) according to treatment pattern, aetiologies, and outcomes in France.
Method:
A retrospective cohort of patients with newly diagnosed HCC was selected over the period 2015-2017 in a French claims...
Background. The prognosis of patients with hepatocellular carcinoma (HCC) not eligible to curative treatment is poor. Little information is available on treatment modalities and outcomes of these patients in everyday practice. The aim of this analysis was to describe the characteristics of patients with a newly diagnosed intermediate, advanced, or...
Alcohol-associated liver disease (ALD) is the most common cause of cirrhosis and liver-related mortality in many regions worldwide. Around 75% of patients with cirrhosis are unaware of their disease until they are referred to the emergency rooms. An innovative non-invasive, screening approach is required for an earlier diagnosis of liver fibrosis....
Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical...
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: 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: Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with HCV chr...
Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death...
Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analys...
To validate cancer screening programs, experts recommend estimating effects on case fatality rates (CFRs) and cancer‐specific mortality. This study evaluates hepatocellular carcinoma (HCC) screening in patients with cirrhosis for those outcomes using a modeling approach. We designed a Markov model to assess 10‐year HCC‐CFR, HCC‐related, and overall...
Alcohol-related liver disease (ARLD) remains one of the leading causes of chronic liver disease and the prevalence of alcohol-related cirrhosis is still increasing worldwide. Thus, ARLD is one of the leading indications for liver transplantation worldwide especially after the arrival of direct-acting antivirals for chronic hepatitis C infection. De...
Background:
Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, th...
Background
The relationship between the severity of NAFLD and extra-hepatic events such as cardiovascular disease (CVD), extra-hepatic cancer (EHC) or chronic kidney diseases (CKD) has not been clearly investigated in the general population.
Aims
The aim of this study was to assess whether the severity of fibrosis in NAFLD subjects was associated...
Background and Aims
The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of...
Background
Opioid Agonist Treatments (OAT), i.e., methadone and buprenorphine, are key elements in the treatment of opioid addiction. Moreover, they help foster healthcare behaviors and reduce medical harm in people who use opioid drugs (PWUD). Here, aimed to explore whether the percentage of time on OAT (pOAT) among PWUD with hepatitis C virus (HC...
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...
Liver transplant (LT) candidates with a body mass index (BMI) over 40 kg/m2 have lower access to a liver graft without clear explanation. Thus, we studied the impact of obesity on the waiting list (WL) and aimed to explore graft proposals and refusal.
Method:
Data between January 2007 and December 2017 were extracted from the French prospective n...
Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal manageme...
Background:
The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but non-alcoholic fatty liver disease (NAFLD) has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects.
Method:
The study population consisted of participants from the F...
Background and aims:
Severe alcohol-related hepatitis (AH) is associated with an increased risk of infection, but the impact of pneumonia has not been specifically analyzed in a specific cohort.
Method:
All patients admitted for severe AH between 2002 and 2020 were prospectively included. Systematic screening for infection was performed at admis...
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 & Aims
After hepatitis C virus (HCV) cure, not all patients achieve significant liver fibrosis regression. We explored the effects of clinical and socio-behavioral factors on liver fibrosis, before and after HCV cure with direct-acting antivirals.
Methods
We analyzed data from the ongoing ANRS CO22 HEPATHER cohort, which prospectively c...
Severe form of alcoholic hepatitis (AH) defined by Maddrey’s discriminant function as equal to or higher than 32 is associated with a high mortality risk disease of around 20–30% at 1 month. For patients with severe alcoholic hepatitis, European and American clinical guidelines recommend corticosteroids in the absence of contraindications to reduce...
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:
Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe A...
Abstract Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods...
Background:
The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting.
Method:
This study inclu...
Background and aims
Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients.
Methods
We used 2 prospective cohorts of Child-Pugh A cirrhosis due either to alcohol or viral hepatitis. Primary end...
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
Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase 1–2 CheckMate 040 study. We aimed to investigate nivolumab monotherapy compared with sorafenib monotherapy in the first-line setting for patients with advanced hepatocellular carcinoma...
In Reply We do not agree with the claim by Drs Conteh and Levin that the legend in Figure 1 in our recent Review¹ was mischaracterized. We and others have shown that portal fibrosis is frequently observed in patients with alcohol-associated liver disease.²,3 Furthermore, unlike centrilobular fibrosis, portal fibrosis is highly correlated with fibro...
Background and aims
Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. The aim of this study was to evaluate the cost-effectiveness of MRI for the detection of very early HCC (BCLC 0) in patients with an annual HCC risk>3%.
Methods...
Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are availabl...
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 & Aims
Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioral correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We i...
Objectives
HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfectio...
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),...
Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH...
Background
In HCV-infected patients with advanced liver disease, the direct antiviral agents (DAAS)-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with DAAs from the French ANRS CO22 HEPATHER cohort.
Methods
We identified HCV pa...
Importance
Alcohol-associated liver disease results in cirrhosis in approximately 10% to 20% of patients. In 2017, more than 2 million people had alcohol-associated cirrhosis in the US. Alcohol-associated liver disease is the primary cause of liver-related mortality and the leading indication for liver transplant, representing 40% to 50% of all liv...
Background
Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined as MELD score >20. However, there are patients who may be too sick to benefit from therapy.
Aim
To identify the range of MELD score within which steroids are effective treatment for AH.
Methods
Retrospective, international multi-center...
Background & Aims
Alcoholic hepatitis (AH) is a life-threatening disease with limited therapeutic options, because understanding of the molecular drivers leading to death are not well understood. This study evaluates the Hippo/Yes-associated protein (YAP) pathway which has been shown to play a role in liver regeneration.
Method
The Hippo/YAP pathw...
Background and aims:
AUDIT-10 and its shorter form, AUDIT-C, are questionnaires used to characterize severity of drinking. We hypothesized that liver injury and short-term outcomes of alcohol-associated hepatitis (AH) would correlate with a patient's recent alcohol consumption as determined by AUDIT-10 and -C.
Methods:
We analyzed a prospective...
BACKGROUND AND AIM
Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised.
METHODS
Some of us recently described the histological presentation of hepatitis E in a large pa...
In patients with severe alcoholic hepatitis not responding to medical therapy, it is detrimental to postpone the decision to list a patient in this context of therapeutic dead end. The last decade has seen the place of early transplantation in the therapeutic arsenal in patients with severe alcoholic hepatitis using a restricted selection process o...
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 exp...
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...
We disagree with the conclusion of Vojjala et al., which states that clinicians should pay attention to metabolic risk factors, fatty liver and concurrent drug use. The authors questioned the presence of NAFLD in our study. However, the median BMI was normal in the patients admitted with ALITD and was not different from that of patients admitted wi...
Background
Serum transferrin levels represent an independent predictor of mortality in patients with liver failure. Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of hepatocyte functions. The aim of this study was to explore whether serum transferrin reflects HNF4α activity.
Methods
Factors regulating transferrin expression in alc...
Background & aims
In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.
Methods
This was a retr...
288
Background: The prognosis for patients with late-stage hepatocellular carcinoma (HCC) is poor, with only one systemic treatment option available for patients until 2017. Aim: To describe treatment patterns and survival of French patients following diagnosis of late-stage HCC (Barcelona Clinic Liver Cancer classification B, C or D), using a comp...
284
Background: Despite the screening of patients at risk, hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage disease, with a very poor prognosis. Aim: To describe risk factors, treatment patterns and survival of patients with newly diagnosed HCC in France over the period 2015-2017 using SNDS, the national administrative healthc...
