Publications by authors named "Levrero M"

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non-tumoural tissues (NTT).

Methods: A non-targeted metabolomic strategy LC-MS was applied to 52 pairs of human MASLD-HCC and NTT separated into 2 groups according to fibrosis severity F0F1-F2 versus F3F4.

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Background And Aim: Serum HBV RNA and HBcrAg levels have been proposed as useful biomarkers in the management of HBV patients, however their role in chronic hepatitis Delta (CHD) is currently unknown.

Methods: Consecutive untreated CHD patients were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected.

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Article Synopsis
  • The liver contains diverse populations of monocytes and macrophages, including liver-resident macrophages called Kupffer cells (KCs).
  • This text outlines a protocol for isolating KCs from human liver tissue removed during surgeries, detailing steps for tissue dissociation and cell separation.
  • It also includes instructions for validating the isolation process through immunofluorescence to confirm the presence of KCs by detecting the CD163 marker.
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Background & Aims: Circulating HBV RNAs have been proposed as a biomarker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA) and may help to evaluate HBV treatment activity. Different research assays have been proposed and, although two PCR-based research use only investigational assays have been developed, the lack of standardized protocols represents an important limitation. Here we have designed and generated a stable clonal cell line producing an RNA-based standard for the calibration of PCR-based circulating HBV RNA assays.

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Background & Aims: Although most hepatocellular carcinoma (HCC) cases are driven by hepatitis and cirrhosis, a subset of patients with chronic hepatitis B develop HCC in the absence of advanced liver disease, indicating the oncogenic potential of hepatitis B virus (HBV). We investigated the role of HBV transcripts and proteins on HCC development in the absence of inflammation in HBV-transgenic mice.

Methods: HBV-transgenic mice replicating HBV and expressing all HBV proteins from a single integrated 1.

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Gene therapy for hemophilia is a groundbreaking treatment approach with promising results and potential to reduce the burden of the disease. However, uncertainties remain, particularly regarding the liver side effects of AAV gene therapy, which are more common in hemophilia A. Unlike some other diseases, such as spinal muscular atrophy, where the target cell for gene therapy is different from the one affected by side effects, hemophilia gene therapy operates within the same cellular domain-the hepatocyte.

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Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity. We aimed to assess the impact of obesity on the performance of different noninvasive tests, including liver stiffness measurement (LSM) and Agile3+ (A3+), to detect advanced fibrosis (AF) in a population of patients with MASLD encompassing a wide range of BMI values.

Methods: A total of 479 patients with MASLD were consecutively included (Lyon Hepatology Institute).

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Article Synopsis
  • - The study investigates how selgantolimod (SLGN), a toll-like receptor 8 agonist, affects immune cells in the liver to aid in curing chronic hepatitis B (CHB) through new therapy combinations.
  • - Researchers characterized the changes in liver immune cell activity and gene expression induced by SLGN, finding that it changes Kupffer cell (KC) markers and affects HBV virus entry into liver cells.
  • - The findings suggest that SLGN not only impacts existing HBV infections but also alters the immune environment in the liver, highlighting its potential as part of future treatment strategies for HBV.
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Background: We evaluated long-term trajectories of circulating hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study.

Methods: We included 29 persons with HIV with HBsAg loss and 29 matched persons with HIV without HBsAg loss. We compared HBV RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates.

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Background: Epigenetic mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, are highly involved in the regulation of hepatocyte viability, proliferation, and plasticity. We have previously demonstrated that repression of H3K27 methylation in differentiated hepatic HepaRG cells by treatment with GSK-J4, an inhibitor of JMJD3 and UTX H3K27 demethylase activity, changed their phenotype, inducing differentiated hepatocytes to proliferate. In addition to the epigenetic enzymatic role in the regulation of the retro-differentiation process, emerging evidence indicate that microRNAs (miRNAs) are involved in controlling hepatocyte proliferation during liver regeneration.

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Background & Aims: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC.

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Reduced expression of the RNA helicase DDX5 associated with increased hepatocellular carcinoma (HCC) tumor grade and poor patient survival following treatment with sorafenib. While immunotherapy is the first-line treatment for HCC, sorafenib and other multi-tyrosine kinase inhibitors (mTKIs) are widely used when immunotherapy is contra-indicated or fails. Herein, we elucidate the role of DDX5 in sensitizing HCC to sorafenib, offering new therapeutic strategies.

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Objective: A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg).

Design: Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients.

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Objectives: Improving the understanding of the patterns of quantitative hepatitis B surface antigen (qHBsAg) trajectories associated with HBsAg loss is important in light of novel anti-hepatitis B virus agents being developed. We evaluated long-term qHBsAg trajectories in persons with HIV and HBV during tenofovir-containing antiretroviral therapy in the Swiss HIV Cohort Study.

Methods: We included 29 participants with and 29 without HBsAg loss, defined as qHBsAg <0.

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Background & Aims: Finite duration of treatment associated with HBsAg loss is the current goal for improved therapeutic approaches against chronic HBV infection, as it indicates elimination or durable inactivation of intrahepatic covalently closed circular DNA (cccDNA). To assist drug development, the definition of early predictive markers of HBsAg loss by assessing their value in reflecting intrahepatic cccDNA levels and transcriptional activity is essential. Fine needle aspirates (FNAs) have recently emerged as a less invasive alternative to core liver biopsy (CLB) and showed to be useful for investigating intrahepatic immune responses.

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Bacterial infections are the most frequent precipitating event in patients with acute decompensation of cirrhosis (AD) and are associated with high mortality. Early diagnosis is challenging due to cirrhosis-related systemic inflammation. Here we investigated the potential of circulating microRNAs to diagnose bacterial infections and predict survival in cirrhotic patients with AD.

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Background: Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.

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Purpose: A systematic screening for the presence of nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis is currently recommended in patients with type 2 diabetes mellitus (T2DM) and obesity. However, real-world data of such liver fibrosis risk stratification pathway from diabetology and nutrition clinics towards hepatology clinics are scarce. Therefore, we compared data from two pathways with or without transient elastography (TE) performed in diabetology and nutrition clinics.

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Background & Aims: Prophylaxis with nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) has decreased the rate of HBV recurrence after orthotopic liver transplantation (OLT), but the duration of this prophylaxis remains debated. Our aim was to investigate the recurrence of both intrahepatic and serum HBV markers after OLT in patients receiving long-term NUC and HBIG prophylaxis.

Methods: A total of 31 HBV-positive patients benefiting from OLT were prospectively enrolled in five French centres between 2012 and 2015.

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Article Synopsis
  • * The TRIPLET-HCC trial is a phase II-III study that aims to evaluate the efficacy and safety of adding ipilimumab to the current double therapy of atezolizumab and bevacizumab for patients with specific types of HCC.
  • * The trial's primary goals are to compare the objective response rates and overall survival between the triple and double therapy groups, while also examining progression-free survival, patient tolerance, quality
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Objectives: A major goal of curative hepatitis B virus (HBV) treatments is the reduction or inactivation of intrahepatic viral covalently closed circular DNA (cccDNA). Hence, precise cccDNA quantification is essential in preclinical and clinical studies. Southern blot (SB) permits cccDNA visualisation but lacks sensitivity and is very laborious.

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