Characterization of the Intrahepatic Inflammatory Microenvironment in Patients With Non-alcoholic Steatohepatitis

Condition(s) studied

Investigational drug(s) / intervention(s)

Liver Fine-Needle Aspiration: At the time of inclusion, when liver biopsy will be performed as part of routine medical management, fine-needle aspiration will also be made in all patients. The procedure will be performed in the Day Hospital, immediately after the liver biopsy.

Study summary

Non-alcoholic fatty liver disease (NAFLD) is a nosological entity that groups together non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Unlike NAFL, NASH is characterized by intrahepatic inflammation, and is solely at risk of progression to cirrhosis and hepatocellular carcinoma (HCC).

It is currently estimated that NAFLD affects approximately 25% of the world's adult population, and its incidence is rising in all regions of the world. Nevertheless, of all patients with NAFLD, only \~25% have NASH.

Identifying patients with NASH is therefore crucial, determining the need for follow-up to detect the onset of fibrosis and/or HCC, and eventual access to therapeutic trials. Furthermore, intrahepatic inflammation, the initial driver of NASH, appears to play an important role in the development of fibrosis and HCC, which can occur in the absence of cirrhosis in these patients. However, few studies have been carried out in humans to date, with data mainly coming from mouse models.

An innovative technique, Fine-Needle Aspiration (FNA), enables to obtain cells from the liver compartment, including large numbers of immune cells. In participants with NAFLD and indication of liver biopsy, a FNA will also be performed. Forty patients will be included, with \~75% of NASH and \~25% of NAFL expected. The investigators will study the phenotypic and functional characteristics of human intrahepatic inflammatory cells obtained by the FNA with different innovative techniques (RNAseq, multiparameter immunophenotyping, single-cell secretome and phosphoproteome). Peripheral Blood Mononuclear Cells and circulating microRNAs, known to regulate immune responses, will also be analysed.

The hypothesis of Profile-NASH is that intrahepatic inflammatory profiles differ between NASH and NAFL, and is associated with fibrosis progression and carcinogenesis.

This pilot study, based on high-definition technologies, will provide precise new insights into the quality of intrahepatic inflammation and the mechanisms favoring the transition from NAFL to NASH and its progression. Precise analysis of the intrahepatic inflammatory microenvironment will enable the investigators to identify new players in the pathogenesis of NASH, and potential future therapeutic targets.

Eligibility

Primary outcome measure(s)

• The primary endpoint is the comparison of transcriptomic profiles between NAFL and NASH patients. — At the time of the procedure liver biopsy at Day 1
  Cells collected from the RNA extraction plasma cell will be analyzed with technique: \- Transcriptomic analysis (RNA-Seq) The data obtained by these analyses will be compared between patients with NASH vs. NAFL, using multiple testing corrections.
• The primary endpoint is the secretome and single-cell phosphoproteome between NAFL and NASH patients. — At the time of the procedure liver biopsy at Day 1
  Cells collected from the FNA procedure will be analyzed with technique: \- Single-cell secretome and phosphoproteome by ISOPLEXIS® The data obtained by these analyses will be compared between patients with NASH vs. NAFL, using multiple testing corrections.
• The primary endpoint is the immunophenotyping of intrahepatic mononuclear cells between NAFL and NASH patients. — At the time of the procedure liver biopsy at Day 1
  Cells collected from the peripheral blood mononuclear cells will be analyzed with technique: \- Multiparameter immunophenotyping by spectral cytometry The data obtained by these analyses will be compared between patients with NASH vs. NAFL, using multiple testing corrections.

Trial sites (1)

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