Autoimmune Hepatitis, Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
autoimmune hepatitis, lipidomic analysis, extracellular vesicles, fatty acids, biomarkers, NAFLD
Brief summary
This is a two-arm, prospective, controlled observational pilot clinical study aimed at characterizing the lipidomic profile and extracellular vesicles (EVs) of patients with autoimmune hepatitis (AIH) compared to patients with non-alcoholic fatty liver disease (NAFLD). A total of 24 adult outpatients will be enrolled at the Hepatology Outpatient Unit of IRCCS "S. de Bellis". Blood samples will be collected by venipuncture to perform lipidomic analyses on red blood cell membranes and serum, and to isolate and characterize EVs. No intervention beyond standard clinical practice will be applied
Detailed description
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by high serum levels of transaminases and IgG immunoglobulins, presence of organ-specific and non-organ-specific autoantibodies, and interface hepatitis at histopathology. Two distinct types are recognized: AIH type 1, associated with anti-smooth muscle antibodies (SMA) and/or antinuclear antibodies (ANA); and AIH type 2, associated with anti-liver-kidney microsome type 1 (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC-1) antibodies. AIH presents a heterogeneous clinical picture driven by immune dysregulation involving B and T lymphocytes and macrophages. The autoimmune response is initiated by T lymphocyte recognition of self-antigens presented by MHC molecules, leading to differentiation into Th1, Th2, or Th17 cells that mediate hepatic damage. Extracellular vesicles (EVs) have recently been implicated in AIH pathogenesis, acting as mediators of intercellular communication. EVs can carry autoantigens, signaling molecules, lipids, and nucleic acids, modulating immune responses and potentially facilitating immune tolerance disruption. In AIH, EVs may vehicle hepatic autoantigens and modulate immune cell activity in the liver. No specific biomarkers currently exist that reliably distinguish AIH from other hepatic conditions, including NAFLD/MASLD, with which it is frequently associated due to overlapping metabolic alterations. A lipidomic approach is therefore proposed to identify specific lipid profiles associated with AIH. Lipidomic analysis will be performed on red blood cell membranes and serum of both study arms. Extracted fatty acids will be derivatized and analyzed by gas chromatography with flame ionization detection (GC-FID), compared against the FAME Mix-37 chromatogram. EVs isolated from serum will be further characterized for potential use as biocompatible nanovectors for immunosuppressive or immunomodulatory drug delivery.
Interventions
None listed
Sponsors
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ARM A: * Confirmed diagnosis of autoimmune hepatitis (AIH); * Adult age (≥18 years); * Ability to provide written informed consent; Attending the Hepatology Outpatient Unit of IRCCS "S. de Bellis" ARM B:
Exclusion criteria
* Confirmed diagnosis of non-alcoholic fatty liver disease (NAFLD); * Adult age (≥18 years); * Ability to provide written informed consent; Attending the Hepatology Outpatient Unit of IRCCS "S. de Bellis" Esclusion Criteria: * Liver cirrhosis; * Active oncological diseases; * Viral hepatitis (HBV, HCV, HIV infection); * Severe medical conditions that may compromise study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lipidomic profile | At enrollment (single time point - baseline blood draw) | Identification of specific lipid profiles (fatty acid composition) on red blood cell membranes and serum associated with AIH compared to NAFLD, assessed by gas chromatography with flame ionization detection (GC-FID). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and size distribution of serum-derived extracellular vesicles assessed by nanoparticle tracking analysis (NTA) | At enrollment (single time point - baseline blood draw) | Isolation and characterization of EVs from patient serum to evaluate their use as biocompatible nanovectors for immunosuppressive/immunomodulatory drug delivery |
| Concentration of serum lipidomic and biochemical biomarkers for AIH diagnosis assessed by integrated lipidomic and biochemical analysis | At enrollment (single time point - baseline blood draw) | Identification of molecular biomarkers for early and accurate AIH diagnosis through integrated lipidomic and biochemical analysis |
| Expression profile of EV-associated proteins and miRNAs involved in AIH pathogenesis assessed by proteomic and transcriptomic analysis | At enrollment (single time point - baseline blood draw) | Identification of molecular pathways involved in AIH pathogenesis through EV characterization |
Countries
Italy
Contacts
CONTACTMaria Notarnicola, biologyst
CONTACTValentina De Nunzio
Outcome results
None listed