Molecular Characterization of Autoimmune Hepatitis: A Lipidomic Approach (AIH-LIPID)
Molecular Characterization of Autoimmune Hepatitis Through Lipidomic Analysis and Extracellular Vesicle Profiling: A Controlled Pilot Clinical Study
Descripción general del estudio
Estado
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Maria Notarnicola, biologyst
- Número de teléfono: +39 0804994623
- Correo electrónico: maria.notarnicola@irccsdebellis.it
Copia de seguridad de contactos de estudio
- Nombre: Valentina De Nunzio
- Número de teléfono: +39 0804994623
- Correo electrónico: valentina.denunzio@irccsdebellis.it
Ubicaciones de estudio
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Bari
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Castellana Grotte, Bari, Italia, 70013
- IRCCS "S. de Bellis" - Nutritional Biochemistry Lab
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Contacto:
- Maria Notarnicola, Biologyst
- Número de teléfono: 0804994623
- Correo electrónico: maria.notarnicola@irccsdebellis.it
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Contacto:
- Valentina De Nunzio
- Número de teléfono: 0804994623
- Correo electrónico: valentina.denunzio@irccsdebellis.it
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Investigador principal:
- Maria Notarnicola
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Sub-Investigador:
- Emanuela Aloisio Caruso
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Sub-Investigador:
- Valentina De Nunzio
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Sub-Investigador:
- Giuliano Pinto
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Sub-Investigador:
- Angela Tafaro
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Sub-Investigador:
- Maria Principia Scavo
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Sub-Investigador:
- Raffaele Cozzolongo
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Sub-Investigador:
- Endrit Shahini
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Sub-Investigador:
- Pasqua Letizia Pesole
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Arm A - Autoimmune Hepatitis (AIH)
12 adult outpatients with a confirmed diagnosis of autoimmune hepatitis (AIH), attending the Hepatology Outpatient Unit (UOSD Epatopatie) of IRCCS "S. de Bellis".
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Arm B - Non-Alcoholic Fatty Liver Disease (NAFLD)
12 adult outpatients with a confirmed diagnosis of non-alcoholic fatty liver disease (NAFLD), attending the Hepatology Outpatient Unit (UOSD Epatopatie) of IRCCS "S. de Bellis".
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Lipidomic profile
Periodo de tiempo: At enrollment (single time point - baseline blood draw)
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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).
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At enrollment (single time point - baseline blood draw)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number and size distribution of serum-derived extracellular vesicles assessed by nanoparticle tracking analysis (NTA)
Periodo de tiempo: At enrollment (single time point - baseline blood draw)
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Isolation and characterization of EVs from patient serum to evaluate their use as biocompatible nanovectors for immunosuppressive/immunomodulatory drug delivery
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At enrollment (single time point - baseline blood draw)
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Concentration of serum lipidomic and biochemical biomarkers for AIH diagnosis assessed by integrated lipidomic and biochemical analysis
Periodo de tiempo: At enrollment (single time point - baseline blood draw)
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Identification of molecular biomarkers for early and accurate AIH diagnosis through integrated lipidomic and biochemical analysis
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At enrollment (single time point - baseline blood draw)
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Expression profile of EV-associated proteins and miRNAs involved in AIH pathogenesis assessed by proteomic and transcriptomic analysis
Periodo de tiempo: At enrollment (single time point - baseline blood draw)
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Identification of molecular pathways involved in AIH pathogenesis through EV characterization
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At enrollment (single time point - baseline blood draw)
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Colaboradores e Investigadores
Publicaciones y enlaces útiles
Publicaciones Generales
- Muratori L, Lohse AW, Lenzi M. Diagnosis and management of autoimmune hepatitis. BMJ. 2023 Feb 6;380:e070201. doi: 10.1136/bmj-2022-070201.
- Nishikawa H, Kim SK, Asai A. Autoimmune Hepatitis and Drug-Induced Liver Injury in Japan. J Clin Med. 2025 Jun 25;14(13):4514. doi: 10.3390/jcm14134514.
- Longhi MS, Zhang L, Mieli-Vergani G, Vergani D. Can we cure autoimmune hepatitis? Curr Opin Immunol. 2025 Oct;96:102609. doi: 10.1016/j.coi.2025.102609. Epub 2025 Jul 14.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- PR-23-26-NOTARNICOLA
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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