Patients With Cryptogenic Hypertransaminasemia (LIFT)
From the Gut to the Liver: Unraveling the Role of Bacterial Translocation in Cryptogenic Hypertransaminasemia
Persistent unexplained elevation of serum aminotransferases (ALT and AST) remains undiagnosed in a subset of patients despite a comprehensive diagnostic work-up. Increasing evidence suggests that alterations in the gut-liver axis, including intestinal dysbiosis, increased intestinal permeability, and bacterial translocation, may contribute to liver inflammation and hepatocellular injury. Bacterial components such as lipopolysaccharide (LPS) may reach the portal circulation and activate hepatic immune pathways through receptors including CD14 and Toll-like receptor 4 (TLR4).
This study aims to investigate the potential role of bacterial translocation in patients with unexplained persistent hypertransaminasemia undergoing liver biopsy. Standard histological evaluation will be integrated with immunohistochemical and molecular analyses of liver biopsy specimens to assess markers associated with bacterial translocation, including bacterial DNA, LPS, and soluble CD14 (sCD14). The study may help clarify the underlying mechanisms of otherwise unexplained hypertransaminasemia and identify potential biomarkers for future clinical use.
Studie Overzicht
Toestand
Conditie
Gedetailleerde beschrijving
The study will involve the collection of clinical, demographic, anthropometric, laboratory, medication, and imaging data from patients with persistent unexplained hypertransaminasemia. Relevant laboratory parameters will include liver function tests, metabolic parameters, complete blood count, glycated hemoglobin, and hepatitis B and C serological markers.
Additional biological samples will be collected during routine clinical procedures, including a 10 mL blood sample, a liver tissue specimen obtained during clinically indicated liver biopsy, and a stool sample. Liver tissue will undergo standard histological evaluation and additional immunohistochemical analyses. Blood and stool samples will be analyzed to investigate markers of bacterial translocation, intestinal microbiota composition, and inflammatory profiles, with the aim of better characterizing the gut-liver axis and its potential role in unexplained hypertransaminasemia.
All clinical data and biological samples will be collected only after obtaining written informed consent from participants, in accordance with the approval of the competent Ethics Committee. Biological samples and study-related data will be stored and processed at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.
Studietype
Inschrijving (Geschat)
Contacten en locaties
Studiecontact
- Naam: Francesca Romana Ponziani
- Telefoonnummer: 3471227242
- E-mail: francescaromana.ponziani@policlinicogemelli.it
Studie Contact Back-up
- Naam: Elisabetta Creta
- Telefoonnummer: 3480778584
- E-mail: elisabetta.creta@policlinicogemelli.it
Studie Locaties
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Roma, Italië, 00168
- Fondazione Policlinico Universitaro A. Gemelli IRCSS,UOC Medicina Interna e Gastroenterologia,Largo A. Gemelli,
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Contact:
- Francesca Romana Ponziani
- Telefoonnummer: 3471227242
- E-mail: francescaromana.ponziani@policlinicogemelli.it
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Contact:
- Elisabetta Creta
- Telefoonnummer: 3480778584
- E-mail: elisabetta.creta@policlinicogemelli.it
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Bemonsteringsmethode
Studie Bevolking
The study aims to enroll 30 patients with cryptogenic hypertransaminasemia and a control group of 10 participants with normal aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma.
Beschrijving
Inclusion Criteria:
- Age ≥ 18 years.
- Persistent cryptogenic hypertransaminasemia (elevated ALT and/or AST levels) documented for at least 6 months. For the control group only: normal aminotransferase levels.
- No identifiable etiology after a comprehensive clinical, laboratory, and instrumental evaluation.
- Ability to provide written informed consent.
Exclusion Criteria:
- Age < 18 years.
- Histologically documented metabolic dysfunction-associated steatotic liver disease (MASLD).
- Alcohol-related liver disease or active alcohol consumption.
- Active viral hepatitis.
- Hereditary hemochromatosis or other known genetic liver diseases.
- Adverse reactions to potentially hepatotoxic drugs.
- Celiac disease, thyroid disorders, rhabdomyolysis, or known muscle diseases.
- Ongoing acute infections.
- Systemic antibiotic or probiotic therapy within the 3 months preceding enrollment.
- Ongoing immunosuppressive therapy.
- Active malignancy.
- Pregnancy.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Observatiemodellen: COHORT
- Tijdsperspectieven: PROSPECTIVE
Cohorten en interventies
Groep / Cohort |
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Patients with cryptogenic hypertransaminasemia
Patients with cryptogenic hypertransaminasemia will undergo the collection of additional biological samples during routine clinical procedures. These will include an additional 10 mL blood sample, a liver tissue specimen for histological and immunohistochemical analysis, and a stool sample. The collection of these biological specimens will be performed as part of the routine clinical management and diagnostic work-up of patients undergoing evaluation for persistent hypertransaminasemia. |
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Healthy Controls
Control participants will be individuals with normal serum aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma. During routine clinical procedures, an additional 10 mL blood sample will be collected, together with a liver tissue specimen obtained during surgery for histological and immunohistochemical analysis. Participants will also be asked to provide a stool sample. The collection of these biological specimens will be performed in conjunction with routine clinical care and the surgical procedure. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Hepatic LPS Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of lipopolysaccharide (LPS) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
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Hepatic LBP Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of lipopolysaccharide-binding protein (LBP) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
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Hepatic CD14 Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of CD14 expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
|
Hepatic MD-2 Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of myeloid differentiation factor 2 (MD-2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
|
Hepatic TLR2 Expression
Tijdsspanne: 30-45 month
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Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
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Hepatic TLR4 Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of Toll-like receptor 4 (TLR4) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
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Hepatic TLR5 Expression
Tijdsspanne: 30-45 month
|
Immunohistochemical assessment of Toll-like receptor 5 (TLR5) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants. |
30-45 month
|
Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: Francesca Romana Ponziani, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
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Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 27818
Informatie over medicijnen en apparaten, studiedocumenten
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