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Patients With Cryptogenic Hypertransaminasemia (LIFT)

16. september 2026 opdateret af: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Detaljeret beskrivelse

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.

Undersøgelsestype

Observationel

Tilmelding (Anslået)

30

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

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.

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Observationsmodeller: COHORT
  • Tidsperspektiver: PROSPECTIVE

Kohorter og interventioner

Gruppe / kohorte
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.
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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Hepatic LPS Expression
Tidsramme: 30-45 month

Immunohistochemical assessment of lipopolysaccharide (LPS) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
30-45 month
Hepatic LBP Expression
Tidsramme: 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
Hepatic CD14 Expression
Tidsramme: 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
Tidsramme: 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
Tidsramme: 30-45 month

Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
30-45 month
Hepatic TLR4 Expression
Tidsramme: 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
Hepatic TLR5 Expression
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Efterforskere

  • Ledende efterforsker: Francesca Romana Ponziani, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. oktober 2026

Primær færdiggørelse (Anslået)

1. oktober 2029

Studieafslutning (Anslået)

1. oktober 2031

Datoer for studieregistrering

Først indsendt

16. september 2026

Først indsendt, der opfyldte QC-kriterier

16. september 2026

Først opslået (Faktiske)

22. september 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

16. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 27818

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