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Patients With Cryptogenic Hypertransaminasemia (LIFT)

16. september 2026 oppdatert av: 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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Detaljert 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.

Studietype

Observasjonsmessig

Registrering (Antatt)

30

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Observasjonsmodeller: COHORT
  • Tidsperspektiver: PROSPECTIVE

Kohorter og intervensjoner

Gruppe / Kohort
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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. oktober 2026

Primær fullføring (Antatt)

1. oktober 2029

Studiet fullført (Antatt)

1. oktober 2031

Datoer for studieregistrering

Først innsendt

16. september 2026

Først innsendt som oppfylte QC-kriteriene

16. september 2026

Først lagt ut (Faktiske)

22. september 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

22. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

16. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 27818

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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