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NCT Number: NCT07834125

Patients With 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.

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Key information

Conditions

Cryptogenic Hypertransaminasemia Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Hepatic LPS Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of lipopolysaccharide (LPS) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.

  2. Hepatic LBP Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of lipopolysaccharide-binding protein (LBP) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.

  3. Hepatic CD14 Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of CD14 expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.

  4. Hepatic MD-2 Expression

    Time frame: 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.

  5. Hepatic TLR2 Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.

  6. Hepatic TLR4 Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of Toll-like receptor 4 (TLR4) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.

  7. Hepatic TLR5 Expression

    Time frame: 30-45 month

    Immunohistochemical assessment of Toll-like receptor 5 (TLR5) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.

Study contacts

Contact information is provided by the study sponsor or research team.

Elisabetta Creta

CONTACT

[email protected]

3480778584

Francesca Romana Ponziani

CONTACT

[email protected]

3471227242

Sponsors and collaborators

Lead sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Other

Registry information

Official study title

From the Gut to the Liver: Unraveling the Role of Bacterial Translocation in Cryptogenic Hypertransaminasemia

Acronym: LIFT

Important dates

Study start
2026
Primary completion
2029
Study completion
2031
First posted
Sep 22, 2026
Registry last updated
Sep 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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