Patients With Cryptogenic Hypertransaminasemia

NCT07834125 | Not Yet Recruiting

• 1 other identifier: 27818
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cryptogenic Hypertransaminasemia

Keywords

liver disease; liver cancer; Bacterial translocation; biomarker

Outcome Measures

Primary Outcomes (7)

• Hepatic LPS Expression

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

  30-45 month

• Hepatic LBP Expression

  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

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

  30-45 month

• Hepatic MD-2 Expression

  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

  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

  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

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

  30-45 month

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitaro A. Gemelli IRCSS,UOC Medicina Interna e Gastroenterologia,Largo A. Gemelli,

Roma, 00168, Italy

Location

MeSH Terms

Conditions

Liver Diseases; Liver Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Diseases; Digestive System Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• Francesca Romana Ponziani

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesca Romana Ponziani

CONTACT

3471227242; francescaromana.ponziani@policlinicogemelli.it

Elisabetta Creta

CONTACT

3480778584; elisabetta.creta@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2026
• First Posted: September 22, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2031
• Last Updated: September 22, 2026

Record last verified: 2026-09

Locations

IT (1)