Patients With Cryptogenic Hypertransaminasemia

Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorFondazione Policlinico Universitario Agostino Gemelli IRCCS

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

Age < 18 years.

Histologically documented metabolic dysfunction-associated steatotic liver disease (MASLD).

Alcohol-related liver disease or active alcohol consumption.

Active viral hepatitis.

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

30 Participants
are grouped into 2 trial groups
Group A: Patients with cryptogenic hypertransaminasemia
Group B: Healthy Controls

Trial outcomes

Primary outcomes

1

Hepatic LPS Expression

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

Time frame
30-45 month
2

Hepatic LBP Expression

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

Time frame
30-45 month
3

Hepatic CD14 Expression

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

Time frame
30-45 month
4

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.

Time frame
30-45 month

Secondary outcomes

Other outcomes

Sponsors and contacts

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