An observational study in Cryptogenic Hypertransaminasemia, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Not yet recruiting at 1 site in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Observational
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.
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.
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.
Exclusion Criteria:
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.
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.
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
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
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
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
Hepatic TLR2 Expression
Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Time frame: 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.
Time frame: 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.
Time frame: 30-45 month
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Fondazione Policlinico Universitario Agostino Gemelli IRCCS