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.

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.