The biliary and urinary excretion pattern of toxic and essential metals in patients with biliary and liver diseases and its association with fibrosis-4 index

Abstract

This study aimed to explore the urinary and biliary excretion of toxic and essential metals in 60 patients diagnosed with liver and biliary diseases and their potential association with hepatic fibrosis.  The levels of mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), selenium (Se), manganese (Mn), copper (Cu), and zinc (Zn) in patients’ urine and bile samples were determined using inductively coupled plasma-mass spectrometry. To assess hepatic fibrosis, we calculated the Fibrosis-4 (FIB-4) index, a non-invasive measure, using a formula incorporating age, aspartate aminotransferase, alanine aminotransferase, and platelet levels. The median values of biliary (urinary) Hg, Pb, Cd, As, Se, Mn, Cu, and Zn in µg.L⁻¹ were 2.7 (3.6), 1.6 (0.2), 0.126 (1.3), 0.319 (6.3), 14.1 (43.7), 43.4 (4.5), 244.3 (82.9), and 201.6 (692.5), respectively. Biliary levels of Pb, Mn, and Cu were significantly higher than those in urine (p for all <0.001), suggesting that these metals are primarily eliminated through biliary excretion. There was a clear imbalance in the biliary Cu and Zn levels; 33 (~57%) patients had a Cu/Zn ratio >1. FIB-4 index >1.3 was found in 28 patients at risk of liver fibrosis. Analysis of covariance revealed patients with FIB-4 index >1.3 had higher urinary levels of Pb (more than threefold) and Zn (approximately twofold) higher than those with lower FIB-4 scores. Conversely, patients with higher FIB-4 scores had significantly lower biliary levels of Mn (approximately fourfold) and Cu (more than twofold). These findings suggest that imbalances in certain metals may play a pivotal role in the pathophysiology of hepatic fibrosis, warranting further exploration.

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