Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease

Objective: We wanted to know if alterations in plasma cobalamin (B-12) concentration and B-12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B-12 distribution. Method: Total B-12, as well as B-12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis-a protozoan reagent served to measure only metabolically active (true) B-12. Total B-12 as distributed in hero TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease. Results: Severe liver disease initiates highly elevated B-12, levels in plasma and a lowered liver tissue total B-12 concentration. The percent of B-12 distributed to hole TC II is significantly depleted during liver disease. In contrast, hole TC I and III are elevated in plasma during liver disease and contain more B-12 than controls. Total B-12 and B-12 distributed to TC are lower in diseased liver tissue. Conclusion: Severe alcoholic liver disease involves leakage of total B-12 from liver tissue into the plasma. Hole TC I and III concentration increases in plasma; this preserves the high plasma B-12 from being excreted. However, plasma holo TC II B-12 distribution is decreased, indicating that there is a depression of exogenous B-12 entering the plasma and tissues. In severe liver disease, liver tissue B-12 binding and storage by TC is disrupted and causes B-12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B-12 deficits to cause metabolic dysfunction despite elevated plasma total B-12. Elevation of plasma B-12, accompanied by a lowering of hole TC II distribution, seemed to be a useful index of liver disease severity suggesting preventative treatment.