COBALAMIN (VITAMIN-B-12) AND HOLOTRANSCOBALAMIN CHANGES IN PLASMA ANDLIVER-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 l iver disease. Our purpose was to test the hypothesis that liver diseas e may disrupt B-12 distribution.Method: Total B-12, as well as B-12 bo und to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas m alhamensis-a protozoan reagent served to measure only metabolically ac tive (true) B-12. Total B-12 as distributed in hero TC in plasma and l iver tissue of healthy subjects (controls) were compared to patients w ith severe alcoholic liver disease. Results: Severe liver disease init iates highly elevated B-12, levels in plasma and a lowered liver tissu e 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 m ore B-12 than controls. Total B-12 and B-12 distributed to TC are lowe r in diseased liver tissue. Conclusion: Severe alcoholic liver disease involves leakage of total B-12 from liver tissue into the plasma. Hol e TC I and III concentration increases in plasma; this preserves the h igh plasma B-12 from being excreted. However, plasma holo TC II B-12 d istribution is decreased, indicating that there is a depression of exo genous 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 dis ease could produce enough severe tissue B-12 deficits to cause metabol ic 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 t reatment.