Hypermanganesemia in long-term intravenous nutrition and chronic liver disease

Background: Hypermanganesemia and cholestatic liver disease are both recogn ized complications of long-term IV nutrition. Manganese is primarily excret ed in bile, and recent studies have indicated that manganese toxicity may p lay a role in the pathogenesis of IV nutrition-associated cholestasis. Meth ods: Whole blood and plasma manganese concentrations were measured in patie nts receiving long-term home IV nutrition (HIN, n = 30). Whole blood mangan ese concentrations also were measured in patients with chronic liver diseas e (CLD, n = 10) and control subjects (n = 10). Results: Whole blood mangane se concentrations of all. CLD patients were within the reference interval ( 73 to 210 nmol/L) and were not different from those of the control group (1 51 +/- 44 nmol/L, CLD vs 155 +/- 35 nmol/L, control; not significant), desp ite the presence of cholestasis. In contrast, whole blood manganese concent ration was increased (>210 nmol/L) in 26 patients, and plasma manganese con centration increased (>23 nmol/L) in 23 of the patients receiving HIN. None of the patients exhibited neurologic signs of manganese toxicity. There wa s no correlation between whole blood manganese concentrations and markers o f cholestasis, IV manganese intake, or duration of HIN. However, plasma man ganese concentration correlated both with average weekly IV manganese intak e (r = .44, p = .02) and with gamma-glutamyl transferase (r = .43, p = .02) and alkaline phosphatase activities (I = .55, p = .003). Conclusions: Chol estatic liver disease does not appear to contribute to increased whole bloo d manganese concentrations in patients not receiving HIN. Plasma manganese concentrations in patients receiving HIN reflect recent manganese exposure and impaired excretion where cholestasis is present. The lack of relationsh ip between plasma and whole blood manganese concentrations suggests that fa ctors other than manganese intake and excretion affect intracellular concen trations.