ELSEVIER PII S0741-8329(96)00103-6 Alcohnl, Vol. 14. No. 1, pp. 394-4, 1997 Copyright'> 1997Elsevier ScienceInc. Printed in the USA,All rightsreserved 0741-8329/97$17.00÷ .00 Zinc, Copper, Manganese, and Iron in Chronic Alcoholic Liver Disease F. RODRIGUEZ-MORENO,* E. GONZ~LEZ-REIMERS,* F. SANTOLARIA-FERNANDEZ,* L. GALINDO-MARTIN,? O. HERNANDEZ-TORRES,~" N. BATISTA-LOPEZ* AND M. MOLINA-PEREZ* *Dpto. de Medicina Intern& Hospital Universitario de Canarias, La Laguna, Tener~fe, Canary Islands, Spain )Dpto. de Quirnica Analitica, Universidad de La Laguna, Tener(fe, Canary Islands, Spain Received 24 January 1996: Accepted 1 May 1996 RODRIGUEZ-MORENO, F., E. GONZ~LEZ-REIMERS. F. SANTOLARIA-FERNANDEZ, L. GALINDO-MARTIN, O. HERNANDEZ-TORRES, N. BAT1STA-LOPEZ AND M. MOLINA-PEREZ. Zinc, copper, manganese, and iron in chronic alcoholic liver disease. ALCOHOL 14(1) 39-44, 1997.--Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron, zinc, copper, and manganese. This alteration may play a role on ongoing liver fibro- genesis. Based on these facts we have determined liver, serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics and noncirrhotics with normal renal function, comparing them with those of controls. We have observed low liver zinc and high liver copper--this last in relation with histomorphometrically determined total amount of liver fibrosis--and manganese contents in cirrhotics, together with increased excretion of zinc and iron and decreased excretion of manganese. Zinc, iron, and copper excretion kept a relation with data of severity of cirrhosis, including mortality in the case of urinary cop- per, independently of the use of diuretics. Thus, liver copper and urinary iron, zinc, and copper excretion seem to be related with data of severity of chronic alcoholic liver disease. Low urinary manganese excretion may play a role on liver manganese overload. Copyright~ 1997Elsevier Science Inc. Iron Zinc Copper Manganese Alcoholic liver disease Fibrogenesis PROGRESSIVE liver fibrosis is observed in chronic alcoholic liver disease. Liver fibrogenesis is a complex process in which collagen fibres are formed together with a protein matrix composed of proteoglycans, glucosaminoglycans, and other proteins as laminin (34). Some trace elements, especially iron and zinc, play important roles as cofactors of several enzymes involved in collagen synthesis (1,34,39) and other potentially hepatotoxic metabolic events (40). So, hepatic iron overload, observed in 30% of alcoholics with chronic liver disease (7), alters lysosomal membranes and favours lipid peroxidation, both factors leading to hepatocyte necrosis (3.27). It also acti- vates transcription of genes responsible for collagen synthesis (32), enhances hepatic prolylhydroxilase activity (6), and in- creases hepatic collagen fibrils content (5). Low liver zinc content has been observed in alcoholics (25,26,41). It may be responsible for progressive liver fibrosis. Indeed, Anttinen et al. (1) have shown that zinc supplementa- tion hampers carbon tetrachloride induced liver fibrosis in rats. High liver manganese content has been reported in alco- holic liver disease, probably because of impaired biliary ex- cretion (25). Manganese acts as cofactor of enzymes involved in collagen synthesis (34), and, by this way, manganese over- load may affect hepatic fibrogenesis. Excessive liver copper concentrations have been reported in cholestatic syndromes (38) and in alcoholic cirrhosis (37). Both liver copper excess--by promoting necrosis (38) and en- hancing lysyl-oxidase activity (34)--and depletion-altering su- peroxide dismutase activity (33) may affect liver fibrogenesis. Thus, alteration in copper, zinc. iron, and manganese me- tabolism may be related to histological and/or clinical events in chronic alcoholic liver disease. Based on these facts, in the present study we analyze the relationship between liver, se- rum, and urinary content of these elements and clinical and biological parameters in chronic alcoholics. METHOD Patients Forty-nine alcoholic patients entered the study, 6 of them women. All of them were heavy consumers of alcoholic bev- Requests for reprints should be addressed to Dr, Gonztilez-Reimers, Dpto. de Medicina lnterna, Hospital Universitario de Canarias, La La- guna, Tenerife, Canary Islands, Spain. 39