Folate Deficiency in Chronic Liver Disease.

By Fru rn mci A. Kur’sitm t m JoHN Li Er AUM S INCE THE INITIAL case reports in 1949,1,2 the occurrence of megaloblastic anemia as a complication of alcoholic cirrhosis has been reported with increasing frequency in recent years.314 Jarrold and Vilter reviewed the marrows of 30 patients with cirrhosis and found 3 to be megaloblastic.1 Krasnow et al. found the incidence of megaloblastic anemia in cirrhotics to be 7 per cent in a group of 96 patients who underwent bone marrow examination.5 Folic acid deficiency appears to be the underlying cause of the megaloblastic anemia associated with cirrhosis. Where serum assays have been performed, serum folate levels have been subnormal,#{176}13 and serum vitamin B12 levels have been normal or elevated.15-17 Hematologic responses to physiologic doses of 50 izg. of folic acid have been demonstrated in several of these patients;4’7’9 such responses are considered to be specific for folio acid deficiency.8’9’18 In other patients a seemingly “spontaneous” hematologic improvement, without added hematinic therapy, has been attributed to quantities of free folic acid present in the hospital diet approximating 50 to 100 ILg. a day.4’8’9 All of the reported cases of megaloblastic anemia in cirrhosis have been in chronic alcoholics, usually with a history of a poor dietary intake and evidence of malnutrition and multiple vitamin deficiencies. No cases of megaloblastic anemia in nonalcoholic individuals with postnecrotic cirrhosis have been reported to date. There have been several reports of megaloblastic anemia associated with hemochromatosis, but all of these patients have been chronic alcoholics.19’20 Thus, Jarrold’ and Herbert8 have speculated that dietary deficiency of folic acid is the principal factor leading to megaloblastic anemia in cirrhotics. On the other hand, Cherrick and his associates have proposed that decreased hepatic avidity for folic acid, and a possible deficiency in enzymes necessary in the metabolism of folic acid may play a significant role.21 In a recent study reported from Boston, Herbert, Zalusky, and Davidson found subnormal serum folate levels in 80 per cent of a group of 70 poorly nourished alcoholic cirrhotics.7”2 Morphologic abnormalities characteristic of folate deficiency were observed in the peripheral blood smears and in bone marrow aspirates when obtained from 31 patients who had serum folate levels below 3.0 m, g./ml. as well as from the majority of the 25 patients who had folate concentrations of 3.0 to 4.9 m,zg./ml. The nature of the patient material studied by this group precluded any conclusions regarding correlations be-