Lecithin: cholesterol acyltransferase in liver disease

Lecithin: cholesterol acyltransferase (LCAT) activity in patients with liver disease has been found to be either normal or lower than normal, but no information on LCAT mass in these patients is available. In this study, LCAT mass concentration together with LCAT activity and cholesterol esterification rate were measured in the plasma of 19 patients with cholestatic liver disease and 21 patients with non-cholestatic liver disease. The LCAT mass in plasma correlated positively with serum albumin (r = 0.69, p less than 0.001) and pre-albumin (r = 0.77, p less than 0.001) and negatively with serum bilirubin (r = -0.42, p less than 0.01) and bile salts (r = -0.43, p less than 0.01), thus reflecting the severity of liver disease and liver protein synthesizing capacity. In plasma, LCAT mass concentration also correlated well with LCAT activity (r = 0.88, p less than 0.001) and cholesterol esterification rate (r = 0.73, p less than 0.001), thereby indicating that the decrease of LCAT activity and cholesterol esterification rate in liver disease is primarily a function of decreased LCAT mass.     

Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: association with ballooning degeneration

Our aim was to examine the relation of serum osteocalcin (OCN) levels with the clinical, biochemical, and histological characteristics of patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). We carried out a case-control study including 99 patients with biopsy-proven NAFLD and 75 age- and sex-matched controls. Concentrations of OCN were measured in aprotinin-treated serum samples using a solid-phase enzyme amplified sensitivity immunoassay. Serum OCN levels were significantly lower in patients with NAFLD than in healthy controls. In patients with NAFLD, serum OCN levels were inversely associated with ALT (r = -0.36, p < 0.001), AST (r =-0.39, p < 0.001), HOMA-IR (r = -0.30, p < 0.01) and the degree of hepatocyte ballooning (r =-0.20, p < 0.05). Serum OCN was the only independent predictor of the degree of hepatocyte ballooning in NAFLD patients (β = -0.24; t = -2.146, p < 0.05). Compared with controls, NAFLD patients have a decrease in serum OCN concentrations, which is significantly associated with serum transaminases and the extent of hepatocyte ballooning.     

Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease

The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two radioimmunoassays using different purification procedures and antibody batches did not differ significantly and correlated significantly (r=0.91; p less than 0.001). The median serum concentration of non-protein bound testosterone was 0.265 nmol/l (range 0.068-0.495 nmol/l) when determined by equilibrium dialysis and 0.232 nmol/l (range 0.042-0.610 nmol/l) when calculated according to the law of mass action. This difference is insignificant. The concentrations of non-protein bound testosterone determined by the two methods correlated significantly (r=0.83; p less than 0.001). In the calculation of non-protein bound testosterone, the actual serum albumin concentration can be replaced by a fixed albumin concentration (r=0.99; p less than 0.001). Further, in these patients the serum concentration of non-protein bound testosterone can be expressed by the testosterone/SHBG ratio (r=0.97; p less than 0.001).     

Selenium concentrations in the blood and urine of a healthy Polish sub-population

Selenium (Se) levels in whole blood, red blood cells, and plasma taken from 199 healthy subjects were investigated and found to be 101.1 micrograms/1 (whole blood), 133.1 micrograms/1 (packed red blood cells), and 78.0 micrograms/1 (plasma). In 62 samples of urine, the selenium level, expressed as micrograms/g creatinine, was 11.4. The mean whole blood selenium concentration was significantly higher in men than women: 104.5 +/- 23.2 vs. 96.9 +/- 21.2 micrograms/1. No differences were found in red blood cells, plasma and urine between male and female subjects. A strong linear correlation was observed between red blood cell and whole blood selenium levels (r = 0.879; p less than 0.001) as well as between selenium levels in whole blood and plasma (r = 0.806; p less than 0.001). A weaker but still significant linear correlation was found between urine and whole blood as well as between urine and plasma selenium concentrations. The relatively low levels of the element in the blood and urine are probably due to its deficiency in the diet.     

Estimation of the production rates of serum aminoterminal propeptide of type III procollagen and laminin in human fibrotic liver

The concentrations of laminin, a high molecular weight non-collagenous glycoprotein of basement membranes, and of the N-terminal propeptide of type III procollagen were determined in the serum of the liver outflow vascular region (hepatic vein) and of a peripheral vein (cubital vein) in patients with chronic liver diseases (fibrosis, cirrhosis, unspecified histology; n = 173), in order to determine their secretion rates from the injured livers. The mean levels of laminin (1.84 kU/l) and of procollagen peptide (28.0 micrograms/l) in hepatic vein were significantly higher (about 9.5% at p less than 0.02, and 37% at p less than 0.001, respectively) than those in the periphery (1.68 kU/l and 20.4 micrograms/l, respectively). In chronic liver diseases, however, laminin and procollagen peptide concentrations in the hepatic vein were lower than or equal to those in the cubital vein in 18% and 27% of patients, respectively. The highest regional differences of the concentrations were noted in cirrhotic subjects. The serum levels of laminin (rs 0.93) and of procollagen peptide (rs 0.73) in hepatic and in cubital vein are highly positively correlated (p less than 0.001), but the levels of procollagen peptide in hepatic vein are only weakly but still significantly statistically related with those of laminin (rs 0.446, p less than 0.001). Similarly, the hepatic-cubital venous concentration differences of both proteins are weakly (rs 0.312) but significantly (p less than 0.001) correlated. On the basis of several assumptions we estimated secretion rates from the livers of 120 U.min-1 for laminin, and 5.7 micrograms.min-1 for procollagen peptide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between increased concentrations of free thyroxine and unsaturated free fatty acids in non-thyroidal illnesses: role of albumin

We measured the concentrations of non-esterified free fatty acids and free and total thyroid hormones in serum from patients with various non-thyroidal illnesses (NTI) and chronic renal failure (CRF). The total concentration of free fatty acids was measured enzymatically and the eight most abundant fractions were determined by gas-liquid chromatography. The concentration of total free fatty acids was significantly increased in the NTI group as compared with controls (p less than 0.01); the concentrations of oleic, linoleic and linolenic acid were increased more than those of the other fractions. In NTI the serum-free thyroxine (FT4) concentration was increased (p less than 0.01) and the free triiodothyronine (FT3) concentration was decreased (p less than 0.001); these concentrations were measured by equilibrium dialysis. There was a significant correlation between the levels of total free fatty acids and FT4 in the NTI (n = 43) group (r = 0.45, p less than 0.01), and also between the levels of linoleic acid and FT4 (r = 0.35, p less than 0.05). The serum albumin concentration was decreased in the NTI group, and when free fatty acid to albumin molar ratios were calculated stronger correlations with FT4 were observed (total free fatty acids: r = 0.55; p less than 0.001; oleic acid: r = 0.30, p less than 0.05; linoleic acid: r = 0.46, p less than 0.01; linolenic acid: r = 0.35, p less than 0.05). There was no correlation between FT4 and unsaturated FFA concentrations in CRF patients, who had normal mean FT4 and total FFA levels. These results support the hypothesis that unsaturated fatty acids are involved in the increase of serum FT4 in NTI, especially when albumin levels are low.     

Localization of T and B cells and alpha fetoprotein in hepatic biopsies from patients with liver disease.

Peripheral blood and hepatic tissue T- and B-lymphocyte distributions, serum alpha fetoprotein (AFP) concentrations, and hepatic AFP were studied in 46 patients undergoing diagnostic percutaneous liver biopsy. The patients included 26 with alcoholic liver disease, 13 with nonalcoholic hepatitis or cirrhosis, and 7 with either normal histology or minor nonspecific changes. Serum AFP was determined by radioimmunoassay and hepatic tissue AFP by indirect immunofluorescence. Peripheral blood T lymphocytes were identified by the sheep red-cell rosette technique; and B lymphocytes by fluoresceinated anti-immunoglobulin antisera and IgG aggregates. Tissue identification of T lymphocytes was accomplished using an extensively absorbed rabbit antihuman thymocyte antiserum and indirect immunofluorescence; tissue B lymphocytes were identified using pepsin F (ab')2 fragments of rabbit IgG antibodies to human immunoglobulins. T lymphocytes predominanted in hepatic lymphoid infiltrates from patients with alcoholic liver disease (91+/-4%), whereas in patients with chronic active or chronic persistant hepatitis, viral hepatitis, or cryoptogenic cirrhosis proportions of T and B lymphocytic infiltrates were similar (50+/-15%). Hepatic tissue AFP was detected in 9 of 18 patients with alcoholic hepatitis; serum AFP concentration was increased in only 1 of these 9 patients. Tissue AFP was not observed in the remaining biopsy material nor were serum AFP concentrations increased. Peripheral blood T-cell numbers were significantly decreased in patients with alcoholic liver disease (P less than 0.01) and in nonalcoholic hepatitis or cirrhosis (P less than 0.025). A close relationship between peripheral blood T-lymphocytopenia and hepatic T-cell infiltrates was observed in patients with alcoholic liver disease; this relationship was less apparent in patients with nonalcoholic hepatitis or cirrhosis.     

Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease

To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting the degree of liver fibrosis, we measured radioimmunologically the concentrations of 7S collagen, laminin fragment P1, and the aminoterminal propeptide of type III procollagen (P-III-P) in serum from 48 patients with chronic viral liver disease: chronic persistent hepatitis (9), chronic active hepatitis (13), chronic active hepatitis with lobular disorganization (17), and liver cirrhosis (9). Concentrations of 7S collagen, laminin P1, and P-III-P in serum were increased in respectively 92%, 69%, and 77% of the patients with both chronic active hepatitis with lobular disorganization and liver cirrhosis. Concentrations of 7S collagen and laminin P1 in serum correlated well (r = 0.65, P less than 0.001, and r = 0.55, P less than 0.001, respectively) with the histological grade of liver fibrosis, whereas P-III-P correlated only weakly (r = 0.33, P less than 0.05). Evidently, measurement of serum 7S collagen is a reliable noninvasive test for detection of fibrosis in chronic viral liver disease.     

Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis

The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6.0 pmol l-1 (range 0-20) in 112 normal subjects. In fifty-three patients with decreased kidney function plasma VIP was significantly increased (median 15.0 pmol l-1, range 0.5-70, P less than 0.0001) and positively correlated to serum creatinine concentration (r = 0.51, P less than 0.001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7.0 pmol l-1 range 0-86, P less than 0.01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P less than 0.05, n = 6) and in patients with cirrhosis (median 60%, P less than 0.02, n = 8), but not in uraemic patients (median 0%, NS n = 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (-42%, P less than 0.05, n = 6 and -45%, P less than 0.01, n = 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (-4%, NS, n = 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition.     

Decreasing effects of iron toxicosis on selenium and glutathione peroxidase activity

Heart failure due to chronic iron overload is a leading cause of cardiovascular mortality in the second and third decades of life worldwide, but its mechanism is not known. Deficiencies of selenium have been shown to result in damage to the myocardium and to the development of various cardiomyopathies. In the current investigation, the dose-dependent effects of chronic iron toxicosis on heart tissue concentrations of selenium and the protective antioxidant enzyme glutathione peroxidase (GPx) were investigated in a murine model of iron-overload cardiomyopathy (n = 20). Significant dose-dependent decreases in heart tissue selenium concentrations (r = -0.95, p < 0.001) and selenium-dependent GPx activity (r = -0.93, p < 0.001) were observed in chronically iron-loaded mice in comparison with placebo controls. These results suggest that dietary supplementation with selenium may be beneficial in the clinical management of disorders of iron metabolism.     

Iron, copper, zinc and selenium in human liver tissue measured by X-ray fluorescence spectrometry

The content of iron, copper, zinc and selenium was measured by energy-dispersive X-ray fluorescence (XRF) spectrometry in normal liver tissue obtained at autopsy from 16 females and 12 males 46-87 years old. The precision of the XRF analysis, expressed by the coefficient of variation was: iron, 1.8%; copper, 3.2%; zinc, 1.0%; and selenium, 26.7%. In large liver samples, mean amount-of-substance contents of elements in dry liver tissue were: iron, 16.95 mmol/kg (range 7.90-27.31 mmol/kg); copper, 0.33 mmol/kg (0.08-0.76 mmol/kg); zinc, 5.12 mmol/kg (2.92-9.47 mmol/kg); selenium 0.02 mmol/kg (less than 0.004-0.04 mmol/kg). Furthermore the amounts of iron, copper and zinc were measured in wet-ashed Menghini needle biopsy specimens taken from the centre of 20 large liver samples. There was good agreement between results obtained in biopsy specimens and large samples concerning iron (r = 0.96, P less than 0.001) and zinc (r = 0.97, P less than 0.001), but not concerning copper (r = 0.66, P less than 0.01). XRF analysis appears to be a convenient method for element analysis in liver tissue and for measurement of iron and zinc in needle biopsy specimens.     

Insulin-like growth factors (IGF) in liver disease: differential changes of IGF-I and IGF-II

IGFs are growth hormone-dependent, serum growth factors which are secreted primarily by liver, although other tissues contribute. We have measured IGF levels in serum of patients with primary biliary cirrhosis (n = 28), primary sclerosing cholangitis (n = 10), and alcohol-induced liver disease (n = 16), and compared them to a group of healthy controls (n = 25). Serum IGF-I as measured by radioimmunoassay was significantly decreased in all patient groups to 30% of control. After acid gel chromatography, IGF-II, measured by radioreceptor assay, was slightly decreased (p less than 0.05) in primary sclerosing cholangitis patients, but not in the other liver disease patients, when compared to the controls. The regression of IGF-II vs IGF-I for primary biliary cirrhosis patients was significant, with r = 0.62, p less than 0.01 (n = 27). The mean ratio of IGF-II/IGF-I was significantly different for histologic stage 2 vs stage 3 vs stage 4 primary biliary cirrhosis patients, but stage 2 was not different from control. We suggest low IGF-I values may reflect compromised hepatocyte function, and secretion of IGF-I and IGF-II may be from different cell populations, or controlled by different mechanisms.     

Decreased serum lipoprotein levels as a guide for clinical severity in patients with idiopathic dilated cardiomyopathy

Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not fully clarified. It has been known that there is a direct relationship between the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and deteriorating functional classes of heart failure and mortality. The present study compared the levels of circulating TNF-alpha, IL-6, lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total cholesterol (TC) was significantly lower in stable IDC patients than controls (p < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but not statistically significant. The IDC patients had significantly higher concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and Apo AI levels were significantly different between stable and unstable IDC patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = -0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p < 0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum levels of cytokines in patients with IDC are associated with decreased lipoprotein concentrations, which may indicate impaired prognosis.     

血清丙氨酸氨基肽酶测定在脂肪肝诊断中的应用

目的研究血清丙氨酸氨基肽酶(AAP)的测定对脂肪肝的临床诊断价值。方法用自动分析仪连续监测法测定189例健康对照者、150例脂肪肝患者和80例肝胆疾病患者血清AAP含量。结果脂肪肝病例组血清AAP活力明显高于健康对照组(P<0·001);AAP与常见的肝功能酶学指标ALT、γ-GT、ALP、CHE相比,其在脂肪肝诊断中的灵敏度最高(68%);AAP与γ-GT和ALT呈明显的正相关性,相关系数分别为0·8598和0·7088;肝胆病例组血清AAP活力明显高于健康对照组(P<0·05)。结论在脂肪肝诊断中,AAP较其它肝功能酶学指标具有更高的灵敏度,但无鉴别诊断意义。     

Studies of glucose intolerance in cirrhosis of the liver

Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied 21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT) were performed, and timed blood samples were obtained for the assay of glucose immunoreactive insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All results were compared to those of similar studies performed on healthy controls. During OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis (2 hr plasma glucose 198.8 +/- 14.3 mg/dl in cirrhosis and 116.4 +/- 4.2 in controls; p less than 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic patients than in controls (p less than 0.001; less than 0.001; less than 0.025). In response to IVAST, the patients with cirrhosis showed a greater first-phase insulin secretion and controls had a slightly better second-phase insulin release. Plasma IRG rose from a basal value of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls. After intravenous insulin administration, there was only a 40% decline in plasma glucose concentration from basal values in the patients with cirrhosis whereas the controls showed a 60% decline, demonstrating that the patients with cirrhosis had significant insulin resistance. Moreover, the half-life of insulin was prolonged in the patients with cirrhosis (t 1/2 = 15.5 min in cirrhosis and 10.3 in controls; p less than 0.001); and the ratio of C-P to insulin during OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and 4% in lean controls. There was a significant negative correlation between the fasting plasma insulin values and the specific binding of insulin. In conclusion, patients with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia, hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia is primarily due to increased pancreatic secretion.     

The role of IgA1 rheumatoid factor in the formation of IgA-containing immune complexes in Henoch-Sch?nlein purpura

The present study was performed to investigate the role of IgA rheumatoid factor (RF) in the formation of IgA-containing immune complexes and to determine the IgA subclass composition of IgA RF in patients with Henoch-Sch?nlein purpura (HSP). Immune complexes were isolated from the sera of 22 children with HSP and 13 controls by means of polyethylene glycol (PEG) precipitation. The percentage of IgG, IgA, and IgM precipitated by PEG was significantly greater in HSP patients than controls (p less than 0.01). There was a strong correlation (r = 0.723, p less than 0.001) between the amount of IgG and IgA in the PEG precipitates from HSP patients, but not controls. HSP patients had significantly higher levels of IgA RF in their serum (p less than 0.05) and in their PEG precipitates (p less than 0.05) compared to controls. There was a strong correlation between IgA RF concentrations in the serum and PEG precipitates in HSP patients (r = 0.910, p less than 0.001). PEG precipitation eliminated IgA RF activity from the serum of 7 of 8 HSP patients tested, and substantially reduced the titer in the remaining patient. IgA RF was recovered in the PEG precipitates from all patients. Testing of HSP patients showed that IgA1 was the predominant IgA subclass of the serum IgA RF (p less than 0.02) and PEG precipitate IgA RF (p less than 0.01). These results indicate that IgA RF is a constituent of IgA-containing immune complexes in HSP, and that IgA RF is composed primarily of IgA1.     

Heavy metal and trace element concentrations in patients with idiopathic dilated cardiomyopathy

Blood, serum and urine concentrations (24 hour samples) of cadmium, lead, magnesium, calcium, zinc, copper and iron were determined by means of atomic absorption spectrophotometry in 54 patients with dilated cardiomyopathy (CMP). These data were compared with the values in 17 healthy controls. CMP patients showed higher blood cadmium concentrations (+173%, p less than 0.001), higher serum calcium concentrations (+4%, p less than 0.01) and lower serum magnesium levels (-11%, p less than 0.01). In urine samples CMP patients had higher cadmium levels and lower concentrations of calcium (-43%, p less than 0.05) and magnesium (-36%, p less than 0.05). Correlations with clinical data revealed no definite reason for the abnormal laboratory findings in CMP patients. In individual cases, however, the high cadmium concentrations could be of aetiological importance.     

Apolipoproteins A-I, A-II and E in cholestatic liver disease

Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary biliary cirrhosis and one patient with sclerosing cholangitis). Plasma concentrations were measured by electroimmunoassay in the fasting state, postprandially after ingestion of either 100 g fat as whipping cream or a light mixed meal with or without addition of wheat fibre. Concentrations of apolipoproteins A-I and A-II were low in patients with cholestatic liver disease and A-I levels correlated inversely with the severity of liver disease as measured by bilirubin levels (r = -0.66). No changes in plasma apolipoprotein A-I, A-II or E concentrations occurred postprandially. There was an inverse correlation between plasma concentrations of apolipoproteins A-I and E (p less than 0.05, r = -0.68). A close relation existed between the ratio of apolipoprotein E to apolipoprotein A-I and plasma bile salt concentration (r = 0.80, p less than 0.01) and serum bilirubin (r = 0.76, p less than 0.01). This implies that in cholestatic liver disease apolipoprotein E and A-I levels reflect the degree of cholestasis.     

Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease

Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P less than 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P less than 0.05) but not in the other study groups.     

The retention of cobalamin by the liver in the cobalamin-deficient rat

The effect of cobalamin deficiency on whole body cobalamin content and its turnover was examined in the rat. Quantitative and qualitative changes in hepatic cobalamin were also followed and the effect of deficiency on the turnover of this cobalamin was determined in the isolated perfused liver. As cobalamin deficiency developed after total gastrectomy, whole body cobalamin content declined at a constant rate, indicating no attempt to conserve total body cobalamin stores even when depleted (5% of normal). In contrast, the cobalamin concentration of liver declined more slowly, indicating conservation of hepatic cobalamin. Furthermore, the methylcobalamin (MeCbl) content of liver was maintained or even increased. Measurement of the rate of release of cobalamin by the isolated perfused liver at varying times after gastrectomy showed that as depletion of whole body and hepatic cobalamin stores proceeded, the rates of release of hepatic cobalamin into plasma and bile decreased. Regression analysis showed that the fractional rates of release of hepatic cobalamin into plasma (r = 0.9, P less than 0.001, n = 15) and bile (r = 0.65, P less than 0.01, n = 15) were significantly correlated with hepatic cobalamin content. It is concluded that conservation of hepatic cobalamin in deficiency is achieved, at least in part, by a specific decrease in the rate of release of hepatic cobalamin.