Lecithin: cholesterol acyltransferase activity in patients with chronic liver diseases and positive LP-X tests.

Lecithin: cholesterol acyltransferase activity has been measured in serum from patients with various liver disorders and positive LP-X tests and from healthy subjects. Statistical analysis indicated that lecithin: cholesterol acyltransferase activity provided no help in the discrimination between the persons of both groups although the mean activities differed significantly.     

Involvement of serum apolipoprotein AI and B100 and lecithin cholesterol acyl transferase in alcoholic cirrhotics

Lipoproteins are synthesized by the liver and secreted to plasma. Chronic alcoholic intoxication produces frequently cirrhosis and concomitantly alterations in liver metabolism. Thirty patients with alcoholic cirrhosis and 83 healthy controls were selected for this study. Apolipoprotein A1, B100, lecithin cholesterol acyltransferase, responsible for cholesterol esterification and seudocholinesterase enzyme activity not related to lipid metabolism, as a referent of proteins synthesized by the liver were analyzed. In 7 patients serum tiobarbituric acids, catalase, glutathione peroxidase were measured, as exponent of the presence of oxidative stress. Our results showed a significant decrease in lipoproteins, lecithin cholesterol acyltransferase and seudocholinesterase activities. An increase in serum tiobarbituric acids and a decrease in both antioxidant enzymes were found as well. In conclusion, alcohol cirrhotic liver decreases the production of liver proteins including those related to lipid metabolism, allowing the formation of steatosis and/or necrosis. Moreover oxidative stress participate possible as a major mechanism in liver damage.     

Clinical evaluation of serum biotin levels and biotinidase activities in patients with various liver diseases

In order to evaluate the clinical significance of serum biotin and biotinidase in liver disease, serum biotin levels and biotinidase activities were determined in 83 patients with various liver diseases and 10 healthy controls. Serum biotin levels and biotinidase activities were determined by a simplified lactobacillus plantarum bioassay and liquid chromatography with fluorimetric detection respectively. Serum biotin levels in decompensated liver cirrhosis, hepatoma and fulminant hepatitis were found to be significant low compared with healthy controls, while it was significant high in autoimmune hepatitis. There was no significant difference between serum biotin levels in the other liver diseases and healthy controls. In various liver diseases except for both acute hepatitis and alcoholic liver disease biotinidase activities were significantly reduced than in healthy controls. Serum biotinidase activities were correlated with serum albumin, prothrombin time, ChE and total cholesterol respectively, suggesting that biotinidase activities may reflect the degree of liver damage. These results seem that biotin deficiency may occur in some cases of severe liver diseases.     

A clinical evaluation of serum alpha-1-antichymotrypsin levels in liver disease and cancers

The serum levels of alpha-1-antichymotrypsin (ACT) were studied in 168 patients with various liver diseases and cancers in conjunction with other liver function tests, serum sialic acid, AFP and CEA. The ACT levels in acute viral hepatitis and chronic hepatitis were not significantly altered compared with the normal level (220 +/- 40 microgram/ml), although the level was slightly increased or decreased temporarily during the acute phase of the former. In liver cirrhosis, the mean level was significantly lower than the normal in spite of the absence of signs of hepatic decompensation (168 +/- 51 microgram/ml, p less than 0.001). In contrast to cirrhosis, the levels were increased to various extents in 65% of cases with hepatoma, in spite of the association of liver cirrhosis in the majority of them. Much higher levels were observed in all cases of metastatic liver cancers and cancers of the pancreas and the biliary tract. The elevations were observed even in cases without the increase of AFP or CEA. Both in cirrhosis and cancers, ACT levels were not correlated with any of serum bilirubin and serum enzyme activities, but were positively correlated with the levels of plasma fibrinogen and serum sialic acid. The measurement of serum ACT level can be taken advantage of for the diagnosis and monitoring of liver cirrhosis and liver cancers, particularly of hepatoma without AFP elevation.     

Human alpha 1-microglobulin in various hepatic disorders

Human alpha 1-microglobulin (alpha 1-m) levels were studied in the sera and urine of patients with various liver diseases. In patients with acute hepatitis and chronic hepatitis it was almost within the normal range. A significant decrease of serum alpha 1-m, however, was demonstrated in patients with compensated liver cirrhosis (p less than 0.05) as well as in those with decompensated liver cirrhosis (p less than 0.001). The most striking decrease was noted in patients with fulminant hepatitis (p less than 0.001). Its concentration in hepatoma was generally within the normal range, but there was 1 hepatoma case with the high concentration of alpha 1-m. Serum alpha 1-m levels correlated significantly with serum albumin, plasma fibrinogen and cholinesterase activity. As compared with the level in normal individuals, the patients with decompensated liver cirrhosis had significantly low urinary alpha 1-m (p less than 0.005), reflecting the findings for sera. These results indicated that the liver plays an important role in alpha 1-m synthesis, and its quantitation may be used for evaluating severe liver damage.     

Erythrocyte osmotic fragility in various liver diseases--application of coil planet centrifuge system

A change in erythrocyte osmotic fragility was observed on various liver diseases by means of the coil planet centrifuge (CPC) system, and the relationship between changes in it and in serum lipids was studied. According to the CPC classification of hemolytic patterns of L, M, T and R, the frequency of appearance of T and R increased in liver cirrhosis and primary hepatoma. Hemolytic start and end points both changed considerably in primary hepatoma, acute hepatitis and liver cirrhosis. Change of hemolytic end point which shifted to the hypotonic side is more prominent than that of hemolytic start point. The hemolytic end point showed an inverse correlation to serum alkaline phosphatase and LAP, and correlation to pseudocholinesterase and albumin. Among the relations of red cell fragility and lipids of the lipoprotein fractions, free cholesterol and the ratio of free cholesterol to phospholipid in high density lipoprotein were both in remarkable inverse correlation to the hemolytic end point. Free cholesterol in high density lipoprotein was concluded one of the most important determinants of erythrocyte osmotic fragility.     

Cholesteryl ester metabolism in fat- and cholesterol/fat-fed guinea pigs

Guinea pigs were fed a semisynthetic diet containing 10% (by weight) cottonseed oil with or without 1% cholesterol. In response to cholesterol/fat feeding there was a significant accumulation of cholesteryl ester (CE), particularly in the liver, but also in the kidney, spleen and suprarenal glands. The hepatic acyl-CoA:cholesterol acyltransferase (ACAT) increased 5-10 times when the animals were fed cholesterol fat during 11 weeks while the acid cholesterol esterase (CE-ase) was similar in the two dietary groups. Intestinal lymph showed the highest content of cholesterol (both free and esterified) in guinea pigs fed cholesterol/fat. A low activity of lecithin:cholesterol acyltransferase (LCAT) was present in the intestinal lymph, irrespective of dietary composition. Triglyceride-rich lipoproteins seem to inhibit LCAT activity in the intestinal lymph. Plasma cholesterol levels in animals fed cholesterol/fat increased markedly while LCAT remained unaffected by the diets. Activity of ACAT and CE-ase in kidney and spleen was low compared to liver tissue and the enzyme activities were not affected by the cholesterol/fat feeding.     

肝细胞癌变过程中维生素E水平改变及其作用机制研究

目的 探讨维生素Ｅ（Ｖｉｔ Ｅ）水平在肝细胞癌变过程中的改变与作用机制。方法 用２－ＦＡＡ制备大鼠肝癌动物模型,在肝细胞癌变过程中观察其肝组织学、肝总ＲＮＡ水平及血浃ＶｉｔＥ含量的动态改变,并对不同肝病患者血清中ＶｉｔＥ的浓度进行了分析。结果 在肝细胞癌变过程中,鼠血清中ＶｉｔＥ含量呈逐渐降低,而鼠肝总ＲＮＡ水平逐渐增加趋势;在急性肝炎、慢性肝炎、肝硬变和肝癌患者血清中ＶｉｔＥ含量均显著低于正常对     

Adenosine Deaminase Isoenzymes in Liver Disease

To clarify the clinical significance of increased serum adenosine deaminase (ADA) activity, and its mechanisms in various liver diseases, ADA isoenzyme activities (ADAI and ADA2) in serum and in peripheral blood mononuclear cells were studied. High serum ADA activities were found in patients with acute hepatitis, alcoholic hepatic fibrosis, chronic active hepatitis, liver cirrhosis, and hepatoma. The ADA2:ADA ratio was decreased in acute hepatitis, but was increased in chronic active hepatitis and liver cirrhosis. Clinically, ADA2 activity was correlated with serum γ-globulin levels. In chronic active hepatitis, total ADA activities in the peripheral blood mononuclear cells were similar to those in controls. Furthermore, ADA2 activities after phytohemagglutinin (PHA) stimulation were significantly lower than those without PHA stimulation, although total ADA activities were increased after PHA stimulation. These findings suggest that serum ADA isoenzyme activities may be a new marker for liver disease, and that the increased serum ADA2 in chronic active hepatitis is unlikely to be the result of an increase in ADA2 production by activated peripheral blood mononuclear cells.     

Changes of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis.

Serum angiotensin I converting enzyme, identical with kininase II, was measured fluorometrically in patients with acute viral hepatitis (n=18), liver cirrhosis without (n=44) and with (n=19) ascites. In all groups of patients the enzyme was significantly elevated as compared to 44 healthy controls (p less than 0.001). No correlation could be found between angiotensin I converting enzyme activity and liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, total protein, albumin, bilirubin) or other parameters (serum potassium, serum sodium). High serum converting enzyme activity in chronic liver diseases might originate primarily from an altered pulmonary circulation and indicates higher conversion rate of angiotensin I by passage through the lungs as well as increased bradykinin degradation. The reason for the enzyme liberation in acute viral hepatitis is as yet uncertain.     

Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase

Immunoaffinity chromatography has been used to study the determinants of sterol efflux and net transport from cultured fibroblasts to human plasma medium. Sterol efflux was highly (approximately 80%) dependent upon a minor lipoprotein fraction containing apolipoprotein A-I unassociated with other apolipoproteins. The remaining activity was associated with the lipoprotein-free fraction of plasma and could be replaced by apoprotein-free albumin. Efflux was independent of lecithin:cholesterol acyltransferase (EC 2.3.1.43) activity. Net transport (i.e., the excess of efflux over influx) was completely inhibited by inhibition of lecithin:cholesterol acyltransferase or its removal by affinity chromatography on immobilized antibodies to apolipoprotein A-I or D (components of the transfer complex in human plasma). In uninhibited plasma, efflux and net transport rates had similar kinetics, suggesting that these were linked functions and that net transport was initiated by a carrier-dependent efflux step that, in the absence of lecithin:cholesterol acyltransferase activity, was associated with an equivalent influx of free sterol to the cells and that, in the presence of lecithin:cholesterol acyltransferase, was associated with esterification and transfer protein activity. The cholesterol carrier lipoprotein function (approximately 5% of plasma apolipoprotein A-I) appears to be the first step of lecithin:cholesterol acyltransferase-linked sterol transport from cells.     

Urinary Pseudouridine as a Biochemical Marker in the Diagnosis and Monitoring of Primary Hepatocellular Carcinoma

The urinary level of pseudouridine, primarily a degradation product of transfer ribonucleic acid (tRNA), was determined in 38 patients with primary hepatocellular carcinoma, 18 with liver cirrhosis, 12 with chronic hepatitis, nine with acute hepatitis, and 28 healthy subjects. The mean urinary pseudouridine concentration was significantly higher in the patients with hepatoma [38.2 +/- 12.8 (SD) nmol/mumol creatinine] than in those with liver cirrhosis (20.3 +/- 6.8), chronic hepatitis (24.4 +/- 8.2), and acute hepatitis (21.7 +/- 8.2), and in healthy subjects (23.8 +/- 4.9). Urinary pseudouridine level was elevated above the mean value plus 2 SD for the healthy subjects (33.6 nmol/mumol creatinine) in 71% of our hepatoma cases. Serum alpha-fetoprotein levels correlated poorly with urinary pseudouridine levels, thus, the combination assay for urinary pseudouridine and serum alpha-fetoprotein could detect 79% of the patients with hepatoma. Moreover, urinary pseudouridine level was reduced after effective transcatheter arterial embolization therapy.     

Serum lysyl oxidase activity in patients with various liver diseases

Serum lysyl oxidase activity was examined in patients with various liver diseases. The activity of the enzyme was detected mainly in the serum fraction of the supernatant 80% saturated with (NH4)2SO4, and its molecular weight was estimated to be about 30,000 by Sephadex G-150 column filtration. Mean serum lysyl oxidase activity in 18 healthy controls was 129 +/- 50 (+/- SEM) cpm/ml and was significantly increased in patients with acute hepatitis, chronic active hepatitis, alcoholic liver disease and primary biliary cirrhosis, but not in those with chronic inactive hepatitis or liver cirrhosis. Serum lysyl oxidase activity was not correlated with the histological grade of hepatic fibrosis, but appeared to reflect active hepatic fibrogenesis in patients with liver diseases.     

Biotinidase Activity in Patients with Liver Disease

To investigate whether biotinidase deficiency may occur in liver disease, we determined biotinidase activity, biotin levels, and organic acids in patients with liver disease. Serum biotinidase activity in patients with liver disease (2.63 1.40 nmol/min/ml) was significantly lower than in the control group (5.43 1.06 nmol/min/ml). Serum biotinidase activity in decompensated liver cirrhosis (LC) and hepatoma was significantly lower than in acute viral hepatitis (AVH), chronic viral hepatitis (CVH), and compensated LC. The mean serum level of biotin in decompensated LC (1.8 0.6 μg/ml) and hepatoma (1.7 0.8μg/ml) was significantly lower than in the control group (2.5 1.0 μg/ml), and urinary excretion of biotin was increased in patients with liver disease, particularly in decompensated LC. Biotinidase activity correlated positively with serum biotin level and correlated negatively with urinary biotin level. Moreover, in four of five patients with severe liver disease the excretion of propionate, lactate, and 3-hydroxybutyrate decreased after biotin supplementation. The data for patients with severe liver disease so resembled those for late-onset multiple carboxylase deficiency that biotinidase deficiency is likely in patients with severe liver disease.     

腺苷脱氨酶活性与肝脏疾病的关系

目的：探讨腺苷脱氨酶在肝脏疾病中的诊断价值。方法：应用全自动生化分析仪检测肝病患者血清腺苷脱氨酶（ADA）及肝功能各项指标。结果：脂肪肝患者血清ADA无明显升高；慢性乙型肝炎、急性肝炎、肝硬化及肝硬化合并肝癌患者血清ADA活性明显增高，与正常组比较有统计学意义（P〈0．01）；肝硬化患者、肝硬化合并肝癌患者血清ADA活性较慢性乙型肝炎患者明显升高，两组比较有统计学意义P〈0．01）；急性肝炎患者经治疗血清ADA明显降低，与发病早期比较有统计学意义（P〈0．05）；肝病患者血清ADA与白球蛋白比值、前白蛋白呈负相关，与总胆红素呈正相关。结论：肝病患者血清ADA增高提示肝病慢性化、逐渐进展，反映肝脏损害程度加重，肝脏储备、合成功能逐渐降低。     

慢性肝病患者电解质异常的临床研究

研究慢性肝炎、肝硬化患者电解质异常情况。分别采用ELISA法、自动生化分析仪检测慢性肝炎轻度、慢性肝炎重度及肝硬化患者的肝功能、血生化。慢性重度肝炎与轻度比较血清Glu、Ca下降,肝硬化与重度比较BUN、Glu升高,Na、Ca、P、Mg均下降。随肝脏疾病的逐渐进展,病人低血Na、低血Ca的比例逐渐提高。BUN与血清白蛋白、胆碱脂酶呈负相关,Cr与胆碱脂酶呈负相关。Ca、Na、P均与血清白蛋白、胆碱脂酶呈正相关。随着慢性肝病进展,血电解质紊乱逐渐加重,血清Ca、Na、P水平可较好地反应肝脏的储备功能。     

Increased serum soluble interleukin 2 receptor levels in patients with viral liver diseases

Soluble interleukin 2 receptors (sIL 2R) in the sera of patients with viral liver diseases were quantified with a solid-phase enzyme immunoassay using two monoclonal antibodies against the receptors. The sIL 2R levels in patients with acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were significantly higher than those in control subjects. In acute hepatitis patients, the high levels of sIL 2R observed during the florid stage returned to normal during remission. Levels in patients with chronic active hepatitis were significantly higher than in those with chronic persistent and lobular hepatitis, and levels observed during the exacerbation phase of chronic hepatitis were higher than they were during remission. Thus, in chronic hepatitis, sIL 2R levels increased in proportion to the inflammatory activity, and correlated well with serum transaminase (glutamic oxaloacetic transaminase: SGOT, glutamic pyruvic transaminase: SGPT) activities, but not with blood urea nitrogen or creatinine concentrations. In patients with a high degree of focal and piecemeal necrosis, serum sIL 2R levels increased further during recombinant interleukin 2 therapy. In post-hepatitic liver cirrhosis and hepatocellular carcinoma, sIL 2R levels correlated with serum cholinesterase and creatinine concentrations, but not with transaminase activities. Measurement of serum sIL 2R levels in patients with liver disease but without renal injury, may help in the diagnosis of inflammation in hepatitis, a process in which interleukin 2 may participate.     

Angiotensin-converting enzyme in diseases of the liver

Serum angiotensin-converting enzyme activity was measured in various diseases of the liver. Activity increased in progressive order in patients with chronic persistent hepatitis, chronic aggressive hepatitis, and liver cirrhosis. Activity was increased also in patients with acute hepatitis. On the other hand, patients with fatty liver had normal angiotensin-converting enzyme activity and patients with extrahepatic obstructive jaundice showed subnormal activity. Although the mechanism for these enzymatic changes in diseases of the liver remains to be elucidated, serum angiotensin-converting enzyme determination may be useful in the diagnosis of diseases of the liver under certain conditions.     

Measurement of serum branched-chain amino acids to tyrosine ratio level is useful in a prediction of a change of serum albumin level in chronic liver disease.

Aim: In patients with hepatitis C virus (HCV)-associated chronic liver diseases, especially in those with liver cirrhosis, accurate evaluation of their protein nutrition status is very important to improve their quality of life. Whereas the serum albumin level is commonly used to evaluate patients' protein nutrition status, in the present study, the serum amino acid levels were measured, as they also provide valuable information. Methods: Serum albumin levels and branched-chain amino acids (BCAA) to tyrosine ratio (BTR) were determined in 447 patients with HCV-associated chronic liver diseases (313 with chronic hepatitis and 134 with liver cirrhosis). Results: Chronic hepatitis progressed to liver cirrhosis, serum albumin and serum BTR levels decreased significantlyas chronic hepatitis progressed to liver cirrhosis. Hypoalbuminemia was significantly more common in patients with liver cirrhosis than in those with chronic hepatitis; however, the incidence of an amino acid imbalance was significantly higher than that of hypoalbuminemia in patients with liver cirrhosis. The presence of an amino acid imbalance was associated with a reduction in the serum albumin level 1 year later. Conclusions: It is important to evaluate serum albumin levels and the BTR in patients with HCV-associated chronic liver diseases.     

Enzymic esterification of cholesterol in rat intestinal mucosa catalyzed by acyl-CoA: cholesterol acyltransferase

Previous work has shown CoA-dependent esterification of cholesterol in rat intestinal mucosa. Using (1-(14)C)oleoyl-CoA as the labeled substrate, we have proved that the esterification is catalyzed by acyl-CoA: cholesterol acyltransferase (ACAT) existing in the 'microsomal fraction' of the mucosal cell. The apparent K(m) for oleoyl-CoA is 25 microM, the optimal pH 7.4-7.9, and the optimal concentration of albumin 10-20 mg/ml. The reaction is rectilinear for only 2 min. Increasing the microsomal cholesterol concentration by incubation with plasma from patients with familial lecithin: cholesterol acyltransferase deficiency leads to increasing ACAT activity. The ACAT was inhibited by taurocholate and by the thiol-blocking agent 5,5'-dithiobis(2-nitrobenzoic acid). The specific activity of the enzyme is high-that is, approximately 1 nmol cholesteryl oleate formed x mg microsomal protein(-1) x min(-1).