Classification of hypocholesterolemia lipid patterns using Chol/Trig Combination System.

Patterns of hypocholesterolemic lipid fractions in 295 patients with liver diseases, malignant tumors, arteriosclerotic and renal diseases with cholesterol (Chol) levels of <30 mg/dl were classified using a simultaneous analytical method for the Chol and triglyceride (TG) fractions (Chol/Trig Combo System). Hypocholesterolemia was classified as follows: IV, Type IV on WHO hyperlipidemia phenotype classification; intermediate density lipoprotein (IDL), cases with appearance of IDL, including appearance of Lp(a); high + low density lipoproteins (HDL+LDL), lipids mostly consisting of HDL and LDL fractions; HDL abnormality, cases with slow alphaHDL or fast HDL; abnormal LDL, both Chol and TG fractions mostly consisting of LDL fraction; normal type, ratios of HDL, very low density lipoproteins (VLD) and LDL fractions were almost normal; and low HDL, HDL-C was <30 mg/dl. Many patients with liver diseases had HDL+LDL (45%), and abnormal LDL was noted in 13% of the cases. In malignant tumors, the frequencies of low HDL, normal type, and HDL+LDL cases were similar (22-30%). In arteriosclerosis, normal type accounted for 46% of the cases, and the frequency of normal type was higher (60%) in renal diseases. Mortality rate (within 1 year after measurement) was then compared among lipid patterns. In liver diseases, mortality rate increased in the following order: abnormal LDL (55%); low HDL (31%); HDL abnormality (25%); and HDL+LDL (21%). No deaths were seen among patients with normal type. In malignant tumors, mortality rate was very high (88%) in patients with HDL+LDL, but low in patients with normal type (22%) and low HDL (9%). Mortality rate was low in patients with arteriosclerosis and renal diseases in the short-term follow-up period (1 year). In the comparisons of distribution, mean, and appearance rate of charge modification frequency (CMF) among lipid patterns, parameters were high in all patterns other than HDL+LDL. Classification of hypocholesterolemia lipid patterns and evaluation of CMF may therefore be clinically useful.

High-molecular intestinal alkaline phosphatase by agarose gel electrophoresis.

The presence of high-molecular intestinal ALP (HIALP) overlapping with bone ALP in the alpha(2)beta region has been demonstrated. In this study we evaluated a method of separating HIALP after its conversion into ALP(5) by the action of protease. Serum samples from patients were mixed with protease at a ratio of 5:1 and left at room temperature for more than 30 min. The protease-treated and nontreated samples were both subjected to agarose gel electrophoresis. Patients who showed a decrease in ALP(3) in the alpha2beta region and an increase in ALP(5) in the beta region were regarded as HIALP-positive. HIALP was observed in 26.7-33.1% of patients with liver diseases, collagen diseases, and diabetes mellitus. Renal disease was ABO blood group-dependent and showed high positive rates for blood groups B and O. The HIALP-positive rate was low (7.1-15.5%) in patients with cardiovascular diseases, malignant tumors, and other disorders. ALP(5) was also observed in 98.4% of HIALP-positive patients with liver diseases. In patients with collagen diseases or diabetes mellitus, the positive rate of ALP(5) was 40.4-66.7%. In conclusion, this method, in which HIALP is converted into ALP(5) by protease pretreatment and is separated from bone ALP, allows HIALP to be identified while other fractions remain unaffected.

High-molecular intestinal alkaline phosphatase in chronic liver diseases.

The presence of high-molecular intestinal alkaline phosphatase (HIALP) different from bone ALP detected in the alpha(2)beta region was recently clarified. In this study we used a novel method in which HIALP was detected after conversion to ALP(5) by protease to investigate the clinical significance of the appearance of HIALP in patients with chronic liver disease. The subjects were 241 patients with chronic liver disease. When a decrease in ALP(3) in the alpha(2)beta region and an increase in ALP(5) in the beta region were noted, the patient was judged HIALP-positive. In the patients with chronic liver disease, the total ALP activity (T-ALP) increased with progression of the pathology in the order of chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). HIALP appeared in 22.4% and 49.3% of patients with CH and LC, respectively, but the positivity rate decreased to 30.4% in HCC. As autoimmune liver diseases, primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were investigated. T-ALP was lower in PBC+AIH than in LC and HCC, but the HIALP-positive rate was high (44.4%). The HIALP-positive rate was dependent on ABO blood groups, and was high in blood groups B and O. In conclusion, the HIALP-positive rate was particularly high in patients with chronic liver disease, and was related to the pathological progression, which suggests that the method is clinically useful.

Clinical significance of abnormal lipoprotein patterns in liver diseases.

We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.

Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease.

AIM: To determine the complex of AST and immunoglobulin and to investigate its clinical significance in patients with liver disease. METHODS: The complex of AST and immunoglobulin was determined by encounter immunoelectrophoresis and its clinical significance was investigated in 128 patients with liver disease. RESULTS: AST was bound to immunoglobulin of anti-immunoglobulin A (IgA) class, but any binding to anti-immunoglobulin G and anti-immunoglobulin M classes was not observed. Although the incidence of AST-immunoglobulin complex was 41.8% in chronic hepatitis (CH), the incidences in liver cirrhosis and hepatocellular carcinoma were 62.2 and 90.0%, respectively. In alcoholic liver disease with high level of serum IgA, the incidence of the complex was 66.7%, which was higher than that in CH. The ratio of binding to lambda-chain of IgA was higher than that to kappa-chain of IgA. The serum level of IgA and the ratio of AST/alanine aminotransferase (ALT) were significantly higher in patients with AST-IgA complex than in those without complex. CONCLUSION: These results suggest that AST-IgA complex in patients with progressive liver diseases and alcoholic liver injury can lead to elevation of the ratio of AST/ALT.

Effects of atorvastatin on serum lipids, lipoproteins, and hemostasis.

Serum levels of lipids and lipoproteins were examined in individuals with hyperlipidemia treated with atorvastatin or colestimide and in healthy volunteers. Modified low-density lipoprotein (LDL) was measured by its faster electrophoretic mobility and expressed as charge modification frequency (CMF). Serum levels of total cholesterol (t-chol), triglyceride (TG), very low-density lipoprotein (VLDL)-chol, low-density lipoprotein (LDL)-chol, and CMF were significantly higher in hyperlipidemia, but there was no significant difference in serum high-density lipoprotein (HDL)-chol levels between hyperlipidemic and healthy subjects. Treatment with atorvastatin resulted in significant decreases of serum t-chol, TG, and LDL-chol levels but not serum HDL-chol and VLDL-chol. Treatment with colestimide significantly reduced serum t-chol, HDL-chol, and LDL-chol levels but not those of TG and VLDL-chol. CMF was significantly reduced by treatment with atorvastatin but not by colestimide. Atorvastatin significantly reduced plasma levels of thrombomodulin, thrombin antithrombin complex (TAT) and tissue type plasminogen activator-plasminogen activator inhibitor-I complex. Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT. Based on its actions of lowering modified LDL and improving hemostatic abnormalities, we postulate that atorvastatin might inhibit the onset of ischemic diseases.