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.

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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 antiimmunoglobulin A (IgA) class, but any binding to antiimmunoglobulin G and anti-immunoglobulin M classes was not observed. Although the incidence of ASTimmunoglobulin 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.

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 LDLchol 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.

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.