Serum cytokeratin 18 M30 antigen level and its correlation with nutritional parameters in middle-aged Japanese males with nonalcoholic fatty liver disease (NAFLD).

Cytokeratin (CK) 18 M30 antigen has been proposed as a diagnostic marker of nonalcoholic fatty liver disease (NAFLD). We studied serum CK18 M30 antigen level and examined the correlations among CK18 and biological data, dietary intake, and plasma fatty acid composition in middle-aged Japanese males with (NAFLD; n=42) and without NAFLD (control; n=35). NAFLD was diagnosed if subjects showed fatty liver on abdominal ultrasonography and their alcohol consumption was <20 g/d. They were also confirmed to have negative serological results for tests of autoimmune liver disease and hepatitis B and C. In the NAFLD group, body mass index, waist circumference, serum M30 antigen, alanine transaminase (ALT), cholinesterase, triacylglycerol, LDL-cholesterol, and HbA1c were significantly higher than in the control group. In the fatty acid analysis of plasma phospholipids, significantly higher dihomo-γ-linolenic acid (DGLA), total saturated fatty acids (SFA), and palmitic/linoleic acid ratio as well as lower arachidonic acid/DGLA ratio were observed in the NAFLD group compared with the control group. In the NAFLD group, M30 antigen was correlated positively with serum ALT, plasma DGLA, dietary SFA, and serum TNF-α as determined by partial correlation analysis controlled for BMI. On the basis of multivariate regression analysis using a stepwise method, M30 antigen was significantly associated with ALT and plasma DGLA. Regarding the determinants of NAFLD as revealed by logistic regression analysis, a high odds ratio was observed for plasma DGLA. In conclusion, members of the NAFLD group showed higher levels of serum CK18 M30 antigen and M30 antigen was strongly associated with serum ALT and plasma DGLA. Abnormal fatty acid metabolism may be a factor that causes aggravation of NAFLD.

Effects of eicosapentaenoic acid supplementation in the treatment of chronic hepatitis C patients.

Eicosapentaenoic acid (EPA) has been shown to exert anti-inflammatory actions. To evaluate the effects of EPA on chronic hepatitis C, we administered EPA ethyl ester capsules to patients receiving the combination therapy of interferon alpha-2b and ribavirin. EPA (1,800 mg/d) was supplemented in combination with vitamin E (300 mg/d) and C (600 mg/d) to 5 chronic hepatitis C patients (EPA group). Five patients were administered vitamin E and C but not EPA (control group). Blood samples were obtained before and after 4, 8, 12 and 24 wk of therapy and analyzed for fatty acid compositions of erythrocyte and plasma and serum 8-hydroxy-2'-deoxyguanosine. EPA in erythrocyte membrane rose to 3 fold the basal level in the EPA group, while it decreased significantly in the control group after 24 wk of therapy. Lymphocyte counts in the EPA group increased to 120.8 +/- 25.4% after 4 wk of therapy and maintained the basal level throughout therapy, whereas the counts decreased significantly in controls. The serum alanine aminotransferase level was improved significantly in the EPA group. Changes in lymphocyte counts following 24 wk of therapy correlated with the EPA level in erythrocyte. The serum 8-hydroxy-2'-deoxyguanosine level at 24 wk in the EPA group was significantly lower than that in controls. These observations may suggest the beneficial effect of EPA supplementation in the treatment of chronic hepatitis C patients.

Vitamin E supplementation increases polyunsaturated fatty acids of RBC membrane in HCV-infected patients.

OBJECTIVE: We investigated the effects of vitamin E supplementation on the fatty acid composition of red blood cell membrane phospholipids and on the clinical observations in patients with hepatitis C virus. METHOD: Eight patients and control subjects were administered 500 mg/d of d-alpha-tocopherol for 12 wk. The alpha-tocopherol and fatty acid composition of phospholipids in red blood cells were analyzed before, at 4, 8, and 12 wk, and after 4 wk of washout of vitamin E administration. RESULTS: The alpha-tocopherol concentration in red blood cells increased 2.37-fold of the basal level during vitamin E supplementation. Serum alanine aminotransferase levels increased in five of eight patients with vitamin E supplementation. The arachidonic acid level, docosahexaenoic acid level, and ratio of polyunsaturated to saturated fatty acid in red blood cell membrane phospholipids, which were significantly lower in the patients than in the control subjects, were elevated at 8 and 12 wk after vitamin E supplementation. The improvement in fatty acid composition was observed particularly in the patients who responded to the vitamin E therapy. CONCLUSIONS: Vitamin E therapy for the prevention of disease progression in patients with hepatitis C virus may be effective.

Arachidonic acid in mononuclear cells and its clinical significance in HCV cirrhotic patients.

OBJECTIVES: An abnormal fatty acid pattern in patients with advanced liver cirrhosis (LC) has been reported in plasma phospholipids and some other tissues. To elucidate the significance of arachidonic acid deficiency on the clinical pathophysiology of LC and hepatocellular carcinoma (HCC), we analyzed the fatty acid compositions of mononuclear cell phospholipids, plasma alpha-tocopherol, and thiobarbituric acid-reactive substances and serum tumor necrosis factor-alpha (TNF-alpha) in cirrhotic patients infected with the hepatitis C virus with and without HCC. METHODS: Twelve cirrhotic patients without HCC (LC patients) and 11 with HCC (HCC patients) were enrolled. Fatty acids were analyzed with gas chromatography. alpha-Tocopherol and TNF-alpha were analyzed by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Statistical analysis was performed by using the unpaired t test with Welch's correction and Spearman's rank-correlation analysis. RESULTS: Significantly low levels of linoleic, dihomo-gamma-linolenic, arachidonic, and eicosapentaenoic acids from mononuclear cell phospholipids were observed in LC and HCC patients compared with control subjects. Plasma alpha-tocopherol was lower and thiobarbituric acid-reactive substances were higher in HCC patients than in controls. Arachidonic acid molar percentage in mononuclear cell phospholipids correlated significantly with lymphocyte count (r = 0.460, P < 0.05) in the cirrhotic patients and with lymphocyte (r = 0.680, P < 0.01) and platelet (r = 0.763, P < 0.01) counts in all subjects. CONCLUSIONS: These results suggested that arachidonic acid in mononuclear cells may have an important role in the pathophysiology of hepatitis C virus associated with cirrhosis and that nutritional management preventing arachidonic acid deficiency may have some beneficial effects on the progression of LC.

Habitual food intake and polyunsaturated fatty acid deficiency in liver cirrhosis.

OBJECTIVE: We compared the habitual food intake and plasma fatty acid composition in cirrhotic patients living in two different regions in Japan, Okayama and Toyama, and evaluated the effects of dietary polyunsaturated fatty acid and alpha-tocopherol intake on serum alanine aminotransferase (ALT) activity. METHOD: A quantitative food-frequency questionnaire method was used. RESULTS: The significantly higher intake of fish in the patients living in Toyama resulted in higher plasma levels of docosahexaenoic acid and lower levels of arachidonic acid. Serum ALT activity correlated negatively with plasma arachidonic acid (r = -0.456, P < 0.05) and alpha-tocopherol (r = -0.505, P < 0.05) levels. Dietary intakes of vitamin E and polyunsaturated fatty acids (mg/g) correlated negatively with serum ALT (r = -0.377, P < 0.05). Dietary intake of linoleic acid and the ratio of polyunsaturated to saturated fatty acid in dietary fat correlated significantly with serum ALT (r = 0.604, P < 0.01, and r = 0.622, P < 0.01, respectively). The amount of vegetable intake correlated with intake of vitamin E and polyunsaturated fatty acid (r = 0.527, P < 0.02). CONCLUSIONS: These findings suggest that habitual food intake affects the plasma fatty acid profile and that elevated serum ALT may be related to arachidonic acid deficiency and vulnerability to lipid peroxidation in cirrhotic patients with hepatitis B and C viruses.