Kazuharu Matsuura

Relationship between serum leptin and fatty liver in Japanese male adolescent university students

Relationship between serum leptin and fatty liver in Japanese male adolescent university students

Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases.

Background and aim: Complement receptor type 1 (CR1) is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC) from the circulation to the reticuloendothelial system, including the liver and spleen. In chronic viral hepatitis, increased levels of IC containing viral particles and an association with various extrahepatic manifestations have been reported. However, regulatory mechanisms for IC levels are not fully understood. Patients/subjects and methods: We analysed IC, E-CR1, and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent assay, radioimmunoassay, and polymerase chain reaction-restriction fragment length polymorphism, respectively. We also analysed the effect of CR1 gene polymorphism on IC binding to E-CR1 using molecular methods. Results: E-CR1 levels in patients with chronic hepatitis and chronic viral liver diseases as a whole correlated inversely with increased levels of IC. Moreover, significantly high levels of IC were observed in patients with chronic hepatitis C (CH-C) who were homozygous for the E-CR1 low density allele. We also found low levels of E-CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were observed, even after considering the polymorphism of the CR1 gene. Finally, we demonstrated CR1 gene polymorphism dependent binding of hepatitis virus containing IC. Conclusions: Our results emphasise the important role of E-CR1 in clearance of IC from the circulation and the acquired, rather than inherited, decrease in E-CR1 in chronic viral liver diseases, especially of type C.

Relationship between adrenomedullin and vasopressin-aquaporin system under general anesthesia.

Aim: The roles of adrenomedullin (AM) in body fluid balance under general anesthesia were investigated. Methods: Time course changes in plasma osmolality, AM, arginine vasopressin (AVP), and urinary aquaporin 2 (AQP2) in 17 patients undergoing abdominal surgery under general anesthesia were examined. Results: Increases in plasma AM levels were observed in parallel with increases in the levels of urinary AQP2/creatinine (Cr) before induction and 90 and 180 min after initiation of anesthesia. Significant correlations between plasma AM and urinary AQP2/Cr (r = 0.62, p < 0.0001) as well as urinary AVP/Cr and AQP2/Cr (r = 0.60, p < 0.0001) were uncovered. Multivariate stepwise analysis identified plasma AM as the critical independent factor affecting urinary AQP2/Cr level. Conclusion: A novel correlation of AM and AQP2 which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia.

Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m2) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p<0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but Gn therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH.

Changes in serum levels of hepatitis B virus markers after interferon treatment

SummaryThe effect of interferon (IFN) treatment on serum levels of pre-S antigens [pre-S(1) antigen, pre-S(2) antigen, polymerized human serum albumin receptor (pAR)] which are coded by the pre-S region of hepatitis B virus DNA (HBV-DNA), and HBV-markers was analyzed in 23 patients with chronic hepatitis B. One year after IFN treatment, 4 patients (Group C) became HBeAg negative. Six patients (Group B) transiently became HBeAg-negative, but reverted to HBeAg positive. Thirteen patients (Group A) remained HBeAg positive. All of the patients remained HBsAg-positive. Initiation of IFN treatment was rapidly followed by reduction or loss of DNA-P in the serum whether the patients became HBeAg negative or remained positive, and whether serum transaminase (S-GPT) levels became normal or not after IFN treatment. Group C patients, in whom pre-S antigens decreased rapidly during IFN treatment and disappeared before S-GPT levels normalized, became HBeAg negative one year after IFN treatment. Anti-pAR was detected in three out of these 4 patients. In contrast, Group A and Group B patients, in whom pre-S antigens decreased slowly during IFN treatment and did not disappear in spite of those patients being transiently negative for HBeAg and DNA-P, remained HBeAg positive with elevated S-GPT levels one year after IFN treatment. Anti-pAR was almost undetectable. These results suggest that testing for pre-S antigens is more useful for determining the prognosis of patients with chronic hepatitis B treated with IFN than testing for HBsAg, HBeAg and DNA-P.

Clinical significance of low or negative titer of antibody to hepatitis B core antigen during the course of chronic hepatitis B virus infection in adolescents.

SummaryAntibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay in 127 asymptomatic hepatitis B surface antigen (HBsAg) carriers (ASC; mean age 19) who had normal serum alanine aminotrasferase (ALT) levels and 16 patients with chronic hepatitis B (CH; 19). All 16 CH patients, who were positive for hepatitis B e antigen (HBeAg) and 5 ASC cases who were negative for both HBeAg and its antibody (anti-HBe), had high anti-HBc titers. Anti-HBc titers in 27 (56.3%) of the 48 HBeAg-positive ASC and 18 (24.3%) of the 74 anti-HBe-positive ASC were relatively low. Two of the ASC were HBeAgpositive/ anti-HBc-negative. In a follow-up study of the 19 HBeAg-positive ASC with low or negative anti-HBc titers, 5 had abnormal serum ALT levels and increased anti-HBc titers. In contrast, in the other 14 of these subjects, serum ALT levels remained normal and the low anti-HBc titers remained unchanged and/or decreased. The serological profile of HBsAg-positive/low or negative anti-HBc titer and increased anti-HBc titer with abnormal serum ALT levels are not necessarily exceptional in HBeAg-positive adolescent ASC. It is suggested that anti-HBc is associated with the liver damage that occurs before adolescence in chronic hepatitis B virus infection.

Changes of pre-Sl and pre-S2 antigens in sera of patients with hepatitis B virus infection

SummaryPolypeptides encoded by the pre-Sl and pre-S2 genes of hepatitis B virus (HBV) (pre-Sl antigen and pre-S2 antigen) were detected by enzyme-linked immunosorbent assay (ELISA) in 137 serum samples of patients with HBV infection. The HBV-DNA level closely correlated with the titer of pre-S antigens. However, HBV-DNA levels more closely correlated with the titer of the pre-Sl antigen [HBV-asymptomatic carrier (ASC): n=40, r=0.800, P<0.01; chronic hepatitis B (CH): n=60, r=0.730, P<0.01] than with the titer of the pre-S2 antigen [ASC: r=0.675, P<0.01; CH: r=0.575,P<0.01]. Thirty patients with CH, in whom hepatitis e antigen (HBeAg) was cleared after acute exacerbation (AE) [alanine aminotransferase (ALT) level> 200 IU/L] and the ALT level normalized, were followed for 12 months and classified into two groups: Group 1, those in whom HBeAg reappeared with an elevated ALT level within 12 months, and Group 2, those in whom HBeAg was persistently cleared from the serum and a normal ALT level continued. Of the 30 patients, 24 (80%) were classifed into Group 1 and 6 (20%) were classified into Group 2. Changes in serum levels of HBV markers a month before and after AE were observed. The HBV-DNA level and DNA-P activity became negative after AE in both groups. The titer of pre-Sl antigen also decreased after AE, and no significant differences were observed between Group 1 and Group 2. In contrast, the titer of pre-82 antigen and pAR activity decreased more significantly in Group 2 than in Group 1. These results suggest that the detection of the pre-S2 antigen and pAR activity in sera seems to be more useful as a prognostic test for patients with HBV infection than the detection of pre-Sl antigen, HBV-DNA, DNA-P or HBeAg.