Hiroaki Ikezaki

Plasma glycated albumin level and atherosclerosis: Results from the Kyushu and Okinawa Population Study (KOPS)

BACKGROUND Glycated albumin (GA) is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. This study was done to test the hypothesis that GA can serve as a marker for atherosclerosis, similar to glycosylated hemoglobin A1c (HbA1c). METHODS HbA1c, plasma GA and serum high-sensitivity C-reactive protein (hs-CRP) levels were measured for 1575 residents (age range 26-78 years) of a suburban town in Japan. Carotid artery intima-media thickness (IMT) was measured by ultrasound for each participant. RESULTS GA levels had significantly positive correlation coefficients with HbA1c level, hs-CRP level, and max-IMT (all P<0.001). Receiver operating characteristic curve analysis indicated a GA level of ≥ 15.5% to be optimal for predicting diabetes. A GA level of 15.5% corresponded to an HbA1c level of 5.8%. The hs-CRP and max-IMT values of participants with GA ≥ 15.5% were significantly higher than the values of those with GA <15.5% (median hs-CRP: 2.4 vs. 2.3mg/L, P=0.048; mean max-IMT 0.852 vs. 0.759 mm, P=0.003, respectively). Among obese participants, the hs-CRP and max-IMT values of those with GA ≥ 15.5% (7.5mg/L and 1.014 mm) were significantly higher than the values of those with GA <15.5% (4.7 mg/dL and 0.823 mm) (P=0.024 and P=0.001, respectively). CONCLUSIONS Increased IMT and hs-CRP levels were associated with a high GA level, especially for obese participants, suggesting that GA would be as a useful biomarker for assessing the risk of atherosclerosis.

Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis B patients treated with nucleoside analog

Aim:  To evaluate the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of long‐term nucleoside analog (NA) treatment for patients with chronic hepatitis B.

Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial

BACKGROUND & AIMS Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. METHODS One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 μg/week and RBV 600-1,000 mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. RESULTS One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. CONCLUSIONS RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.

Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1

BACKGROUND & AIMS Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). METHODS This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. RESULTS No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55). CONCLUSIONS For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

Ribavirin concentration in the later stages of 48 week pegylated interferon-α2b plus ribavirin therapy for chronic hepatitis C is useful for predicting virological response

OBJECTIVES The current standard of care for chronic hepatitis C patients is a pegylated interferon-α plus ribavirin combination treatment. This study was carried out to determine the relationship between ribavirin concentration in the later stages of treatment and virological relapse. PATIENTS AND METHODS Serum ribavirin concentration of 183 chronic hepatitis C patients (genotype 1) treated with pegylated interferon-α2b plus ribavirin for 48 weeks was prospectively measured by HPLC at weeks 4, 12, 24, 36 and 48. Patients with undetectable serum hepatitis C virus (HCV) RNA 24 weeks after the end of treatment were designated as having sustained virological response (SVR). Patients with undetectable HCV RNA during the treatment but with virological relapse after the end of treatment were designated relapse. RESULTS The mean ribavirin concentration at each testing point of patients with SVR (1401, 1725, 1803, 1811 and 1901 ng/mL) was significantly higher than that of relapse patients (998, 704, 607, 643 and 654 ng/mL) at weeks 4, 12, 24, 36 and 48, respectively (all P < 0.001). Multivariate regression analysis for relapse extracted ribavirin concentration at week 36, but not cumulative ribavirin dosage. The cut-off value by receiver operating curve analysis for predicting a relapse was 1503 and 1562 ng/mL at weeks 36 and 48, respectively. CONCLUSIONS Ribavirin concentration in the later stages of treatment is an important marker of viral relapse.

Glycated albumin as a diagnostic tool for diabetes in a general Japanese population

OBJECTIVE Diabetes mellitus is a major cause of cardiovascular, kidney, neurologic, and eye diseases, and may be preventable in some cases by lifestyle modification. Screening tests for diabetes mellitus include fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Our objective was to evaluate the utility of plasma glycated albumin (GA) in the diagnosis of diabetes mellitus. DESIGN AND METHODS A cross-sectional, community-based population study of 908 non-diabetic Japanese residents was conducted. Of these subjects, 176 with FPG value between 5.5 and 6.9mmol/l, and an HbA1c level of <6.5% received an oral glucose tolerance test (OGTT). RESULTS The OGTT results were used for the diagnosis of diabetes mellitus using World Health Organization criteria. Receiver operating characteristic (ROC) analyses demonstrated that optimal threshold values for the diagnosis of diabetes in this population were 15.2% for GA and 5.9% for HbA1c, respectively. Using these cutoff levels, the sensitivity of GA at 62.1% for detecting diabetes was the same as that of HbA1c. However the specificity for GA for detecting diabetes was 61.9%, while for HbA1c it was higher at 66.7%. CONCLUSIONS Our results indicate that the measurement of glycated albumin may serve as a useful screening test for diabetes in a general Japanese population.

Serum cholesterol and triglyceride reference ranges of twenty lipoprotein subclasses for healthy Japanese men and women.

AIM This epidemiological study was done to generate normal ranges for the cholesterol and triglyceride levels in serum lipoprotein subclasses isolated from healthy adults based on gender and menopausal status. METHODS Cholesterol and triglyceride levels in 20 lipoprotein subclasses as separated by high performance liquid chromatography were measured in serum obtained from 825 fasting healthy subjects (267 men, 558 women). RESULTS For serum cholesterol, 13.7% was found in very low density lipoprotein (VLDL) subclasses, 55.6% in low density lipoprotein (LDL) subclasses, and 30.4% in high density lipoprotein (HDL) subclasses. For serum triglycerides, these values were 52.1%, 27.9%, and 17.4%, respectively. Levels of cholesterol in some VLDL subclasses were inversely correlated with the levels of some HDL subclasses, while for triglycerides, elevated levels in any one subclass were generally strongly associated with elevated levels in all other subclasses. Men had significantly higher large VLDL-cholesterol levels than women (P < 0.05), while women had significantly higher small VLDL-cholesterol levels than men (P < 0.001). Women had significantly higher large LDL- and large and medium HDL-cholesterol levels than men (P < 0.001). Men had significantly higher chylomicron (CM), large and medium VLDL-, and small LDL-triglyceride levels than women (P < 0.001). Women had significantly higher very large and large HDL-triglyceride levels than men (P < 0.01). Postmenopausal women had significantly higher CM, all VLDL, and large, medium and small LDL-cholesterol levels, and significantly higher all VLDL, LDL, and HDL-triglyceride levels than premenopausal women (P < 0.001). CONCLUSIONS Our data document important gender and menopausal status differences in cholesterol and triglyceride subclass levels, as well as significant correlations between values in the various serum lipoprotein subclasses.

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B

AIM To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B. METHODS Seventy-nine patients (age at the evaluation of PKTD: 56.9±10.7 years) with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited. PKTD was defined by the presence of at least two of the following five abnormalities: phosphate diabetes, nondiabetic glucosuria, metabolic acidosis, β2-microglobulinuria, or renal hypouricemia. The single-nucleotide polymorphisms (SNPs) in the SLC22A6 gene encoding human organic anion transporter 1 (hOAT1) and ABCC2 encoding multidrug resistance protein 2 (MRP2) were analyzed using the TaqMan Allelic Discrimination Demonstration Kit. RESULTS Nine (30.0%) of the 30 ADV-treated patients were diagnosed with PKTD, while no patients without ADV developed PKTD (P<0.001). Three patients with ADV were diagnosed with symptomatic osteomalacia. Among the patients who took ADV, those with PKTD were of higher age at initiation, had significantly longer treatment duration, and had a significantly lower body mass index than those without PKTD. The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration. In contrast, the SNPs were not correlated with PKTD. Logistic regression analysis extracted older age at initiation (OR=5.0, 95%CI: 1.1-23.4; P=0.040) and longer treatment duration (OR=3.2, 95%CI: 1.2-8.6; P=0.020) as significant factors associated with PKTD. CONCLUSION Our results suggest that the tubular function of the kidney of older patients undergoing long-term ADV treatment should be carefully evaluated.

Treatment for Eradication of Helicobacter pylori Infection among Chronic Hepatitis C Patients.

Background/Aims Helicobacter pylori infection causes gastritis, peptic ulcers and gastric malignancies, and its eradication has been advocated by many groups. We determined the H. pylori carrier status and eradication rates of patients with chronic hepatitis C virus (HCV) infection. Methods In total, 76 chronically HCV-infected patients were enrolled for comparison with 228 HCV-noninfected, age- and sex-matched controls. H. pylori infection was confirmed by H. pylori antibody and urea breath testing. Results The H. pylori infection rate was significantly higher for HCV-infected patients (67 of 76, 88.2%) than for HCV-noninfected controls (158 of 228, 69.3%). Endoscopic findings showed that the rates of gastric ulcers and gastritis were significantly higher for the 67 HCV-infected patients with H. pylori infection (34.3% and 77.6%) than for the 158 HCV-noninfected controls with H. pylori infection (15.2% and 57.6%). Treatment to eradicate H. pylori had a significantly higher success rate for HCV-infected patients (61 of 67, 91.0%) than for HCV-noninfected controls (115 of 158, 72.8%). Conclusions The markedly high H. pylori eradication rate observed in this study shows that eradication of H. pylori holds promise for the improvement of the long-term health condition of patients with chronic HCV infection.

The utility of urinary myo-inositol as a marker of glucose intolerance

OBJECTIVE The most common screening tests for glucose intolerance are fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Because it reflects the current status of hyperglycemia, urinary myo-inositol (UMI) may be useful. We evaluated UMI as a screening tool for glucose intolerance. DESIGN AND METHODS A cross-sectional, community-based population study of 1057 Japanese residents. 173 with an FPG level between 5.5 and 6.9 mmol/L and an HbA1c under 6.5% had an oral glucose tolerance test. We measured UMI level before (fasting UMI) and 2h after (2h-UMI) glucose ingestion. Δ-UMI was defined as the difference between fasting UMI and 2h-UMI. RESULTS Δ-UMI, 2h-UMI and HbA1c levels significantly increased as glucose intolerance worsened. Δ-UMI level was significantly positively correlated with 2h-UMI level (r=0.896, p<0.001). Using cutoff levels from receiver operating characteristic (ROC) analyses, the sensitivity of Δ-UMI (82.1%) and 2h-UMI (79.3%) were higher than that of HbA1c (48.3%). The area under the ROC curve values for Δ-UMI (0.903) and 2h-UMI (0.891) were higher than that for HbA1c (0.785). CONCLUSIONS 2h-UMI is useful as a non-invasive screening of glucose intolerance.