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1.
Aliment Pharmacol Ther ; 52(5): 866-876, 2020 09.
Article in English | MEDLINE | ID: mdl-32697871

ABSTRACT

BACKGROUND: A strong association between chronic hepatitis C (CHC) and hepatic steatosis has been reported. However, the influence of steatohepatitis on hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) elimination remains unclear. AIM: To evaluate the development of HCC after HCV cure using a new steatohepatitis-related biomarker. METHODS: This cohort study analysed the prospective database of 290 CHC patients without a history of HCC who achieved HCV elimination by direct-acting antivirals. We calculated the FibroScan-aspartate aminotransferase (FAST) score 12 weeks after the end of treatment (pw12). The risk of HCC was analysed using the multivariable Cox proportional hazard model. RESULTS: HCV genotype (GT)1 was most prevalent at 72.4%, followed by GT2 (26.6%). Median follow-up period was 4.2 years (IQR 3.1-4.5). The cumulative HCC incidence for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35 (log-rank test: P < 0.001). The annual HCC incidence rate for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35, in patients with liver stiffness measurement (LSM) ≥10 kPa (adjusted hazard ratio [HR] 4.41, 95% confidence interval [CI] 1.30-15.0, P = 0.018). After adjusting for variables, including age, albumin, alpha-fetoprotein, the patatin-like phospholipase domain-containing the 3 (PNPLA3) rs738409 genotype, and pw12 fibrosis markers with FIB-4, non-alcoholic fatty liver disease fibrosis score, and LSM, FAST score ≥ 0.35 was associated with the development of HCC (adjusted HR 4.42, 95% CI 1.02-19.9, P = 0.043). CONCLUSIONS: Steatohepatitis-related biomarkers with the FAST score are helpful for predicting the development of HCC after HCV elimination.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/diagnosis , Fatty Liver/diagnosis , Hepacivirus/physiology , Hepatitis C, Chronic/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Antiviral Agents/therapeutic use , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Transformation, Viral , Cohort Studies , Disease Progression , Fatty Liver/blood , Fatty Liver/genetics , Female , Genotype , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Polymorphism, Single Nucleotide , Prognosis , Remission Induction , Retrospective Studies , alpha-Fetoproteins/genetics
2.
Intern Med ; 58(18): 2737-2741, 2019 Sep 15.
Article in English | MEDLINE | ID: mdl-31178505

ABSTRACT

A 37-year-old woman presented to our hospital with mild abdominal pain experienced for 2 months and hepatic nodules in segments 3 and 8. Peripheral blood eosinophilia was observed, and toxocariasis was serologically diagnosed. Seventeen days after the first imaging evaluation, a new lesion was found in segment 9 of the right lung, which was contiguous through the diaphragm to the hepatic nodule in segment 8. After treatment with albendazole, the liver and lung nodules disappeared. We suspect that larvae had directly invaded the lung from the liver, through the diaphragm.


Subject(s)
Larva Migrans, Visceral/diagnosis , Liver Diseases, Parasitic/diagnostic imaging , Lung Diseases, Parasitic/diagnostic imaging , Abdominal Pain , Adult , Albendazole/therapeutic use , Anthelmintics/therapeutic use , Antiviral Agents/therapeutic use , Diaphragm , Eosinophilia , Female , Hepatitis C/complications , Hepatitis C/drug therapy , Humans , Larva Migrans, Visceral/complications , Larva Migrans, Visceral/drug therapy , Liver Diseases, Parasitic/complications , Liver Diseases, Parasitic/drug therapy , Lung Diseases, Parasitic/complications , Magnetic Resonance Imaging , Toxocariasis/complications , Toxocariasis/diagnosis , Toxocariasis/drug therapy
3.
Intern Med ; 57(1): 121-126, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29021433

ABSTRACT

A 39-year-old Japanese man presented to our hospital complaining of left chest pain and rash on the hands and feet. Plain thoracic computed tomography (CT) revealed multiple nodular shadows in the left lower lobe of the lung. A diagnosis of secondary syphilis was made based on the appearance of the rash and positive serologic tests for syphilis. The patient was started on amoxicillin but was switched to minocycline due to amoxicillin-induced rash on both forearms. Thoracic CT after five months of treatment revealed that the multiple lung nodular shadows had contracted, and secondary syphilis with pulmonary involvement was diagnosed.


Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Lung/physiopathology , Minocycline/therapeutic use , Syphilis/drug therapy , Syphilis/physiopathology , Treponema pallidum/isolation & purification , Adult , Asian People , Humans , Lung/microbiology , Male , Serologic Tests , Syphilis/diagnosis , Tomography, X-Ray Computed , Treatment Outcome
4.
Liver Int ; 38(1): 76-83, 2018 01.
Article in English | MEDLINE | ID: mdl-28618152

ABSTRACT

BACKGROUND & AIMS: Despite a known risk of hepatitis B virus (HBV) reactivation during direct-acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV)-HBV coinfection, it remains unclear whether patients with past HBV infection are at risk for reactivation. This study evaluated the risk of HBV reactivation during treatment with sofosbuvir (SOF)-based regimens, focusing on patients with resolved HBV infection. METHODS: This study analyzes the data of 183 consecutive patients treated with SOF-based regimens. From these patients, 63 with resolved HBV infection (negative for hepatitis B surface antigen [HBsAg] and undetectable HBV DNA but positive for hepatitis B core antibody) were eligible for this study. HBV reactivation was defined as a quantifiable HBV DNA level >20 IU/mL. RESULTS: Among the patients antibody to HBsAg (anti-HBs) positive (10-500 mIU/mL) (n = 30), the titre of anti-HBs was significantly decreased with time, as shown by the results of repeated-measures analysis of variance (P = .0029). Overall, four patients (6.3%) with resolved HBV infection came to have detectable HBV DNA during treatment, including one who had HBV reactivation at week 4 (HBV DNA 80 IU/mL). However, none developed hepatic failure. Among four patients who had detectable HBV DNA during treatment, all were negative or had very low-titre (<20 mIU/mL) anti-HBs at baseline. CONCLUSIONS: The titre of anti-HBs was significantly decreased from the early stage of DAA treatment. Chronic hepatitis C patients with resolved HBV infection and negative or very low-titre anti-HBs at baseline are at risk for having detectable HBV DNA transiently during treatment.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis B virus/drug effects , Hepatitis B/virology , Hepatitis C, Chronic/drug therapy , Virus Activation/drug effects , Aged , Antiviral Agents/adverse effects , Benzimidazoles/therapeutic use , DNA, Viral/blood , DNA, Viral/genetics , Female , Fluorenes/therapeutic use , Hepacivirus/pathogenicity , Hepatitis B/blood , Hepatitis B/diagnosis , Hepatitis B Antibodies/blood , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Risk Assessment , Risk Factors , Sofosbuvir/therapeutic use , Time Factors , Treatment Outcome
5.
Int Urol Nephrol ; 48(6): 851-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26984739

ABSTRACT

BACKGROUND: Previous clinical studies have shown that the circulating level of endostatin is related to kidney injury. We hypothesized that the impact of HbA1c, fasting, and postprandial plasma glucose on urinary albumin excretion would be related to the serum endostatin level. METHODS: A cross-sectional, community-based population study of 1057 Japanese residents was conducted. Of these subjects, 162 with a fasting plasma glucose value between 5.5 and 6.9 mmol/L and an HbA1c level of <6.5 % received an oral glucose tolerance test, had serum endostatin measured, and had the urinary albumin/creatinine ratio (UACR) calculated. RESULTS: In multivariate analysis, 2-h postprandial plasma glucose (ß = 0.26, P < 0.01) was significantly associated with log-transformed UACR, independently of fasting plasma glucose (ß = 0.14, P = 0.28) and HbA1c (ß = -0.08, P = 0.57). When divided by the median value of endostatin (82.2 ng/mL), 2-h postprandial plasma glucose (ß = 0.38, P = 0.01) remained significantly associated with the log-transformed UACR of the participants below the median, while the fasting plasma glucose (ß = 0.34, P = 0.046) was independently associated with the log-transformed UACR of participants above the median. CONCLUSION: Postprandial plasma glucose was independently associated with the urinary albumin excretion of the residents with prediabetes. Moreover, this relationship was limited to residents with a serum endostatin level below the median.


Subject(s)
Albuminuria/blood , Albuminuria/urine , Blood Glucose/metabolism , Endostatins/blood , Prediabetic State/blood , Prediabetic State/urine , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Fasting , Female , Glycated Hemoglobin/metabolism , Humans , Japan , Male , Middle Aged , Postprandial Period
6.
Infect Agent Cancer ; 11: 9, 2016.
Article in English | MEDLINE | ID: mdl-26913058

ABSTRACT

BACKGROUND: Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin. METHODS: This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome. RESULTS: The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR. CONCLUSIONS: Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.

7.
Antiviral Res ; 126: 35-42, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26692214

ABSTRACT

Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [

Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/physiology , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/therapeutic use , Viral Nonstructural Proteins/antagonists & inhibitors , Aged , Drug Therapy, Combination , Female , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/immunology , Real-Time Polymerase Chain Reaction/methods , Treatment Outcome
8.
Metabolism ; 64(6): 698-705, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25817605

ABSTRACT

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.


Subject(s)
Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Serum Albumin/analysis , Adult , Aged , Anthropometry , Asian People , Blood Glucose/analysis , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Female , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Glycation End Products, Advanced , Humans , Male , Middle Aged , Reference Values , Risk Factors , Young Adult , Glycated Serum Albumin
9.
World J Gastroenterol ; 21(7): 2116-23, 2015 Feb 21.
Article in English | MEDLINE | ID: mdl-25717246

ABSTRACT

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, ß2-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.


Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/adverse effects , Hepatitis B, Chronic/drug therapy , Kidney Diseases/chemically induced , Kidney Tubules, Proximal/drug effects , Organophosphonates/adverse effects , Adenine/adverse effects , Adult , Age Factors , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Genetic Predisposition to Disease , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/epidemiology , Humans , Japan/epidemiology , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Kidney Diseases/genetics , Kidney Diseases/physiopathology , Kidney Tubules, Proximal/physiopathology , Logistic Models , Male , Middle Aged , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Odds Ratio , Organic Anion Transport Protein 1/genetics , Osteomalacia/chemically induced , Osteomalacia/epidemiology , Polymorphism, Single Nucleotide , Prevalence , Retrospective Studies , Risk Factors , Time Factors
10.
Antivir Ther ; 20(2): 185-92, 2015.
Article in English | MEDLINE | ID: mdl-24941012

ABSTRACT

BACKGROUND: Liver fibrosis remains one of the most important predictors of sustained virological response (SVR) in this era of direct-acting antiviral treatment of chronic hepatitis C. We compare non-invasive fibrosis assessment with liver biopsy (METAVIR) in terms of their ability to predict SVR by telaprevir (TVR)-based triple therapy. METHODS: This prospective study consisted of 108 patients with chronic HCV genotype 1 infection who received TVR in combination with pegylated interferon (PEG-IFN)-α2b and ribavirin (RBV). Non-invasive fibrosis data included transient elastography (FibroScan), FIB-4 index and aspartate aminotransferase to platelet ratio index (APRI). RESULTS: SVR was achieved by 84.3% of the patients by intention-to-treat analysis. In contrast to the high SVR rates for treatment-naive patients (87.1%, 27 of 31) and patients who previously relapsed (97.9%, 46 of 47), the SVR rate of prior partial/null responders was significantly lower (60.0%, 18 of 30). The impact of fibrosis on SVR was greater for prior partial/null responders, and fibrosis data, including both METAVIR score and non-invasive fibrosis assessments, were useful for predicting SVR. The METAVIR score (area under the receiver operating characteristic curve [AUROC] 0.91, cutoff ≤F2), FibroScan values (AUROC 0.99, cutoff ≤10.0 kPa), FIB-4 index (AUROC 0.91, cutoff ≤3.5) and APRI (AUROC 0.91, cutoff ≤0.80) were shown to have equal, excellent predictive power. CONCLUSIONS: An alternative to METAVIR score by liver biopsy, non-invasive fibrosis assessments are useful options for predicting SVR by prior partial or null responders in TVR-based triple therapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Viral Load/drug effects , Aged , Area Under Curve , Aspartate Aminotransferases/blood , Biomarkers/analysis , Biopsy , Drug Therapy, Combination , Elasticity Imaging Techniques , Female , Hepacivirus/physiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/pathology , Humans , Interferon-alpha/therapeutic use , Liver/drug effects , Liver/pathology , Liver/virology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Male , Middle Aged , Oligopeptides/therapeutic use , Platelet Count , Polyethylene Glycols/therapeutic use , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Treatment Outcome
11.
Diabetes Res Clin Pract ; 103(1): 88-96, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24377833

ABSTRACT

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.


Subject(s)
Biomarkers/urine , Glucose Intolerance/diagnosis , Inositol/urine , Vitamin B Complex/urine , Adult , Aged , Blood Glucose/analysis , Cross-Sectional Studies , Female , Glucose Intolerance/epidemiology , Glucose Intolerance/urine , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Hyperglycemia/urine , Japan/epidemiology , Male , Middle Aged , ROC Curve
12.
Atherosclerosis ; 231(2): 238-45, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24267234

ABSTRACT

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.


Subject(s)
Cholesterol/blood , Lipoproteins/blood , Triglycerides/blood , Adult , Aged , Chromatography, High Pressure Liquid , Female , Healthy Volunteers , Humans , Japan , Male , Menopause , Middle Aged , Particle Size , Reference Values , Sex Factors
13.
Arch Virol ; 158(12): 2465-72, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23775357

ABSTRACT

Human parvovirus B19 infection occurs by droplet nuclei through the respiratory tract and causes a wide range of diseases. It can be transmitted through blood transfusion from asymptomatic blood donors. This study was done to investigate the parvovirus B19 infection rate of a group of healthy Japanese residents. Of 2,081 blood samples tested, 15 (0.72 %) were positive for parvovirus B19 IgM, 1,412 (67.9 %) for B19 virus IgG, and 4 (0.2 %) for parvovirus B19 DNA. About half of all women of childbearing age were susceptible to parvovirus B19 infection. No relationship was found between the frequency of symptoms and the prevalence of parvovirus B19 IgG and IgM, suggesting that there are asymptomatic carriers in the healthy Japanese population. There is a risk of parvovirus B19 infection by blood transfusion from asymptomatic donors and that pregnant women are at high risk for parvovirus B19 infection.


Subject(s)
Parvoviridae Infections/epidemiology , Parvoviridae Infections/virology , Parvovirus B19, Human/isolation & purification , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Carrier State/epidemiology , Carrier State/virology , DNA, Viral/blood , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Japan/epidemiology , Male , Middle Aged , Prevalence , Young Adult
14.
Endocrine ; 43(3): 635-42, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23001602

ABSTRACT

The elevated serum undercarboxylated osteocalcin (ucOC) level is related to osteoporosis. In Japan, vitamin K intake is lower, and the incidence of hip fractures noticeably higher in northern Kyushu than in other areas. The study was done to determine the serum ucOC levels in a Japanese population and its association with diet and glucose metabolism. The data of 3,658 healthy adults aged 40-69 (1,373 men and 2,285 women) who lived in northern Kyushu area were analyzed. The data included anthropometric measurements and a self-reported personal interview on daily intake of foods. The serum ucOC level of each participant was measured by electrochemiluminescence immunoassay. Glycohemoglobin A1c (HbA1c), fasting plasma glucose, and serum insulin concentrations were measured. The median serum ucOC level of the women (4.65 ng/mL) was significantly higher than that of the men (3.04 ng/mL) (P = 0.0021). The age-specific ucOC levels of the men decreased significantly with age. In contrast, the ucOC levels of the women aged ≥50 were elevated, but the levels varied markedly within the other age groups. For both men and women, multivariate analysis identified a daily diet rich in vitamin K and HbA1c level as independently having a significant, negative relationship to serum ucOC level. Our study indicates that the serum ucOC decreases with age in men, increases postmenopausally in women, and correlates inversely with dietary consumption of certain foods and with fasting glucose and HbA1c level.


Subject(s)
Diet , Life Style , Osteocalcin/blood , Adult , Age Factors , Aged , Asian People , Blood Glucose , Cross-Sectional Studies , Female , Glycated Hemoglobin/metabolism , Humans , Japan , Male , Middle Aged , Risk Factors , Sex Factors , Surveys and Questionnaires
15.
Endocrine ; 43(1): 200-5, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22581254

ABSTRACT

The association between HCV infection and myocardial disorders remains unclear. This study aimed to assess whether or not HCV infection influences myocardial dysfunction by the use of NT-proBNP, a sensitive marker of myocardial dysfunction. A total of 198 participants [99 patients with chronic HCV infection (aged 46-68 years) and 99 anti-HCV-negative sex and age matched controls] were examined. Serum HCV-RNA level and HCV genotype were tested and liver biopsy was done only for the patient group. The NT-proBNP concentration of the HCV patients (mean 71.6 ± 79.1 pg/ml; median 46.0 pg/ml, range 5.0-400.0) was significantly higher than that of the controls (mean 39.8 ± 24.4 pg/ml; median 35.8 pg/ml, range 7.0-108.0) (P < 0.05). 20.0 % of the HCV patients and 0.6 % of the controls had high NT-proBNP (higher than 125 pg/ml; the single cut off point for patients under 75 years of age) (P < 0.05). Stepwise multiple regression analysis revealed that chronic HCV infection was independently correlated with NT-proBNP level after adjustment for parameters that might influence NT-proBNP (P = 0.005). Our data suggest that chronic HCV infection is associated with increased NT-proBNP, indicating that chronic HCV infection might induce myocardial dysfunction.


Subject(s)
Heart Ventricles/physiopathology , Hepacivirus/isolation & purification , Hepatitis C, Chronic/blood , Myocarditis/etiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Up-Regulation , Ventricular Dysfunction/etiology , Aged , Biomarkers/blood , Biopsy , Cross-Sectional Studies , Female , Heart Ventricles/microbiology , Hepacivirus/classification , Hepacivirus/genetics , Hepacivirus/metabolism , Hepatitis C Antibodies/analysis , Hepatitis C, Chronic/microbiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/physiopathology , Humans , Japan , Liver/microbiology , Liver/pathology , Male , Middle Aged , Molecular Typing , RNA, Viral/blood
16.
J Hepatol ; 57(6): 1186-92, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22889955

ABSTRACT

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.


Subject(s)
Adjuvants, Pharmaceutic/therapeutic use , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Postmenopause , Raloxifene Hydrochloride/therapeutic use , Selective Estrogen Receptor Modulators/therapeutic use , Aged , Female , Genotype , Hepatitis C, Chronic/virology , Humans , Interferon-alpha/therapeutic use , Interferons , Interleukins/genetics , Middle Aged , Polyethylene Glycols/therapeutic use , Prospective Studies , RNA, Viral/analysis , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use
17.
J Hepatol ; 57(3): 534-40, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22613000

ABSTRACT

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.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/genetics , Insulin Resistance , Interferon-alpha/therapeutic use , Interleukins/genetics , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Aged , Area Under Curve , Cohort Studies , Confidence Intervals , Female , Genotype , Hepacivirus/genetics , Homeostasis , Humans , Interferon alpha-2 , Interferons , Male , Middle Aged , Models, Biological , Multivariate Analysis , Odds Ratio , Polymorphism, Single Nucleotide , ROC Curve , Recombinant Proteins/therapeutic use , Treatment Outcome
18.
Gut Liver ; 5(4): 447-53, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22195242

ABSTRACT

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.

19.
Hepatol Res ; 41(12): 1178-88, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21917085

ABSTRACT

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. METHODS: Study 1: Forty-four chronic HBV patients had liver stiffness measured by FibroScan and underwent liver biopsy. Study 2: Group A: 22 patients started NA treatment at entry and FibroScan was done annually for 3 years. Group B: 23 patients started NA treatment prior to pretreatment FibroScan measurement, and FibroScan was done for from 3 to 5 years after the start of NA treatment. RESULTS: Study 1: The FibroScan values were significantly correlated with fibrosis stage (r = 0.672, P < 0.0001). Optimal cutoff of FibroScan values were 6.1 kPa for ≥ F1, 6.3 kPa for ≥ F2, 8.9 kPa for ≥ F3 and 12.0 kPa for F4. Study 2: For Group A, the baseline median FibroScan value was 8.2 kPa. FibroScan values significantly decreased annually for 3 years after the start of NA treatment (6.4 kPa, 5.8 kPa and 5.3 kPa at years 1, 2 and 3, respectively). For Group B, the FibroScan values did not significantly improve over the 3 years after the start of NA treatment. CONCLUSIONS: Liver stiffness, measured by transient elastography, of chronic hepatitis B patients treated with NA showed a rapid decline in the first 3 years followed by a more steady transition for from 3 to 5 years irrespective of long term virological effect.

20.
J Infect Chemother ; 17(6): 737-43, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21528383

ABSTRACT

This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24 weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r = 0.595, P < 0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24 weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Real-Time Polymerase Chain Reaction/methods , Aged , Female , Hepatitis C, Chronic/blood , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Middle Aged , Polyethylene Glycols/therapeutic use , RNA, Viral/blood , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Statistics, Nonparametric , Treatment Outcome , Viral Load/drug effects , Viral Load/methods
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