[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) in the interleukin 28B gene (IL28B) are good pretreatment predictors of anti-hepatitis C virus (HCV) therapy with interferon. SNPs of the inosine triphosphatase (ITPA) gene are associated with reduced haemoglobin levels during treatment with ribavirin. The i-densy™ (Arkray, Inc.), which is based on the quenching probe (QP) method, automatically detects target genes in blood samples by fluorescence quenching within 100 min. Using a QP and primer set, a gene amplification response is generated that can quickly and easily detect a specific gene's arrangement by fluorometry. The present study was conducted to compare the utility of i-densy (QP method) with that of conventional direct sequencing (DS) for detecting SNPs in the IL28B and ITPA genes in chronic hepatitis C patients. Between June 2011 and January 2012, 73 consecutive patients underwent genotyping of IL28B, and 54 patients underwent genotyping of ITPA. All of the patients were seropositive for HCV-RNA. The IL28B and ITPA genotypes were tested for bi-allelic polymorphisms in rs8099917 (T/T, T/G and G/G; minor allele, G) and rs1127354 (C/C, C/A and A/A; minor allele, A), respectively. The results obtained with the QP method were identical to those obtained with the conventional DS method. The frequency of the IL28B genotypes TT, GT and GG were 74%, 24.7% and 1.4%, respectively, and those of the ITPA genotypes CC, AC and AA were 68.5%, 29.6% and 1.9%, respectively. These results indicate that the i-densy using the QP method can automatically, quickly and easily identify genotypes of IL28B and ITPA.
Journal of Viral Hepatitis 04/2013; 20(4):e124-e126. · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although it has been reported that hepatitis C virus (HCV) infection is associated with a significant decline in health-related quality of life (HRQOL), the underlying causes and mechanisms are still unknown. Insulin resistance (IR) is recognized as a distinct aspect of chronic HCV infection. Therefore, we attempted to identify the factors including IR indices that are related to the HRQOL of patients with chronic hepatitis C (CHC). METHODS: One hundred and seventy-five CHC patients (91 female, 84 male, mean age, 56.4 years) not using antidiabetic agents were included and underwent a 75-g oral glucose tolerance test (OGTT) and completed a self-administered HRQOL questionnaire, the Short Form 36 (SF-36), which is a well-validated questionnaire for assessing general QOL. Scale scores were standardized and summarized into physical and mental component summary (PCS and MCS). We investigated which clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), were associated with decline in PCS and MCS scores in CHC patients. RESULTS: There were no significant differences in clinical parameters between high and low MCS, but there were significant differences in age, sex, hemoglobin, liver fibrosis, OGTT pattern, and HOMA-IR between high and low PCS. Multivariate analysis showed that HOMA-IR >2 was independently associated with lower PCS (OR 2.92, p < 0.01). CONCLUSIONS: Our results suggest that impairment of HRQOL, especially physical domains, in CHC patients is associated with IR.
Journal of Gastroenterology 03/2013; · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC. Methods We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver biopsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels (≥10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeostasis model assessment for insulin resistance value of ≥2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention. Results A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic inflammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of <15×10(4) /μL, aspartate aminotransferase level of ≥50 IU/L, γ-glutamyl transpeptidase level of ≥35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for insulin resistance and whole-body insulin sensitivity index. Conclusion Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.
Internal Medicine 01/2013; 52(21):2393-400. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The treatment strategy for cases of combined autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a 53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and histological findings revealed that their liver was not cirrhotic but did have chronic damage. The histological findings of both patients were suggestive of AIH. The patients were systematically treated with pegylated interferon-alpha 2b plus ribavirin which was preceded by and combined with corticosteroid (CS), and showed sustained virological responses and normal liver function. Although these two patients with combined AIH and CHC were successfully treated with this regimen, careful attention to exacerbation of hepatic inflammation is needed because hepatitis C viral load was increased due to immunosuppression during CS treatment.
Clinical Journal of Gastroenterology 04/2012; 5(2):141-145.
[Show abstract][Hide abstract] ABSTRACT: Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients.
A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3 ± 10.8 years; 95 females, mean age 56.6 ± 10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy.
Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development.
Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.
Journal of Gastroenterology 02/2011; 46(6):790-8. · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our previous studies have indicated a close association between visceral fat accumulation and hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). This study investigated whether visceral fat accumulation was related to the pathogenesis and disease progression of nonalcoholic steatohepatitis (NASH)/NAFLD.
First, a total of 550 subjects who underwent a health checkup and measurement of visceral fat accumulation, done with a bioelectrical impedance analyzer (X-SCAN; Owa Medical, Fukuoka, Japan), were included. The relationship between visceral fat accumulation and biochemical parameters was examined. Second, a total of 74 patients with NASH/NAFLD who underwent liver biopsy were reviewed. Visceral fat accumulation was determined by abdominal computed tomography. The association between visceral fat accumulation and the histopathological grade/stage determined by the NAFLD activity score and Brunt's classification was evaluated.
There was a significant relationship between visceral fat accumulation and glucose, triglyceride, and alanine aminotransferase (ALT; r = 0.423, P < 0.01). In stepwise regression analysis, visceral fat area (VFA), serum triglyceride level, and serum low-density lipoprotein (LDL)-cholesterol level were selected as predictor variables for serum ALT level, in a continuous manner (serum ALT level = -1.359 + 0.143 × VFA + 0.046 × triglyceride + 0.059 × LDL, R(2) = 0.217, P < 0.001). In patients with NASH, there was no correlation between histological grade and the visceral fat volume. Visceral fat accumulation in patients with stage 3/4 advanced NASH was greater than that in patients with stage 1/2 early NASH (P < 0.05).
These results suggest that visceral fat accumulation plays a role in steatosis and fibrosis in the pathogenesis and prognosis of NAFLD.