Publications (9)34.82 Total impact
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Article: Amino acid substitution in the core protein has no impact on relapse in hepatitis C genotype 1 patients treated with peginterferon and ribavirin.
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ABSTRACT: Previous reports demonstrated that amino acid (aa) substitutions in the hepatitis C virus (HCV) core protein are predictors of non-virological responses to pegylated interferon (Peg-IFN) and ribavirin combination therapy. The aim of this study was to investigate the impact of core aa substitutions on viral kinetics during the treatment and relapse after the treatment. The 187 patients with HCV genotype 1 enrolled in this study were categorized into four groups according to core aa substitution patterns: double-wild group (n=92), Arg70/Leu91; 70-mutant group (n=42), Gln70/Leu91; 91-mutant group (n=31), Arg70/Met91; and double-mutant group (n=22), Gln70/Met91. The relationship between the core aa substitutions and the virological response was examined. Multivariate logistic regression analyses showed that substitution at aa 70 was significantly associated with a poor virological response during the first 12 weeks (decline of <1 log from baseline at week 4, <2 log at week 12), and substitution at aa 91 was significantly associated with detectable HCV RNA at week 24. With respect to relapse, only the ribavirin exposure (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.60-0.98) and HCV RNA disappearance between weeks 13 and 24 (OR, 23.69; 95% CI, 5.44-103.08) were associated independently with relapse, with no correlation being found with the core aa substitutions and relapse. In conclusion, the results showed that core aa substitutions can be strong predictive factors at pretreatment of the non-response, but not for relapse, for virological responders with HCV RNA disappearance during treatment.Journal of Medical Virology 03/2011; 83(3):419-27. · 2.82 Impact Factor -
Article: [A case of granulocyte colony-stimulating factor-producing adenosquamous carcinoma of the liver accompanied by an adenocarcinoma of the ascending colon and urothelial carcinoma of the urinary bladder].
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ABSTRACT: An 83-year-old man was admitted with renal dysfunction, anemia, and peripheral leukocytosis. His peripheral leukocyte count was 41000/µl. A computed tomography scan revealed a solid cystic mass in the liver, mural thickening in the ascending colon and nodules in the right lower lung field. Colonoscopy revealed ascending colon cancer, and analysis of the biopsy specimens revealed well-differentiated adenocarcinoma. However, although a liver abscess was suspected, pus and bacteria were not found in the cystic lesion of the liver mass, the solid lesion of the mass was diagnosed as carcinoma. The serum concentration of granulocyte colony-stimulating factor (G-CSF) was elevated to 256 pg/ml. Because his general condition worsened, we could not treat these tumors, but he died 38 days after admission. Autopsy revealed adenosquamous carcinoma of the liver, well-differentiated adenocarcinoma of the ascending colon, urothelial carcinoma of the urinary bladder, and metastatic squamous cell carcinoma of the lung. Immunohistochemical analysis revealed positive staining for G-CSF in the liver tumor sample.Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 02/2011; 108(2):259-66. -
Article: Multiple cytokine profiling of the therapeutic responses to ribavirin and pegylated interferon-alpha2b using an "induction" approach with natural interferon-beta in difficult-to-treat chronic hepatitis C.
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ABSTRACT: Cyclic and periodic IFN treatment (CPIT) consisting of induction treatment with nIFN-beta followed by maintenance treatment with IFN-alpha could prevent viral breakthrough and achieve rapid virological response (RVR) and early virological response (EVR) in chronic hepatitis C (CHC). The efficacy and immune response of RBV+PEG-IFN-alpha2b using induction approach with CPIT (novel combination treatment: NCT) in 7 CHC patients with genotype 1b and high viral load were evaluated. A biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effect. RVR and EVR were 7/7 and 7/7, respectively. Viral titers dropped below detectable levels in five patients with sustained virological response (SVR) before the end of CPIT (early virological responder: EAVR), and two patients without SVR after the end of CPIT (late virological responder: LAVR). At baseline, in EAVR compared with the controls, IL-6 and IL-15, CXCL-8 and CXCL-10 levels were significantly higher (P < 0.05); IL-10 and IL-13 levels were significantly lower (P < 0.05); and the IL-12 level was lower. In LAVR, GM-CSF, CXCL-8 and CXCL-10, and CCL-4 levels were significantly higher (P < 0.05); and IL-10 and IL-12 were lower than the controls. In EAVR but not LAVR, the IL-12 increased and the CCXL-8 decreased significantly (P < 0.05). In conclusion, NCT-induced viral clearance leading to improvement in the innate immune response resulting in SVR in CHC with genotype 1b and high viral load.Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 07/2009; 29(6):353-68. · 1.63 Impact Factor -
Article: Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C.
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ABSTRACT: The aim of this study was to examine the factors correlated with the progression of ribavirin-induced hemolytic anemia in patients with chronic hepatitis C treated by interferon and ribavirin combination therapy. This study was conducted on 505 patients by the Osaka Liver Disease Study Group. A decline of hemoglobin (Hb) concentration by 2 g/dl at the end of 2 weeks from the start of the treatment ("2 by 2" standard) was adopted as a predictive factor for progression to severe anemia. The ribavirin apparent clearance (CL/F) was also examined. Of 482 patients whose Hb value was more than 12 g/dl before the treatment, 68 patients (14%) had to discontinue ribavirin owing to severe anemia. Patients in the "2 by 2"-positive group (Hb decline over 2 g/dl) and the group with lower CL/F were significantly more likely to discontinue ribavirin owing to severe anemia. Discontinuation was more common among patients aged 60 years or older than for those under 60 years old (21% vs. 9%, P < 0.001). Among patients aged 60 years or older, only the "2 by 2" standard was significantly associated with the discontinuance of ribavirin owing to severe anemia in a multivariate analysis (odds ratio, 4.18; P < 0.001). The "2 by 2" standard of Hb decline can be used to identify patients likely to develop severe anemia. The early reduction of ribavirin can help prevent progression to severe anemia, thus allowing ribavirin therapy to be completed even in older patients.Journal of Gastroenterology 10/2006; 41(9):862-72. · 4.16 Impact Factor -
Article: Should aged patients with chronic hepatitis C be treated with interferon and ribavirin combination therapy?
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ABSTRACT: The aim of this study was to investigate the efficacy and safety of combination therapy of interferon and ribavirin for aged patients with chronic hepatitis C. This study was conducted at Osaka University Hospital and institutions participating in the Osaka Liver Disease Study Group on 329 patients with chronic hepatitis C receiving interferon and ribavirin combination therapy (group A, under 60 year old, n=199; group B, 60-64 year old, n=64; group C, over 65 year old (mean age, 67.8+/-2.2 year old, n=66)). Of the 293 patients who were tested for HCV serotype and HCV viral loads, 215 had HCV-RNA with serotype 1 and high viral loads (1H) and the other 78 had HCV-RNA with serotype 2 or low viral loads (non-1H). In per-protocol analysis, the overall SVR rate of 1H patients was 28% (51/184). Among the 1H patients, the SVR rate was significantly lower in group C (16%) and group B (17%) than in group A (34%) (p<0.05). The overall SVR rate of non-1H patients was 85% (57/67). No significant difference was found in the SVR rate among group C (79%), group B (100%), and group A (84%). On the other hand, the discontinuance of both drugs due to side effects was 29% (19/66) in group C, 20% (13/64) in group B, and 11% (21/199) in group A, with the discontinuance rates being higher in the older group (p=0.002). In aged chronic hepatitis C patients, interferon and ribavirin combination therapy can be recommended for the non-1H patients who showed a high SVR rate of approximately 65%, but not for the 1H patients.Hepatology Research 07/2006; 35(3):185-9. · 2.20 Impact Factor -
Article: Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis.
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ABSTRACT: The aim of this study was to evaluate whether oral glucose tolerance test (OGTT) was useful in evaluating the prognosis of patients with liver cirrhosis. Fifty-six patients with liver cirrhosis were enrolled in a prospective cohort study. In all cases, glucose tolerance was diagnosed by a 75-g OGTT according to World Health Organization (WHO) criteria. The relationship of clinical variables to the cirrhosis-related prognosis was investigated using univariate and multivariate regression models. Diabetes mellitus (DM) was diagnosed in 21 subjects (38%), impaired glucose tolerance (IGT) in 13 subjects (23%), and normal glucose tolerance (NGT) in 22 subjects (39%) using OGTT. The cumulative survival rates of patients with liver cirrhosis and NGT were 94.7% at 5 yr; liver cirrhosis and IGT, 68.8% at 5 yr; liver cirrhosis and DM, 56.6% at 5 yr. The survival rates of patients with liver cirrhosis and DM significantly differed from those with NGT. Univariate analysis demonstrated that serum albumin, total bilirubin, prothrombin activity, Child-Pugh scores, and glucose intolerance were highly significant prognostic factors. Multiple regression analysis yielded albumin and DM as the most powerful independent negative predictors of survival. OGTT appears to be useful for evaluating the prognosis of cirrhotic patients.The American Journal of Gastroenterology 02/2006; 101(1):70-5. · 7.28 Impact Factor -
Article: Expression of X protein and hepatitis B virus replication in chronic hepatitis
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ABSTRACT: The X protein can act on the enhancer of hepatitis B virus in an in vitro system and elevate the transcriptional level of hepatitis B virus. However, because no relationship had been reported between X protein expression and hepatitis B virus replication in patients with chronic hepatitis B, we focused on its expression in the liver in comparison with markers of hepatitis B virus replication. Liver biopsy samples and sera from 59 carriers with HBsAg were examined immunohistochemically for X protein using rabbit IgG against recombinant X protein. There was a significant difference in the serum hepatitis B virus DNA level between X protein–positive and –negative patients (p < 0.001). Serum pre-S1 and pre-S2 antigens were also measured quantitatively by enzyme immunoassay using monoclonal antibodies specific against each antigen. The titers of pre-S1 antigen in patients positive for X protein were significantly higher (p < 0.001) than those of the X protein–negative patients (3.02 ± 0.99 vs. 2.00 ± 0.59, respectively). Similarly, the titers of pre-S2 antigen were 2.98 ± 0.91 vs. 1.94 ± 0.54, respectively (p < 0.001). The rate of positivity of the X protein was higher (38 of 49; 77.6%) in the replicative group (serum HBeAg, serum hepatitis B virus DNA or HBcAg in liver positive) compared with that observed in the nonreplicative group (3 of 10; 30% – serum HBeAg, serum hepatitis B virus DNA and HBcAg in liver negative) (p < 0.01). Our findings indicate that the X protein is closely correlated with hepatitis B virus replication and may have an important role in viral replication in chronic hepatitis B virus infection. (HEPATOLOGY 1991;13:417–421.)Hepatology 12/2005; 13(3):417 - 421. · 11.66 Impact Factor -
Article: The significance of interferon and ribavirin combination therapy followed by interferon monotherapy for patients with chronic hepatitis C in Japan.
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ABSTRACT: One hundred seventy-one patients with chronic hepatitis C were included in this study (genotype1 and high viral loads (1H), [Formula: see text]; non-1H, [Formula: see text]; N.D., [Formula: see text] ). The combination therapy of interferon and ribavirin for 24 weeks with an additional 24 weeks of interferon monotherapy (48-week treatment) was undergone by 42 1H patients and 5 non-1H patients. The combination therapy of interferon and ribavirin was administered for 24 weeks in 67 1H patients and 22 non-1H patients. Among the 1H patients, the HCV relapse rate was significantly higher in those receiving 24-week combination treatment than in those receiving 48-week treatment (78% versus 42%, [Formula: see text] ). Among the non-1H patients, no significant difference was found between them. Sustained virological response (SVR) rates were observed to decrease as the timing of HCV RNA disappearance was delayed. In spite of the small rate (16%), SVR was obtained from the patients who became negative for HCV RNA by week 24 (beyond week 12) only in those receiving 48-week treatment. In 1H patients, 24-week combination treatment followed by interferon monotherapy for 24 weeks was concluded to be the treatment offering the most hope among those that the medical insurance can be applied in Japan.Hepatology Research 08/2004; 29(3):142-147. · 2.20 Impact Factor -
Article: Gastroesophageal reflux disease related to diabetes: Analysis of 241 cases with type 2 diabetes mellitus.
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ABSTRACT: We examined the incidence of symptomatic gastroesophageal reflux disease (GERD) in patients with type 2 diabetes mellitus (DM). Patients comprised those with DM or chronic hepatitis C (CHC) who visited Osaka Prefectural General Hospital in the same study period. Reflux symptoms were examined using a self-administered questionnaire. A total score of 4 or more was considered an indication of symptomatic GERD. Disease duration, hemoglobinA1c and diabetic complications were assessed. Patients with DM (n=241) or CHC (n=42) were recruited for the study. Of the 241 patients with DM, 100 (41.5%) reported experiencing upper gastrointestinal symptoms, whereas only 9 of 42 (21.4%) patients with CHC reported upper gastrointestinal symptoms (P=0.0137). Sixty-one patients (25.3%) with DM had reflux symptoms but only four patients (9.5%) with CHC reported reflux symptoms. The incidence of symptomatic GERD was significantly higher in patients with DM than in those with CHC (P=0.0219). Patients with DM for less than 5 years had a 2.4-fold higher incidence of GERD than patients with CHC. The incidence tended to rise with increased disease duration. Patients with diabetic complications reported reflux symptoms more frequently. The incidence decreased, however, in DM patients who had these conditions for more than 16 years. Type 2 diabetes mellitus is a risk factor for symptomatic GERD. In DM patients, use of oral hypoglycemic agents, body mass index, disease duration and the quality of diabetic control influenced the incidence of GERD.Journal of Gastroenterology and Hepatology 04/2004; 19(3):258-65. · 2.87 Impact Factor
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2005–2011
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Osaka City University
Ōsaka-shi, Osaka-fu, Japan
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