Takayoshi Ito

Showa University, Shinagawa, Tōkyō, Japan

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Publications (25)60.1 Total impact

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    ABSTRACT: Laparoscopic cholecystectomy has become the gold standard for the treatment of cholelithiasis, and many reports of single-incision laparoscopic cholecystectomy have been published in the past few years. Situs inversus totalis is a very rare condition, but the variant anatomy should not preclude a minimally invasive approach to surgery. We report a case of successful single-port laparoscopic cholecystectomy in a patient with situs inversus totalis, describe the technical advantages, and review the literature. © 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.
    No preview · Article · Aug 2015 · Asian Journal of Endoscopic Surgery
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    ABSTRACT: Hepatitis viruses are causative agents for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. However these viruses are also associated with lymphoproliferative disorders (LPDs), such as essential mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma. Indeed, hepatitis C virus infection has been confirmed to be associated with LPDs, but the pathogenic mechanism remains unclear. In this study, we investigated the relationship between hepatitis B virus (HBV) infection and LPDs in 84 patients with chronic hepatitis B (CH-B). LPD markers, such as cryoglobulinemia, high levels of rheumatoid factor (RF), hypocomplementemia, and B cell clonality, were measured and analyzed along with viral factors. Results showed that high levels of RF were observed in 39.5% of patients with CH-B. These high RF levels were not associated with abnormal levels of other LPD markers, but only with the presence of HBV DNA in the sera of these patients. Undergoing therapy with nucleotide analogues was also associated with high RF. In two patients with CH-B, decreasing levels of RF were observed during antiviral therapy. In conclusion, high RF levels are associated with HBV viremia in patients with CH-B. HBV infection also plays an important role in the genesis of LPDs in patients with viral hepatitis.
    No preview · Article · Jan 2014
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    ABSTRACT: The patient was a 63-year-old male, who was treated with the a1a selective blocker (Silodosin 8 mg) and the herbal medicine (Tsumura Hachimijiogan® 7.5 g) for benign prostatic hyperplasia at clinic of the previous doctor. He was aware of the brown urine on the 14-day after beginning of the treatment. Laboratory data on the 27-day showed severe liver injury (T.Bil 10.6 mg/dZ, AST 2,707 IU/L, and ALT 3,035 IU/L), then the patient was admit­ted in our hospital Negative for markers of hepatitis virus, autoimmune liver diseases, no history of heavy drinking strongly speculated the drug-induced liver injury. Even after cessation of the two drugs for one week, the patient was diagnosed as the severe acute hepatitis because of appearance for hepatic encephalopathy, prolona- gation of prothrombin time (40%), and persistence of high levels of transaminase. Then the immune suppressive treatment with 40 mg/day of prednisolone was started. The liver injury was gradually recovered after the treatment, the prednisolone was reduced and finally withdrawed. The DLST showed silodosin was positive, and the JDDW score of drug-induced liver injury showed 8 points These results together indicated that this patient was diagnosed as having the drug-induced liver injury. Here we reported a rare case of drug-induced liver in­jury caused by silodosin.
    No preview · Article · Jan 2014 · Kanzo
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    ABSTRACT: Cyclooxygenase (COX)-2 is involved in inflammation, anti-apoptosis and carcinogenesis. The -1195GG genotype of single nucleotide polymorphism (SNP) in COX-2 promoter was associated with low platelet counts in patients with chronic hepatitis C. Polymorphism of patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene (rs738409 C>G) have been reported to be associated with cirrhosis, and the major genotype of SNPs near interleukin (IL)28B are related to viral clearance. The present study was designed to assess the contribution of these SNPs to disease progression in patients with chronic hepatitis C. The study enrolled 220 Japanese patients with chronic hepatitis C. Three SNPs, -1195 COX-2, PNPLA3 and IL28B (rs8099917), were genotyped in order to analyze their association with hepatic fibrosis and inflammation. The -1195GG genotype in COX-2 was associated with advanced fibrosis and higher levels of inflammation in the liver tissues. The major genotype of IL28B was also associated with advanced fibrosis, but the polymorphism of PNPLA3 was neither associated with fibrosis nor inflammation. Multivariate analysis showed that -1195GG in COX-2 is an independent factor associated with advanced fibrosis, while the major genotype of IL28B and HCV genotype 2 were other independent factors. In conclusion, the -1195GG genotype in COX-2 is a genetic marker for liver disease progression, while the PNPLA3 genotypes are not associated with disease progression in Japanese patients with chronic hepatitis C.
    No preview · Article · Sep 2012 · Journal of Viral Hepatitis

  • No preview · Article · May 2011 · Nippon rinsho. Japanese journal of clinical medicine
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    ABSTRACT: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders. HCV infection of B cells is a predictive factor for lymphoproliferative disorders in patients with chronic hepatitis C, although its molecular mechanisms remain unknown. Epstein-Barr virus (EBV) is a B cell-tropic virus with the potential to cause lymphoproliferative disorders, and its reactivation is induced by several viruses and cytokines. The possibility that HCV infection triggers reactivation of EBV and induces lymphoproliferative disorders were investigated. Expression of EBV mRNAs was analyzed by RT-PCR in patients infected with HCV and control subjects, and correlations between reactivation of EBV and markers for lymphoproliferative disorders were investigated. BZLF1 mRNA, a starter molecule of reactivation, was detected in peripheral blood mononuclear cells from 12 of 52 (23%), patients infected with HCV and the frequency was higher than in healthy subjects [3 of 43 (9%), P = 0.032]. But the presence of the BZLF1 mRNA was not associated with an abnormality of markers for lymphoproliferative disorders. This study on BZLF1 mRNA expression among lymphoid cell subsets showed that reactivation of EBV was observed specifically in B cells. The BZLF1 mRNA disappeared following anti-viral therapy and remained negative after eradication of HCV in patients with a sustained viral response, while the EBER1 RNA, a marker for persistence of EBV, was detected throughout the therapy. Infection with HCV induces reactivation of EBV in B cells, but this reactivation was not associated directly with lymphoproliferative disorders triggered by HCV. J. Med. Virol. 82:2064-2072, 2010. © 2010 Wiley-Liss, Inc.
    No preview · Article · Dec 2010 · Journal of Medical Virology
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    ABSTRACT: We investigated whether tumor-specific CD8(+) T-cell responses affect tumor-free survival as well as the relationship between CD8(+) T-cell responses against tumor-associated antigens (TAAs) and the clinical course after tumor treatment in patients with hepatocellular carcinoma (HCC). Twenty patients with HCC that were treated by radiofrequency ablation or trans-catheter chemo-embolization (TACE) and in whom HCC was undetectable by ultrasonography, CT, and/or MRI 1 month after treatment were enrolled in the study. Before and after treatment for HCC, analyses of TAA (glypican-3, NY-ESO-1, and MAGE-1)-specific CD8(+) T-cell responses were evaluated with an interferon-gamma enzyme-linked immunospot (ELISpot) assay using peripheral CD8(+) T-cells, monocytes, and 104 types of 20-mer synthetic peptide overlapping by 10 residues and spanning the entirety of the 3 TAAs. Sixteen out of 20 patients (80%) showed a positive response (> or = 10 TAA-specific cells/10(5) CD8(+) T-cells) before or after treatment. When we performed univariate analysis of prognostic factors for the tumor-free period in the 20 patients, platelet count, prothrombin time, and the number of TAA-specific CD8(+) T-cells after treatment were significant factors (P = 0.027, 0.030, and 0.004, respectively). In multivariate analysis, the magnitude of the TAA-specific CD8(+) T-cell response (> or = 40 TAA-specific cells/10(5) CD8(+) T-cells) was the only significant prognostic factor for a prolonged tumor-free interval (hazard ratio 0.342, P = 0.022). Our results suggest that strong TAA-specific CD8(+) T-cell responses suppress the recurrence of HCC. Immunotherapy to induce TAA-specific cytotoxic T lymphocytes by means such as the use of peptide vaccines should be considered for clinical application in patients with HCC after local therapy.
    No preview · Article · Nov 2009 · Journal of Gastroenterology
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    ABSTRACT: We present two cases of tuberculous peritonitis with liver cirrhosis complicated by refractory ascites. Case 1 was a 59-year-old female with alcoholic liver cirrhosis. She was admitted to our hospital because of diarrhea, anorexia and inflammatory reactions on a blood test. She had a high fever of 38°C or more and refractory ascites. Tubercle bacilli infection was suspected based on increased levels of serum CA125 and adenosine deaminase (ADA) in ascites. Laparoscopic examination showed white nodules on the peritoneum, and histologic study confirmed tuberculous nodules. The same bacteria were isolated from culture of ascites. Case 2 was a 55-year-old female with hepatitis C virus-infected liver cirrhosis. She was admitted because of high fever and abdominal fullness due to ascites. High levels of serum CA125 and ADA in ascites and ineffectiveness of treatment with antibiotics plus diuretics led us to start anti-tuberculous therapy before definitive diagnosis. Tuberculus bacillus was later isolated from culture of ascites. It is difficult to make early diagnosis of tuberculous peritonitis in cirrhotic patients with ascites due to a lack of specific symptoms. However, determination of serum CA125 and ADA in ascites and the acid-fast bacterial culture of ascites are useful for early diagnosis.
    No preview · Article · Aug 2009 · Clinical Journal of Gastroenterology
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    ABSTRACT: Infection with hepatitis C virus (HCV) is associated with lymphoproliferative disorders, represented by essential mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma, but the pathogenic mechanism remains obscure. HCV may infect B cells or interact with their cell surface receptors, and induce lymphoproliferation. The influence of HCV infection of B cells on the development of lymphoproliferative disorders was evaluated in 75 patients with persistent HCV infection. HCV infection was more prevalent (63% vs. 16%, 14%, or 17% P < 0.05 for each), and HCV RNA levels were higher (3.35 +/- 3.85 vs. 1.75 +/- 2.52, 2.15 +/- 2.94 or 2.10 +/- 2.90 log copies/100 ng, P < 0.01 for each) in B cells than CD4(+), CD8(+) T cells or other cells. Negative-strand HCV RNA, as a marker of viral replication, was detected in B cells from four of the 75 (5%) patients. Markers for lymphoproliferative disorders were more frequent in the 50 patients with chronic hepatitis C than the 32 with chronic hepatitis B, including cryoglobulinemia (26% vs. 0%, P < 0.001), low CH(50) levels (48% vs. 3%, P = 0.012), and the clonality of B cells (12% vs. 0%, P < 0.01). By multivariate analysis, HCV RNA in B cells was an independent factor associated with the presence of at least one marker for lymphoproliferation (odds ratio: 1.98 [95% confidence interval: 1.36-7.24], P = 0.027). Based on the results obtained, the infection of B cells with HCV would play an important role in the development of lymphoproliferative disorders.
    No preview · Article · Apr 2009 · Journal of Medical Virology

  • No preview · Article · Jan 2009
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    ABSTRACT: Aim: We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8+ T-cell responses and the clinical course of acute HCV infection. Methods: Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8+ T-cell responses was performed using an interferon-γ-based enzyme-linked immunospot assay using peripheral CD8+ T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b. Results: Five patients presented detectable HCV-specific CD8+ T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8+ T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8+ T-cells correlated with maximum serum alanine aminotransferase level during the course (r = 0.841, P = 0.036). Conclusions: HCV-specific CD8+ T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8+ T-cell responses, but without development of antibody against HCV.
    No preview · Article · Nov 2008 · Hepatology Research
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    Kazumasa Hiroishi · Takayoshi Ito · Michio Imawari
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    ABSTRACT: Immune responses against hepatitis C virus (HCV) play a crucial role in the pathogenesis of chronic hepatitis C. HCV infection often persists and leads to chronic hepatitis and eventually cirrhosis. Accumulated data suggest that HCV proteins suppress host immune responses through the suppression of functions of immune cells, such as cytotoxic T lymphocytes, natural killer cells, and dendritic cells. They also suppress the type 1 interferon signaling system. The resulting insufficient immune responses against HCV lead to the sustained infection. The appropriate control of immune responses would contribute to the eradication of HCV and the improvement of hepatitis, but there are still many issues to be clarified. This review describes the scientific evidence to support these emerging concepts, and will touch on the implications for improving antiviral therapy.
    Preview · Article · Sep 2008 · Journal of Gastroenterology and Hepatology

  • No preview · Article · Jan 2008
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    ABSTRACT: Aim: Regulatory T cells (Tregs) maintain immunological tolerance and suppress autoreactive immune responses. We evaluated the intrahepatic status of Tregs in patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CH-C), or chronic hepatitis B (CH-B). Methods: We analyzed 85 patients (20 AIH, 22 PBC, 27 CH-C, and 16 CH-B) and 14 controls. Using liver tissue samples obtained by needle biopsy or from marginal parts of resected metastatic liver tumors in the controls, immunohistochemical analyses of forkhead box P3+, which is a specific marker for Tregs, CD4+, and CD8+ cells were performed. Results: Intrahepatic Tregs were significantly more infiltrated in patients with liver diseases than in the controls. There were significantly fewer intrahepatic Tregs in the AIH patients than in the PBC patients (P = 0.037). Patients with alow frequency of intrahepatic Tregs were detected significantly more in the AIH and CH-B groups than in the PBC and CH-C groups (P < 0.05). In addition, the frequency of Tregs decreased in the liver of PBC patients as the pathological stage of the disease advanced. We found significantly less infiltration of CD4+ T cells in AIH than in other diseases (P < 0.05). Liver-infiltrating CD8+ T cells were detected more frequently in the CH-B group than in other groups (P < 0.003). Conclusion: Intrahepatic Tregs were increased in both patients with autoimmune liver diseases and those with viral hepatitis. In autoimmune liver diseases, intrahepatic Tregs were fewer in the AIH patients than in the PBC patients.
    No preview · Article · Nov 2007 · Hepatology Research

  • No preview · Article · Jul 2007 · Nihon Naika Gakkai Zasshi
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    ABSTRACT: HCV RNA has a unique regulatory mechanism for translation. The X region of 3'-UTR and core-coding sequence regulate HCV translation. In this study, we clarified that the entire 3'-UTR also enhances HCV translation, and the envelope-coding sequence of HCV genotype 1b increases degree of this enhancement. In the luciferase reporter assay using rabbit reticulocyte lysates, translational enhancement by 3'-UTR with core to E2 regions was 25-fold higher when compared with control RNA lacking the 3'-UTR. Presence of the entire E2 sequence was important for this enhancement. This phenomenon was not due to transcript stability, and envelope protein alone did not affect translation. E2-coding sequence of genotype 1a had no effect on translation. We observed the same results in animal cell culture systems using bicistronic RNA. Structural protein-coding sequences and 3'-UTR of HCV RNA regulate viral translation, and a target for antiviral agents may be present in these regions.
    Full-text · Article · Mar 2006 · Virology
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    ABSTRACT: Ribavirin-induced hemolytic anemia is one of the important adverse effects for the premature cessation of interferon and ribavirin combination therapy for hepatitis C virus clearance. To elucidate the mechanism of this matter, we examined the effects of plasma and erythrocyte ribavirin concentration on hemoglobin (Hb) reduction to assess hemolytic anemia in this combination therapy. Nineteen patients, treated with the interferon alpha-2b and ribavirin combination therapy, were included. Plasma and erythrocyte ribavirin concentrations were monitored for the first 28 days of the combination therapy, in relation to changes in hematological parameters, Hb and hematocrit values. The initial dose of ribavirin was 11.5+/-1.5mg/kg/day. Steady-state plasma and erythrocyte ribavirin concentrations were 8.9+/-2.6 and 1218+/-270muM, respectively. Significant correlation was observed between erythrocyte ribavirin and Hb reduction (r=0.360, p<0.05), but not between plasma ribavirin and Hb reduction. The patients with higher levels of erythrocyte ribavirin (>/=1000muM) had greater Hb reduction compared to those with lower levels (<1000muM) (3.8+/-1.2g/dL versus 2.6+/-0.9g/dL, p<0.05). Nine cases out of 12 patients who developed anemia within the first 28 days of the combination therapy had higher levels of erythrocyte ribavirin (>/=1000muM). We confirmed that erythrocyte ribavirin was strongly associated with Hb reduction in interferon and ribavirin combination therapy.
    No preview · Article · Jan 2006 · Hepatology Research
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    ABSTRACT: Fifty years old female was admitted due to acute liver injury and diagnosed as having autoimmune hepatitis. She was treated with a high dose of metyhlprednisolone, and recovered from the liver injury. Reduction of steroid led to recurrence of liver injury. Since addition of azathioprine was not effective, we treated her with a high dose of steroid again. During tapering of steroid in the presence of azathioprine, she relapsed again. Because of the use of a large total amount of steroid and difficulty of tapering steroid, we replaced azathioprine with cyclosporine A. After the alteration, she has remained in remission with decreasing amount of steroid. About 10% of patients with autoimmune hepatitis are resistant to the steroid therapy, and there are some responders who cannot continue it due to its adverse effects. Combination therapy with cyclosporine A and a minimal amount of steroid may be useful for such patients.
    No preview · Article · Jan 2005 · Kanzo
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    ABSTRACT: Ribavirin-induced hemolytic anemia is one cause for cessation of combination therapy with alpha interferon 2b and ribavirin for hepatitis C infection. Determining cellular ribavirin levels in blood, including the levels of its phosphorylated metabolites, might be useful for predicting ribavirin-induced anemia, because the metabolites accumulate in erythrocytes. We simplified an assay method developed previously to make it suitable for routine monitoring of cellular ribavirin. Whole blood diluted with a sixfold volume of ice-cold distilled water was subjected to acid phosphatase digestion to convert phosphorylated ribavirin metabolites to free ribavirin. The resulting mixture, spiked with an internal standard, was treated by phenyl boronic acid column extraction, followed by reverse-phase high-performance liquid chromatography analysis. The calibration curve for ribavirin levels in whole blood was linear at concentrations of 5.3 to 1,024 μM (r2 = 0.9999). Validation coefficients of variation for intra- and interday assays were 2.9 to 5.8% and 4.3 to 8.3%, respectively. We tested this method by monitoring blood ribavirin concentrations in two hepatitis C patients receiving alpha interferon 2b-plus-ribavirin combination therapy.
    Full-text · Article · Nov 2004 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: A 71-year-old Japanese male with liver cirrhosis due to hepatitis C virus infection showed a markedly elevated serum α -fetoprotein (AFP) concentration. Computed tomography (CT) revealed a hypervascular tumor compatible with hepatocellular carcinoma (HCC) in Couinaud's segment 4 (S4) in the liver. One month later, the tumor was enlarged and five months later, the serum AFP level began to decrease without any therapy. The tumor in S4 subsequently regressed over two months. Tumor stains were not observed in the S4 area on digital subtraction angiography (DSA) and the serum AFP level had decreased to within normal range. On admission, another hypervascular tumor was visualized in S5 by CT and the lesion was treated with transarterial chemoembolization (TAE) . After TAE treatment, there was no finding of HCC recurrence on CT for at least twenty months. This report describes a case of spontaneous regression of HCC with a second enlarged tumor, which was satisfactorily treated with TAE.
    Preview · Article · Jan 2004

Publication Stats

230 Citations
60.10 Total Impact Points


  • 2001-2012
    • Showa University
      • • Department of Medicine
      • • Division of Gastroenterology
      • • Department of Internal Medicine
      Shinagawa, Tōkyō, Japan