Publications (45)155.07 Total impact
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Article: α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C.
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ABSTRACT: The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, the cohort consisted of 1818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, sustained virological response (SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. Cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non- SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pre-treatment levels. Conclusion: Post-IFN treatment ALT and AFP levels are significantly associated with the hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication. (HEPATOLOGY 2013.).Hepatology 04/2013; · 11.66 Impact Factor -
Article: Impaired brain activity in cirrhotic patients with minimal hepatic encephalopathy: evaluation by near infrared spectroscopy.
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ABSTRACT: AIM: Near infrared spectroscopy (NIRS) is a tool that could noninvasively measure the regional cerebral oxygenated hemoglobin (oxy-Hb) concentration with high time resolution. The aim of the present study is to reveal the time-dependent regional cerebral oxy-Hb concentration change coupled with brain activity during task performance in patients with MHE. METHODS: Cerebral oxy-Hb concentration was measured by using NIRS in 29 cirrhotic patients without overt HE. Of those, 16 patients who had abnormal electroencephalography findings were defined as having minimal HE (MHE). Responsive increase in oxy-Hb during a word fluency task was compared between MHE and no-MHE patients. RESULTS: There was no difference in the maximum value of oxy-Hb increase between patients with and without MHE (0.26±0.12 mM mm vs. 0.32±0.22 mM mm, p=0.37). However, the pattern of the time course changes of oxy-Hb was different between 2 groups. The MHE group was characterized by a gradual increase of oxy-Hb throughout the task compared to steep and repetitive increase in no-MHE. Increase in oxy-Hb concentration at 5 seconds after starting the task was significantly small in MHE compared to no-MHE (0.03±0.05 mM mm vs. 0.11 ± 0.09 mM mm, p=0.006). CONCLUSIONS: The cerebral oxygen concentration is poorly reactive in response to task among cirrhotic patients without overt HE but having abnormal electroencephalography findings. These impaired responses in regional cerebral oxy-Hb concentration may be related to the latent impairment of brain activity seen in MHE.Hepatology Research 04/2013; · 2.20 Impact Factor -
Article: Serum HBV RNA as a possible marker of HBV replication in the liver during nucleot(s)ide analogue therapy.
Journal of Gastroenterology 03/2013; · 4.16 Impact Factor -
Article: Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy.
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ABSTRACT: To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma (HCC) and survival after curative treatment. This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation (RFA) therapy. The mean age was 67.6 years and the mean observation period was 4.04 years. The etiological background of liver disease was hepatitis B virus infection in 30, hepatitis C virus infection in 278, excessive alcohol drinking in 9, and other in 27 patients. The Child-Pugh classification grade was A (n = 307) or B (n = 37). The number of HCC nodules was one in 260, two in 61, and three in 23 patients. For surveillance of HCC recurrence after curative therapy with RFA, patients were radiologically evaluated every 3 mo. Factors associated with distant recurrence of HCC or survival were studied. Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant recurrence. The 1-, 2-, and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others: 50.6% vs 26.8%, 83.5% vs 54.4%, and 93.8% vs 73.0%, respectively (P = 0.0001). Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97 (95%CI, 1.33-2.91), (P = 0.0007)] after adjustment for other risk factors, such as number of HCC nodules [2.03 (95%CI, 1.51-2.73), P < 0.0001] and initial level of serum alpha fetoprotein (AFP) [1.43 (95%CI, 1.04-1.97), P = 0.028]. Obesity was not an independent predictor of recurrence. The incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic patients. Among 232 patients who had HCC recurrence, 138 had a second recurrence. The 1-, 2-, and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others: 9.0% vs 5.9%, 53.1% vs 24.3%, and 69.6% vs 42.3%, respectively (P = 0.0021). Inadequate maintenance of blood glucose in diabetic patients [1.99 (95%CI, 1.23-3.22), P = 0.0049] and presence of multiple HCC nodules [1.53 (95%CI, 1.06-2.22), P = 0.024] were again significantly associated with second HCC recurrence. Inadequate maintenance of blood glucose in diabetic patients was also a significant predictor of poor survival [2.77 (95%CI, 1.38-5.57), P = 0.0046] independent of excessive alcohol drinking [6.34 (95%CI, 1.35-29.7), P = 0.019], initial level of serum AFP [3.40 (95%CI, 1.88-6.18), P < 0.0001] and Child-Pugh classification grade B [2.24 (95%CI, 1.12-4.46), P = 0.022]. Comparing diabetic patients with inadequate maintenance of blood glucose vs the others, the 1-, 2-, and 3-year survival rates were significantly lower in diabetic patients with inadequate maintenance of blood glucose: 92% vs 99%, 85% vs 96%, and 70% vs 92%, respectively (P = 0.0003). Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy.World Journal of Gastroenterology 01/2013; 19(2):249-57. · 2.47 Impact Factor -
Article: Early decrease in α-fetoprotein, but not des-γ-carboxy prothrombin, predicts sorafenib efficacy in patients with advanced hepatocellular carcinoma.
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ABSTRACT: The aim of this study was to investigate the relationships between early changes in the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), and antitumor response in the early period following administration of sorafenib in patients with advanced hepatocellular carcinoma (HCC). Forty-eight advanced HCC patients were evaluated. AFP and DCP were measured at baseline, and after 2 and 4 weeks, and the antitumor responses were evaluated according to the RECIST criteria 4 weeks after starting sorafenib therapy. The ratios of each tumor marker were compared by stratifying the patients into the partial response (PR) + stable disease (SD) group or the progressive disease (PD) group. Both 2 and 4 weeks after starting sorafenib therapy, the AFP ratio in the PR + SD group (n = 32) was significantly lower than in the PD group (n = 16; p = 0.002, p = 0.002). DCP was elevated in both the PR + SD group and the PD group 2 weeks and 4 weeks after starting sorafenib therapy. Evaluation of AFP ratios 2 and 4 weeks after starting sorafenib therapy may be useful for predicting antitumor response. On the other hand, early elevation of DCP does not necessarily suggest treatment failure by sorafenib, as DCP elevation can occur despite therapeutic efficacy.Oncology 11/2011; 81(3-4):251-8. · 2.27 Impact Factor -
Article: Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response.
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ABSTRACT: Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.Hepatology 08/2011; 55(1):20-9. · 11.66 Impact Factor -
Article: Changes in hepatitis C viral load during first 14 days can predict the undetectable time point of serum viral load by pegylated interferon and ribavirin therapy
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ABSTRACT: Aim: In the treatment of chronic hepatitis C, pegylated interferon (PEG-IFN) and ribavirin combination therapy must be continued for an adequate duration to improve the rate of sustained virological response. We attempted to predict the time point at which serum hepatitis C virus (HCV) RNA are undetectable during combination therapy.Methods: Patients with HCV genotype 1b were enrolled in a model preparation (n = 35) and a validation group (n = 70). All patients received PEG-IFN-α-2b/ribavirin combination therapy for at least 48 weeks, and serological samples were screened a minimum of 17 times during the therapy. Serum HCV RNA were measured by the Abbott RealTime HCV assay. Using the HCV dynamics model described by Neumann et al., we used multiple linear regression analysis to select factors that affected the undetectable time point.Results: Difference in viral load between weeks 1 and 2 was the only predictive factor for the undetectable time point of serum HCV RNA (r2 = 0.67, P < 0.0005), and we derived the following prediction equation: undetectable time point (week) = 13.495 × (viral load at day 14 [log IU/mL] − viral load at day 7 [log IU/mL]) + 25.456. The equation was applicable to the validation group.Conclusion: We created a formula for predicting the undetectable time point from viral load measurements early in PEG-IFN-α-2b/ribavirin combination therapy. An early response reflects sensitivity to therapy, and the estimation of an undetectable time point would be useful for determining the optimal duration of treatment for chronic hepatitis C patients.Hepatology Research 02/2011; 41(3):217 - 224. · 2.20 Impact Factor -
Article: RIG-I- and MDA5-initiated innate immunity linked with adaptive immunity accelerates beta-cell death in fulminant type 1 diabetes.
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ABSTRACT: The contribution of innate immunity responsible for aggressive β-cell destruction in human fulminant type 1 diabetes is unclear. Islet cell expression of Toll-like receptors (TLRs), cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, downstream innate immune markers, adaptive immune mediators, and apoptotic markers was studied in three autopsied pancreata obtained 2 to 5 days after onset of fulminant type 1 diabetes. RIG-I was strongly expressed in β-cells in all three pancreata infected with enterovirus. Melanoma differentiation-associated gene-5 was hyperexpressed in islet cells, including β- and α-cells. TLR3 and TLR4 were expressed in mononuclear cells that infiltrated islets. Interferon (IFN)-α and IFN-β were strongly expressed in islet cells. Major histocompatibility complex (MHC)-class I, IFN-γ, interleukin-18, and CXC motif ligand 10 were expressed and colocalized in affected islets. CD11c+ MHC-class II+ dendritic cells and macrophage subsets infiltrated most islets and showed remarkable features of phagocytosis of islet cell debris. CD4+ forkhead box P3+ regulatory T cells were not observed in and around the affected islets. Mononuclear cells expressed the Fas ligand and infiltrated most Fas-expressing islets. Retinoic acid-receptor responder 3 and activated caspases 8, 9, and 3 were preferentially expressed in β-cells. Serum levels of IFN-γ were markedly increased in patients with fulminant type 1 diabetes. These findings demonstrate the presence of specific innate immune responses to enterovirus infection connected with enhanced adoptive immune pathways responsible for aggressive β-cell toxicity in fulminant type 1 diabetes.Diabetes 02/2011; 60(3):884-9. · 8.29 Impact Factor -
Article: Relationship between polymorphisms of the inosine triphosphatase gene and anaemia or outcome after treatment with pegylated interferon and ribavirin.
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ABSTRACT: A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in combination with other factors. Genotype 1b chronic hepatitis C patients (n=132) treated with pegylated interferon (PEG-IFN)-α and RBV for 48 weeks were genotyped for ITPA rs1127354 and examined for anaemia and treatment outcome. Variants of the ITPA gene protected against severe anaemia throughout the 48-week treatment period and were associated with lower incidence of anaemia-related RBV dose reduction. A combination of the ITPA genotype with baseline haemoglobin (Hb) and creatinine clearance (CLcr) levels predicted severe anaemia with high accuracy (90% sensitivity and 62% specificity). Among a subset of patients with the IL28B genotype of TT at rs8099917, patients with variants of the ITPA gene were associated with a higher rate of receiving >80% of the expected RBV dose, a higher rate of sustained virological response (SVR), and a lower rate of relapse. The variants of the ITPA gene, which could protect against haemolytic anaemia and RBV dose reduction, were associated with a high rate of SVR by standard PEG-IFN and RBV therapy in a subset of Japanese patients with the favourable TT genotype at rs8099917 of IL28B. A combination of ITPA genetic polymorphisms with baseline Hb and CLcr levels further improves the predictive accuracy of severe anaemia.Antiviral therapy 01/2011; 16(5):685-94. · 3.16 Impact Factor -
Article: Expression of keratin 19 is related to high recurrence of hepatocellular carcinoma after radiofrequency ablation.
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ABSTRACT: Keratin (K) 19 positivity has been reported to be a useful predictive marker for recurrence in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection. We investigated the clinical usefulness of K19 positivity in patients who had received curative radiofrequency ablation (RFA). We retrospectively evaluated the clinicopathological features, including imaging and K19 expression, in 246 patients with HCC who were within the Milan criteria and had received curative RFA. Using a two-step insertion method, tumor biopsies were obtained just prior to RFA and were evaluated histologically. Tumor seeding due to liver biopsy and RFA was not observed. Ten patients (4.1%) had K19-positive HCC. Imaging findings were similar between K19-positive and -negative HCC (p = 0.187). Nine out of 10 patients (90%) who had K19-positive HCC had recurrence of HCC after RFA, and intrahepatic recurrences were observed within 12 months in 6 out of 10 (60.0%). K19 positivity was a significant risk factor for recurrence (p < 0.0001) and early recurrence (<1 year after RFA; p =0.012). K19 expression (p = 0.016) was an independent risk factor for tumor status exceeding the Milan criteria after RFA. Expression of K19 is related to high recurrence of HCC after curative RFA.Oncology 01/2011; 80(3-4):278-88. · 2.27 Impact Factor -
Article: Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection.
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ABSTRACT: An increase in the aging population is an impending problem. A large cohort study was carried out to determine the influence of aging and other factors on hepatocarcinogenesis in patients treated with interferon. Biopsy-proven 2547 chronic hepatitis C patients registered at our referral center since 1992 were included. Of these, 2166 were treated with interferon-based therapy. Incidences of hepatocellular carcinoma (HCC) associated with interferon were analyzed by Kaplan-Meier and person-years methods for an average follow-up of 7.5 years. Factors associated with HCC risk were determined by Cox proportional hazard analysis. HCC developed in 177 interferon-treated patients. The risk for HCC depended on age at primary biopsy and increased more than 15-fold after 65 years of age. Even when stratified by stage of fibrosis, the cumulative and annual incidences of HCC were significantly higher in older patients than in younger patients (P < 0.001) at the same stage of fibrosis, except for cirrhosis. Progression of fibrosis over time was significantly accelerated in older patients. The impact of viral eradication on HCC prevention was less significant in older patients than in younger patients. Multivariate analysis confirmed that age, gender, liver fibrosis, liver steatosis, total cholesterol level, fasting blood sugar level, baseline and postinterferon alpha-fetoprotein level, and virological response to interferon were independent risk factors associated with HCC. Aging was the strongest risk factor for a nonvirological response to interferon-based antiviral therapy. Conclusion: Elderly patients are at a higher risk for HCC. Hepatitis C viral eradication had a smaller effect on hepatocarcinogenesis in older patients. Patients should therefore be identified at an earlier age and treatment should be initiated.Hepatology 08/2010; 52(2):518-27. · 11.66 Impact Factor -
Article: A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification and regression tree analysis.
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ABSTRACT: Aim: Early disappearance of serum hepatitis C virus (HCV) RNA is the prerequisite for achieving sustained virological response (SVR) in peg-interferon (PEG-IFN) plus ribavirin (RBV) therapy for chronic hepatitis C. This study aimed to develop a decision tree model for the pre-treatment prediction of response. Methods: Genotype 1b chronic hepatitis C treated with PEG-IFN alpha-2b and RBV were studied. Predictive factors of rapid or complete early virological response (RVR/cEVR) were explored in 400 consecutive patients using a recursive partitioning analysis, referred to as classification and regression tree (CART) and validated. Results: CART analysis identified hepatic steatosis (<30%) as the first predictor of response followed by low-density-lipoprotein cholesterol (LDL-C) (>/=100 mg/dL), age (<50 and <60 years), blood sugar (<120 mg/dL), and gamma-glutamyltransferase (GGT) (<40 IU/L) and built decision tree model. The model consisted of seven groups with variable response rates from low (15%) to high (77%). The reproducibility of the model was confirmed by the independent validation group (r(2) = 0.987). When reconstructed into three groups, the rate of RVR/cEVR was 16% for low probability group, 46% for intermediate probability group and 75% for high probability group. Conclusions: A decision tree model that includes hepatic steatosis, LDL-C, age, blood sugar, and GGT may be useful for the prediction of response before PEG-IFN plus RBV therapy, and has the potential to support clinical decisions in selecting patients for therapy and may provide a rationale for treating metabolic factors to improve the efficacy of antiviral therapy.Hepatology Research 04/2010; 40(4):251-60. · 2.20 Impact Factor -
Article: Small invasive ductal adenocarcinoma of the pancreas associated with lymphoplasmacytic sclerosing pancreatitis.
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ABSTRACT: An asymptomatic 59-year-old man underwent pancreatoduodenectomy for a pancreatic mass that was discovered during a health check-up. Histopathology indicated typical features of lymphoplasmacytic sclerosing pancreatitis (LPSP) or autoimmune pancreatitis along with the presence of abundant IgG4-positive plasma cells throughout the mass. A small invasive ductal adenocarcinoma was observed in the center of the area affected by LPSP. The present case suggests that LPSP may be closely related to carcinogenesis of the pancreas.Pathology International 10/2009; 59(10):744-7. · 1.62 Impact Factor -
Article: Reproducibility and usability of chronic virus infection model using agent-based simulation; comparing with a mathematical model.
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ABSTRACT: We created agent-based models that visually simulate conditions of chronic viral infections using two software. The results from two models were consistent, when they have same parameters during the actual simulation. The simulation results comprise a transient phase and an equilibrium phase, and unlike the mathematical model, virus count transit smoothly to the equilibrium phase without overshooting which correlates with actual biology in vivo of certain viruses. We investigated the effects caused by varying all the parameters included in concept; increasing virus lifespan, uninfected cell lifespan, uninfected cell regeneration rate, virus production count from infected cells, and infection rate had positive effects to the virus count during the equilibrium period, whereas increasing the latent period, the lifespan-shortening ratio for infected cells, and the cell cycle speed had negative effects. Virus count at the start did not influence the equilibrium conditions, but it influenced the infection development rate. The space size had no intrinsic effect on the equilibrium period, but virus count maximized when the virus moving speed was twice the space size. These agent-based simulation models reproducibly provide a visual representation of the disease, and enable a simulation that encompasses parameters those are difficult to account for in a mathematical model.Bio Systems 09/2009; 99(1):70-8. · 1.27 Impact Factor -
Article: [Epithelioid hemangioendothelioma of the liver diagnosed by laparoscopy guided biopsy].
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ABSTRACT: A 35-year-old woman was admitted to our hospital for right upper quadrant pain and multiple liver tumor were detected by diagnostic imaging. Tumors located near the surface of the liver which accompanied capsular retraction. Diagnostic laparoscopy showed multiple white tone tumors with retraction of the adjacent liver capsule. Tumor targeted biopsy was performed. The pathologic diagnosis of epithelioid hemangioendothelioma (EHE) was made by the positive staining of factor VIII-related antigen. EHE tend to locate in peripheral and extend to the liver capsule. Therefore, we face difficulties in getting biopsy sample safely. Here we report a useful case of laparoscopic examination and biopsy in the diagnosis of EHE.Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 12/2008; 105(11):1640-7. -
Article: Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response.
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ABSTRACT: Clinical significance of molecules involving innate immunity in treatment response remains unclear. The aim is to elucidate the mechanisms underlying resistance to antiviral therapy and predictive usefulness of gene quantification in chronic hepatitis C (CH-C). We conducted a human study in 74 CH-C patients treated with pegylated interferon alpha-2b and ribavirin and 5 nonviral control patients. Expression of viral sensors, adaptor molecule, related ubiquitin E3-ligase, and modulators were quantified. Hepatic RIG-I, MDA5, LGP2, ISG15, and USP18 in CH-C patients were up-regulated at 2- to 8-fold compared with nonhepatitis C virus patients with a relatively constitutive Cardif. Hepatic RIG-I, MDA5, and LGP2 were significantly up-regulated in nonvirologic responders (NVR) compared with transient (TR) or sustained virologic responders (SVR). Cardif and RNF125 were negatively correlated with RIG-I and significantly suppressed in NVR. Differences among clinical responses in RIG-I/Cardif and RIG-I/RNF125 ratios were conspicuous (NVR/TR/SVR = 1.3:0.6:0.4 and 2.3:1.3:0.8, respectively). Like viral sensors, ISG15 and USP18 were significantly up-regulated in NVR (4-fold and 2.3-fold, respectively). Multivariate and receiver operator characteristic analyses revealed higher RIG-I/Cardif ratio, ISG15, and USP18 predicted NVR. Lower Cardif in NVR was confirmed by its protein level in Western blot. Also, transcriptional responses in peripheral blood mononuclear cells to the therapy were rapid and strong except for Cardif in not only a positive (RIG-I, ISG15, and USP18) but also in a negative regulatory manner (RNF125). NVR may have adopted a different equilibrium in their innate immune response. High RIG-I/Cardif and RIG-I/RNF125 ratios and ISG15 and USP18 are useful in identifying NVR.Gastroenterology 06/2008; 134(5):1396-405. · 11.68 Impact Factor -
Article: The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy.
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ABSTRACT: Interferon (IFN) therapy leads to regression of hepatic fibrosis in chronic hepatitis C patients who achieve a sustained virologic response (SVR), while the beneficial effect is limited in those who fail to do so. The aim of the present study was to define factors associated with progression of fibrosis in patients who do not achieve a SVR. Fibrosis staging scores were compared between paired liver biopsies before and after IFN in 97 chronic hepatitis C patients who failed therapy. The mean interval between biopsies was 5.9 years. Factors associated with progression of fibrosis were analyzed. Fibrosis progressed in 23%, remained unchanged in 47% and regressed in 29%. Steatosis and a high average alanine aminotransferase (ALT) between biopsies were independent factors for progression of fibrosis with risk ratios of 5.53 and 4.48, respectively. Incidence and yearly rate of progression of fibrosis was 64% and 0.22+/-0.29 fibrosis units per year in those with both risk factors compared to 8% and -0.04+/-0.17 fibrosis units per year in those negative for both factors. Hepatic steatosis and elevated ALT levels are risk factors for progression of fibrosis in chronic hepatitis C patients who fail to achieve a SVR to IFN therapy and therefore may be therapeutic targets to halt the potentially progressive disease.Journal of Hepatology 06/2008; 48(5):736-42. · 9.26 Impact Factor -
Article: Targeting lipid metabolism in the treatment of hepatitis C virus infection.
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ABSTRACT: Recently, microdomains of organelle membranes rich in sphingomyelin and cholesterol (called "lipid rafts") have been considered to act as a scaffold for the hepatitis C virus (HCV) replication complex. Using the HCV cell culture system, we investigated the effect of myriocin, a sphingomyelin synthesis inhibitor, on HCV replication. We also investigated the combined effect of myriocin with interferon (IFN) and myriocin with simvastatin. Myriocin suppressed replication of both a genotype 1b subgenomic HCV replicon (Huh7/Rep-Feo) and genotype 2a infectious HCV (JFH-1 HCV) in a dose-dependent manner (for subgenomic HCV-1b, maximum of 79% at 1000 nmol/L; for genomic HCV-2a, maximum of 40% at 1000 nmol/L). Combination treatment with myriocin and IFN or myriocin and simvastatin attenuated HCV RNA replication synergistically in Huh7/Rep-Feo cells. Our data demonstrate that the sphingomyelin synthesis inhibitor strongly suppresses replication of both the subgenomic HCV-1b replicon and the JFH-1 strain of genotype 2a infectious HCV, indicating that lipid metabolism could be a novel target for HCV therapy.The Journal of Infectious Diseases 03/2008; 197(3):361-70. · 6.41 Impact Factor -
Article: Secretin-stimulating MRCP in patients with pancreatobiliary maljunction and occult pancreatobiliary reflux: direct demonstration of pancreatobiliary reflux.
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ABSTRACT: We propose the hypothesis that the enlargement of the common bile duct (CBD) or gallbladder (GB) that is occasionally demonstrated on magnetic resonance cholangiopancreatography (MRCP) after secretin stimulation is caused by pancreatobiliary reflux. Recently, occult pancreatobiliary reflux (OPR) has been demonstrated in patients without morphological pancreatobiliary maljunction (MPBM). The aim of this study was to evaluate the efficacy of secretin-stimulating MRCP (SMRCP) in the diagnosis of pancreatobiliary reflux. The study included 14 patients with MPBM and 32 patients with a normal pancreatobiliary junction. OPR was evaluated by bile collection and diagnosed in seven of the 32 patients. All the patients underwent SMRCP; the related findings were considered positive when enlargement of the CBD or GB was observed. Positive findings on SMRCP were observed in all MPBM patients. In the patients with normal pancreatobiliary junction, there was significant difference between the mean amylase levels in the patients with positive and negative SMRCP findings (mean, 4,755.7 and 29.7 IU/l). The sensitivity and specificity of SMRCP for diagnosing OPR was 85.7% and 68.0%, respectively. SMRCP provides a non invasive method for excluding PBR and can identify patients who could benefit from bile duct sampling to diagnose OPR.European Radiology 10/2007; 17(9):2262-7. · 3.22 Impact Factor -
Article: A Histopathological Study on Ventral and Dorsal Pancreas Tissues in Patients with Pancreas Divisum
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ABSTRACT: Five cases of pancreas divisum, clinically diagnosed by endoscopic retrograde choledochopancreatography (ERCP), were studied histopathologically. They consisted of four biopsied cases and one patient who underwent pancreatoduodenectomy under the diagnosis of a suspected pancreatic carcinoma. Fibrosis was found in three out of the five cases, two cases with fibrosis in the dorsal pancreas and one in the ventral pancreas. In the two dorsal fibrosis pancreas cases, fibrosis was distributed in the intra- and interlobular areas and was accompanied by atrophy or disappearance of the acinar cells. These findings were compatible with chronic obstructive pancreatitis, distal to a stricture of the pancreatic duct. In the one ventral fibrosis pancreas case, i. e., the pancreatoduodenectomized case, fibrosis was distributed mainly in the interlobular area associated with hemosiderin deposition. Hemosiderin deposition was also observed in inflammatory foci at the posterior aspect of the ventral pancreas. Hence, such interlobular fibrosis developed in relation to the inflammatory foci, and was not caused by pancreas divisum. Therefore, in pancreas divisum, abnormal findings were observed in the dorsal pancreas tissue, and they were compatible with chronic obstructive pancreatitis. (Dig Endosc 1994; 6 : 74–79)Digestive Endoscopy 08/2007; 6(1):74 - 79. · 1.19 Impact Factor
Top co-authors
Top Journals
Institutions
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2003–2011
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Musashino Red Cross Hospital
Tokyo, Tokyo-to, Japan
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2008
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Yamanashi University
- Faculty of Medicine
Kōfu-shi, Yamanashi-ken, Japan
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2003–2005
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Tokyo Medical and Dental University
- Department of Gastroenterology and Hepatology
Tokyo, Tokyo-to, Japan
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