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Yoshiaki Katano

Publications and source records attributed to Yoshiaki Katano.

17 recordsLinked to original sources
PubMed2007

A mutation in the interferon sensitivity-determining region is associated with responsiveness to interferon-ribavirin combination therapy in chronic hepatitis patients infected with a Japan-specific subtype of hepatitis C virus genotype 1B.

The interferon sensitivity-determining region (ISDR) is useful as a predictive marker of the response to interferon (IFN) therapy for chronic hepatitis patients with a Japan-specific subtype (J-type) of hepatitis C virus (HCV) genotype 1b. This marker is not useful for predicting responsiveness of a worldwide subtype (W-type) of HCV 1b, which could explain the restricted usefulness of this system only to Japan. In the present study, we examined the predictive value of the ISDR for ribavirin combination therapy. A total of 79 patients with HCV 1b comprising 35 patients with J-type and 44 patients with W-type were treated with IFN in combination with ribavirin for more than 48 weeks. Mutations in the ISDR were detected more frequently often seen in J-type HCV 1b than in W-type; however, the sustained virological response (SVR) rate for the combination therapy was similar between the two subtypes. Multivariate analysis revealed that factors associated with SVR were IFN dose and the number of amino acid substitutions in ISDR but not with subtypes J and W. The correlation between the number of substitutions in ISDR and responses to IFN-ribavirin combination therapy was restricted to patients with J-type HCV 1b. The ISDR is a useful predictive marker for response to IFN-ribavirin combination therapy in J-type HCV.

Drug Resistance, Viral↗
PubMed2006

Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: their correlation with response to interferon monotherapy and viral load.

AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2alpha phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9%, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

Adult↗
PubMed2006

Clofibrate treatment promotes branched-chain amino acid catabolism and decreases the phosphorylation state of mTOR, eIF4E-BP1, and S6K1 in rat liver.

Leucine stimulates protein synthesis by modulating the mammalian target of rapamycin (mTOR) signaling pathway. We hypothesized that promotion of the branched-chain amino acid (BCAA) catabolism might influence the leucine-induced protein synthesis. Clofibric acid (an active metabolite of clofibrate) is known to promote the BCAA catabolism by activation of branched-chain alpha-keto acid dehydrogenase complex (BCKDC), the rate-limiting enzyme of the BCAA catabolism. In the present study, we examined the phosphorylation state of mTOR, eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and ribosomal protein S6 kinase 1 (S6K1) in liver of rats with or without activation of the BCKDC by clofibrate treatment. Clofibrate-treated rats were prepared by oral administration of clofibrate 5 h before sacrifice. In order to stimulate phosphorylation of components in the mTOR signaling pathway, rats were orally administered with leucine 1 h before sacrifice. Clofibrate treatment almost fully activated hepatic BCKDC and significantly decreased the plasma leucine concentration in rats without leucine administration, resulting in decreased mTOR and 4E-BP1 phosphorylation. Similarly, in rats administered with leucine, clofibrate treatment attenuated the predicted increase in plasma leucine concentration as well as the phosphorylation of mTOR, 4E-BP1, and S6K1. These results suggest that BCAA catabolism enhanced by clofibrate treatment has significant influences on the leucine-induced activation of translation initiation processes.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2005

Changes in hepatitis C virus (HCV) antibody status in patients with chronic hepatitis C after eradication of HCV infection by interferon therapy.

BACKGROUND: Changes in hepatitis C virus (HCV) antibody status were followed for 10 years after the eradication of HCV by interferon (IFN) therapy in 30 patients with chronic hepatitis C who showed a sustained virological response. METHODS: HCV core antibody titer, third-generation HCV recombinant immunoblot assay (RIBA) grade (measuring the presence of antibodies for core, NS3, NS4, and NS5 antigens), and genotype-specific antibodies to the HCV NS4 region were measured annually with commercially available kits for these antibodies. RESULTS: For grade of HCV antibody determined by RIBA, the most significant decrease was observed with anti-NS5 antibody, followed by anti-NS4, anti-NS3, and anti-core antibodies, in that order. Tests for anti-NS5 and anti-NS4 antibodies had negative results in almost 50% of patients 10 years after eradication of HCV. In contrast, the results of tests for anti-core antibody were still markedly positive in most patients. However, anti-core antibody titer decreased continuously during the 10-year follow-up period. Antibodies to the NS4 region specific for HCV genotypes 1 and 2 also decreased during the follow-up period. Differences in the rate at which antibody titers decreased were observed between antibodies for genotypes 1 and 2; as a consequence, the serological type of HCV changed during the follow-up period in some patients. CONCLUSIONS: HCV antibody titer appears to continue to decrease during the 10 years after eradication of HCV by IFN therapy.

Adult↗
PubMed2005

Three patients with middle-age-onset hemochromatosis caused by novel mutations in the hemojuvelin gene.

Hemochromatosis is a genetically heterogeneous condition. Mutations in the recently described hemojuvelin gene were found in patients with juvenile hemochromatosis, who usually manifest clinical signs of iron overload, including cardiomyopathy and hypogonadism, in their teens and early 20s. In this report, we describe three Japanese patients who showed typical clinical and hepatic histological damage compatible with hemochromatosis at around 50 years of age. Genetic analyses showed that all three patients carried mutations in the hemojuvelin gene. The first patient was homozygous for a novel mutation (745G > C [D249H]), and the second and third patients from the same family were homozygous for another novel mutation (934C > T [Q312X]). No mutations in their HFE, hepcidin, transferrin receptor 2, or ferroportin genes were found. One patient had chronic infection with Helicobacter pylori. The age at initial presentation of hemojuvelin-hemochromatosis occurs over a wider range than previously described.

Age of Onset↗
PubMed2004

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan.

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.

Adult↗
PubMed2004

Mutations of the interferon sensitivity-determining region (ISDR) correlate with the complexity of hypervariable region (HVR)-1 in the Japanese variant of hepatitis C virus (HCV) type 1b.

Hepatitis C virus (HCV) genotype 1b comprises mainly two subtypes in Japan, each named for its geographic prevalence (Japan-specific, J type; worldwide, W type). Because the newly identified subtypes have not been fully characterized, the present study directed this issue from virological viewpoints such as hypervariable region (HVR)-1 as well as interferon (IFN) sensitivity-determining region (ISDR). Fifty chronic hepatitis patients with HCV 1b (31 men and 19 women; mean age 50.5 years) were enrolled, and J/W type was determined according to envelope 1 (E1) sequence as described previously (23 J type and 27 W type). Correlations between age, number of HVR-1 clones, HVR-1 diversity, and ISDR mutations were analyzed in J and W type patients independently. In addition, the sequences of the three HCV regions obtained for the determination of the above genetic factors were studied phylogenetically. The number of HVR-1 clones was significantly higher for J type in comparison with W type (P = 0.044). In the J type-infected patients, the ISDR mutation number was correlated inversely with HVR-1 clone number (P = 0.0001, r = -0.734) and HVR-1 diversity (P = 0.0001, r = -0.722). However, this correlation was not observed in the W type patients. W type patients showed a significant correlation between age and HVR-1 clone number (P = 0.015, r = 0.462). Phylogenetic study revealed that the nonstructural (NS) 5A sequence, which is obtained for ISDR type determination, can distinguish between J and W types. The inverse correlation in J type patients between ISDR mutations and HVR-1 complexity may explain the usefulness of the ISDR for prediction of IFN response only in Japanese patients. This suggests that the ISDR is not directly related to IFN responsiveness, but the degree of HVR-1 complexity may be more important.

Antiviral Agents↗
PubMed2004

The fluctuations of viral load and serum alanine aminotransferase levels in chronic hepatitis C.

Although viral load of hepatitis C virus (HCV) is a predictor of response to interferon therapy, little is known about its fluctuations. We assessed its fluctuations and their correlation with serum alanine aminotransferase (ALT) levels. Viral load was prospectively measured bimonthly for 22 months in 109 patients. In 40 patients, viral load changed more than five fold. Changes were transient and always returned to the baseline levels. ALT levels changed more than three fold in 30 patients. Changes of viral load accompanied simultaneous changes of ALT levels in only 7 of 40 patients with changes of viral load. Mean viral load in 22 months was significantly correlated with mean ALT levels inversely (r = 0.278, P = 0.0036). Mean viral load was significantly higher in 27 patients with persistently normal ALT levels (452.0 +/- 342.5pg/ml) than in 30 patients with changes of ALT levels (202.4 +/- 215.0pg/ml) (P = 0.0016) and than in 52 patients without changes of ALT levels (301.1 +/- 295.4pg/ml) (P = 0.0458). Inverse correlation of viral load with ALT levels suggests that viral load is in suppression by inflammatory activity. However, changes of ALT levels infrequently accompanied simultaneous changes of viral load and vice versa, as often seen in chronic hepatitis B virus infection.

Journal Article↗
PubMed2004

Effects of liver failure on branched-chain alpha-keto acid dehydrogenase complex in rat liver and muscle: comparison between acute and chronic liver failure.

BACKGROUND/AIMS: Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyses the committed step in the branched-chain amino acid (BCAA) catabolic pathway. In many cases of liver failure, the serum BCAAs/aromatic amino acids ratio (Fisher's ratio) decreases, and BCAAs have been administered to patients with liver failure to correct this ratio. We conducted an animal study to examine whether the effects on hepatic BCKDH complex differ between acute liver failure (ALF) and chronic liver failure (CLF). METHODS: ALF and CLF was induced in rats by a single high-dose injection and 21 weeks of repeated low-dose injections of carbon tetrachloride, respectively. Plasma BCAA and branched-chain alpha-keto acid (BCKA) levels, and activities and protein amounts of hepatic BCKDH complex and kinase were measured. RESULTS: ALF was characterized by elevated plasma BCAA and BCKA levels and decreased hepatic BCKDH activity. CLF was characterized by decreased plasma BCAA and BCKA levels and increased hepatic BCKDH activity. This increase in BCKDH activity in CLF was associated with the decreased BCKDH kinase, which is responsible for the BCKDH inactivation. CONCLUSIONS: The results obtained in the present study suggest that BCAA catabolism is suppressed in ALF and increased in CLF.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2003

Prevalence and characterization of hepatitis C virus genotype 4 in Japanese hepatitis C carriers.

Hepatitis C virus (HCV) can be classified into six major genotypes, the prevalences of which differ around the world. In Japan, the main genotypes are HCV 1 and HCV 2; others are found only rarely. Little is known about the prevalence in Japan of HCV genotype 4 which, is found frequently in North and Central Africa and the Middle East. Thus, we conducted a study to clarify distribution of HCV genotype 4 and the clinical demographics of patients with HCV genotype 4 in Japan. We examined HCV genotypes in 899 Japanese individuals with HCV viremia living in Aichi Prefecture, including 63 hemophiliacs. Four patients (0.4%) were infected with HCV genotype 4. All four of these patients were male hemophiliacs who had received clotting factors from foreign countries. Three patients were co-infected with human immunodeficiency virus (HIV); none were co-infected with GB virus-C/hepatitis G virus. Phylogenetic analysis of the El region indicated that all four patients were infected with subtype 4a. This subtype is related genetically to a subtype previously reported in Japanese and Italian hemophiliacs. HCV genotype 4 is indeed rare in Japan and may be detected only among hemophiliacs who have received inactivated clotting factor concentrates from foreign countries.

Journal Article↗
PubMed2003

Comparison of contrast-enhanced harmonic ultrasonography and power Doppler ultrasonography for depicting vascularity of hepatocellular carcinoma identified by angiography-assisted CT.

The sensitivity of contrast-enhanced harmonic gray scale imaging was compared with that of power Doppler sonography in depicting tumor vascularity and contrast enhancement of hepatocellular carcinoma (HCC) identified by angiography-assisted computed tomography (CT). One hundred thirty-nine classic HCC nodules (108 patients), each appearing as a high-attenuation mass on early-phase CT during hepatic arteriography and as a perfusion defect on CT during arterial portography, were evaluated. Vascular findings and contrast enhancement patterns were evaluated by contrast-enhanced harmonic gray scale imaging. Arterial pulsatile flow into each nodule was checked by power Doppler sonography. Sensitivity of each modality for depicting tumor vascularity was examined by angiography-assisted CT findings as the gold standard. The sensitivity of contrast-enhanced harmonic gray scale imaging (134/139, 96.4%) was significantly greater than that of power Doppler sonography (96/139, 69.1%) (P<0.05). Twenty-six of twenty-seven nodules (96.3%) in the lateral segment, in which motion artifact is likely, were enhanced by contrast-enhanced harmonic gray scale imaging. Contrast-enhanced harmonic gray scale imaging is more sensitive than power Doppler sonography and is a noninvasive method that can be used as effectively as angiography-assisted CT to evaluate tumor vessels and contrast enhancement of HCC.

Journal Article↗
PubMed2002

Evaluation of a new assay for hepatitis C virus genotyping and viral load determination in patients with chronic hepatitis C.

A new method for hepatitis C virus (HCV) genotyping that analyzes products generated with the HCV Amplicor Monitor Test has been developed. One hundred and sixty-two Japanese patients with chronic hepatitis C, including 59 patients with hemophilia, were tested for HCV genotypes and viral loads with this new test, and the results were compared with those of a genotyping assay that involved direct sequencing of the E1 region. HCV genotypes and viral loads were also compared between patients with and without hemophilia. There were no discrepancies between the two methods in determining genotypes 2a, 2b, and 3a. However, two patients infected with 1a were mistyped as 1b with the new assay. One patient not classified by this assay was genotype 4. Genotypes found in patients without hemophilia were 1b, 2a, and 2b. Genotypes 1a, 3a, and 4, which were minor variants in Japan, were detected only in patients with hemophilia. In addition, J type, which is a subtype of 1b that originated in Japan, was found at low frequency in hemophiliacs. Thus, the HCV genotypes in patients with hemophilia are likely to be of foreign origin. Overall, this new assay was accurate except for genotype 1a and 4, and allowed simultaneous assessment of genotype and viral load.

Adult↗
PubMedDate not supplied

Peripheral lymphocyte subsets vary with stage of hepatitis C virus-associated liver disease.

BACKGROUND/AIMS: Hepatitis C virus induces various clinical features in a host depending on duration of the viral infection. METHODOLOGY: We investigated peripheral lymphocyte subsets in patients with three different stages of hepatitis C virus infection: 5 patients with acute hepatitis, 10 with chronic hepatitis unassociated with cirrhosis, and 10 with cirrhosis. Peripheral lymphocytes were double-stained with multiple fluorescent antibody combinations: anti-CD3 plus anti-gammasigmaT cell receptor; anti-CD19 plus anti-CD5; anti-CD4 plus anti-CD45RA; or anti-CD8 plus anti-CD11b. Triple staining was performed with fluorescent antibodies against CD4, interferon gamma, and interleukin-4. Both staining protocols were followed by flow cytometric analysis. RESULTS: Acute hepatitis patients had a high proportion of CD3+ T cells with increased CD4+CD45RA-T helper and CD8+CD11b- cytotoxic T cells. Compared to this group, chronic hepatitis patients showed a decrease in CD4+ cells and an increase in CD19+ B cells and interleukin-4-producing Th2 cells. Cirrhotic patients showed decreased circulating lymphocytes and a low proportion of CD8+ cells accompanied by a decrease in cytotoxic T cells. Furthermore, their lymphocyte profiles showed decreases in primordial lymphocyte subpopulations (T cells with gammasigmaT cell receptors and B cells with CD5). CONCLUSIONS: Although the same pathogenic agent was involved, immune dynamics differed greatly according to duration of viral infection.

Acute Disease↗
PubMedDate not supplied

Clinical implications of measurement of serum nuclear matrix protein levels in patients with liver disease.

BACKGROUND/AIMS: Serum aminotransferase, a sensitive marker of hepatocellular damage, often poorly correlates with the severity of damage. Serum nuclear matrix protein (NMP), a structural protein released from dead cell nuclei, is investigated as a candidate marker of organ damage in liver disease. METHODOLOGY: Serum NMP and aminotransferase levels of 134 patients with various liver diseases and 26 healthy individuals were examined. RESULTS: Patients with chronic viral hepatitis showed slightly higher NMP levels (17.8 U/mL; 95% CI 15.0-20.5 U/mL) than those of healthy individuals (6.05 U/mL; 95% CI 4.82-7.27 U/mL). Their NMP values had no correlation with aminotransferase levels. NMP levels were similar irrespective of liver disease progression, whereas aminotransferase values decreased in parallel with progression. Patients with autoimmune hepatitis or primary biliary cirrhosis who were under an appropriate treatment as well as individuals with fatty liver showed no elevation of serum NMP levels. Patients with acute viral hepatitis showed very high NMP levels (38.8 U/mL; 95%CI 27.6-50.0 U/mL) that correlated with serum aminotransferase levels in their sera. CONCLUSIONS: In chronic liver diseases, the serum NMP level elevates to various degrees independent from the degree of aminotransferase elevation. Serum NMP, putatively representing the number of dead cells, is a candidate as an indicator of organ damage severity in liver disease.

Adult↗
PubMedDate not supplied

Recurrent hepatocellular carcinoma with rapid growth after cardiac surgery.

A 65-year-old man diagnosed with hepatitis C virus-positive hepatitis and severe valvular heart disease was scheduled to undergo cardiac valve replacement. We then found hepatocellular carcinoma in the liver. Because of his severe cardiac dysfunction, we treated him surgically with radiofrequency ablation for the hepatocellular carcinoma only. We continued medical treatment of the heart disease. He hoped to undergo with cardiac surgery one year later for the cardiac dysfunction. There was no evidence of tumor recurrence. We informed him that cardiac surgery requiring extracorporeal circulation might lead to tumor recurrence. He agreed to cardiac valve replacement, and the surgery was successful. Recurrent hepatocellular carcinoma was found in the liver 1 month after the surgery. Over the next month, the tumor progressed rapidly, showing portal vein thrombi. We believe the use of extracorporeal circulation in particular triggered the rapid growth of the recurrent hepatocellular carcinoma. This is the first report of a recurrent hepatocellular carcinoma associated with hepatitis C virus that progressed extensively after cardiac surgery.

Aged↗