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ABSTRACT: Background/Aims: The purpose of this retrospective study was to determine the characteristics of hepatocellular carcinoma (HCC) associated with lower, local recurrence rates after transcatheter arterial chemoembolization (TACE). Methodology: From 2005 to 2012, 93 consecutive patients with 125 nodules were included in this study. Patients were included if they had fewer than 3 hypervascular tumors, smaller than 4cm in diameter. Patients were excluded if they had a lack of iodized oil accumulation in target nodules on non-enhanced computed tomography (CT) immediately after TACE treatment. Mean lesion density in Hounsfield units (HU) was measured on non-enhanced CT imaging immediately after and 1 week after TACE. Results: The median lesion density on CT was 625HU (range 138-1911) immediately after and 431HU (range 89-2145) 1 week after TACE. Multivariate analysis using the Cox proportional hazard model revealed that an increase in lesion density (hazard ratio (HR), 0.18; p=0.002), des-gamma-carboxy prothrombin concentration (HR, 2.21; p=0.01), and lesion density on CT 1 week after TACE (HR, 0.46; p=0.02) were significant independent predictors associated with the lower, local recurrence rate after TACE treatment. Conclusions: In HCC without increased lesion density 1 week after TACE, it is possible to consider alternative or adjuvant treatments.
Hepato-gastroenterology 02/2013; 60(127). · 0.66 Impact Factor
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Takashi Honda,
Yoshiaki Katano, Teiji Kuzuya,
Kazuhiko Hayashi,
Masatoshi Ishigami,
Akihiro Itoh,
Yoshiki Hirooka,
Isao Nakano,
Tetsuya Ishikawa,
Hidenori Toyoda,
Takashi Kumada,
Koji Yamamoto,
Tadashi Matsushita,
Tetsuhito Kojima,
Junki Takamatsu,
Hidemi Goto
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ABSTRACT: Many patients with coagulation disorders are infected with hepatitis C virus (HCV) that advances to end stage liver disease, resulting in an increased number of deaths. The efficacy of ribavirin and peginterferon combination therapy for chronic HCV infection in patients with coagulation disorders has not been clarified fully. The aim of this study was to evaluate the efficacy and tolerability of combination therapy in this patient population compared with patients who are infected with HCV and do not have coagulation disorders. A total of 226 consecutive chronic hepatitis C patients were treated with combination therapy and divided into two groups: patients with (n = 23) and without coagulation disorders (n = 203). Clinical characteristics, sustained virological response rates obtained by an intention-to-treat analysis, and combination therapy discontinuation rates were compared between the two groups. The sustained virological response rates did not differ significantly between patients with and without coagulation disorders (65.2% vs. 47.8% by intention-to-treat analysis). According to a multivariate analysis, age, alanine aminotransferase, gamma-glutamyltransferase, and HCV genotype were associated significantly with a sustained virological response, whereas whether a patient had a coagulation disorder did not affect the sustained virological response. In conclusion, combination therapy for chronic hepatitis C was comparably effective between patients with and without coagulation disorders and did not result in adverse bleeding. J. Med. Virol. © 2012 Wiley Periodicals, Inc.
Journal of Medical Virology 11/2012; · 2.82 Impact Factor
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Kazuhiko Hayashi,
Yoshiaki Katano,
Hiroko Masuda,
Youji Ishizu, Teiji Kuzuya,
Takashi Honda,
Masatoshi Ishigami,
Akihiro Itoh,
Yoshiki Hirooka,
Isao Nakano,
Tetsuya Ishikawa,
Fumihiro Urano,
Kentaro Yoshioka,
Hidenori Toyoda,
Takashi Kumada,
Hidemi Goto
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ABSTRACT: AIM: Previous studies have suggested that patients with chronic hepatitis C with a low pretreatment hepatitis C virus (HCV) level have a high sustained virological response (SVR) rate, and that there would be a subpopulation of patients in which HCV can be eradicated with pegylated interferon (PEG IFN) alone without a decrease in SVR. However, the efficacy of PEG IFN monotherapy in patients with low HCV RNA levels is unclear. Several studies have reported that interferon sensitivity-determining region (ISDR) and the single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) contribute to IFN response, but these relationships are controversial. The aim of this study was to determine whether the SNP of IL-28B (rs8099917) and amino acid substitutions in the ISDR among patients with low HCV levels affect the response to PEG IFN monotherapy. METHODS: One hundred and four patients with low-level HCV infection were studied. Low HCV level was defined as 100 KIU/mL or less. RESULTS: SVR was achieved in 94 patients (92.2%). HCV levels (≤50 KIU/mL) and ISDR (≥2 mutations) were associated with SVR on univariate analysis. The rates of SVR in the patients with IL-28B genotypes TT, TG and GG were 94.5%, 77.8% and 100%, respectively. The G allele tended to be associated with poor response to IFN therapy (P = 0.0623). On multivariate analysis, the ISDR was the factor predictive of SVR (P = 0.004). CONCLUSION: The ISDR is significantly associated with a good response to PEG IFN monotherapy in patients with low HCV levels.
Hepatology Research 10/2012; · 2.20 Impact Factor
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ABSTRACT: Overproduction of hepatic very low-density lipoprotein (VLDL) particles is a major abnormality of lipoprotein dysregulation in type 2 diabetes (T2D). We sought to examine the relationship between systemic/hepatic inflammation associated with insulin resistance and apolipoprotein (apo)B100-containing VLDL production.
At the age of 19 wks, Otsuka Long-Evans Tokushima Fatty (OLETF) rats showed systemic inflammation (plasma TNF-α and interleukin (IL)-6 levels increased), insulin resistance (plasma retinol binding protein 4 and soluble CD36 levels were higher), dyslipidemia and fatty liver (plasma and liver triglyceride and cholesterol levels were higher as well as total VLDL-, VLDL(1)-, VLDL(2)-apoB100 and VLDL-triglycerides were overproduced), compared with the control rats. In livers of OLETF rats, mRNA levels of tnf, il1b and il6 were increased, but an anti-inflammatory protein, zinc finger protein 36, and its mRNA expression were decreased. We also found that the liver mRNA, protein levels, and tyrosine phosphorylation (pY) of insulin receptor (InsR) substrate (IRS) 2, but not IRS1, were decreased in OLETF rats; pY of InsR and Akt protein and phospho-Akt (ser437) were also reduced; but protein tyrosine phosphatase-1B protein was overexpressed. The gene expressions of glucose transporters 1 and 2, and glycogen synthase were decreased, but phosphatase and tensin homolog deleted on chromosome ten and glycogen synthase kinase 3β mRNAs were overexpressed, compared with the controls. Sterol regulatory element binding protein-1c mRNA, ATP-binding cassette transporter A1 mRNA, microsomal triglyceride transfer protein mRNA/protein, and CD36 mRNA/protein levels were increased and lipoprotein lipase and Niemann-Pick c1-like1 mRNA levels were decreased, which are all involved in lipogenesis. Decreased sirtuins1-3 mRNA levels were also observed in OLETF rats.
These abnormal genes, proteins expression and phosphorylation of multiple pathways related to inflammatory, insulin signaling and lipogenesis may be important underlying factors in VLDL-apoB100 particles overproduction observed in T2D. Our data contribute to the further understanding of an association of dyslipoproteinemia with systemic metabolic disorders, fatty liver and dysregulated hepatic metabolic pathways.
Atherosclerosis 04/2012; 222(2):409-16. · 3.79 Impact Factor
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Kazuhiko Hayashi,
Yoshiaki Katano, Teiji Kuzuya,
Yoshihiko Tachi,
Takashi Honda,
Masatoshi Ishigami,
Akihiro Itoh,
Yoshiki Hirooka,
Tetsuya Ishikawa,
Isao Nakano,
Fumihiro Urano,
Kentaro Yoshioka,
Hidenori Toyoda,
Takashi Kumada,
Hidemi Goto
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ABSTRACT: Hepatitis C virus (HCV) genotype 1a is rare in Japanese patients and the clinical characteristics of this genotype remain unclear. The interferon (IFN) sensitivity-determining region (ISDR) and single-nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) among patients with HCV genotype 1b are associated with IFN response, but associations among patients with genotype 1a are largely unknown. This study investigated the clinical characteristics of genotype 1a and examined whether genomic heterogeneity of the ISDR and SNPs of IL28B among patients with HCV genotype 1a affects response to combination therapy with pegylated-IFN-α2b and ribavirin. Subjects comprised 977 patients infected with HCV genotype 1, including 574 men and 412 women (mean age, 55.2 ± 10.6 years). HCV was genotyped by direct sequencing of the 5'-untranslated region and/or core regions and confirmed by direct sequencing of the NS5A region. HCV genotypes 1a (n = 32) and 1b (n = 945) were detected. Twenty-three (71.9%) of the 32 patients with genotype 1a were patients with hemophilia who had received imported clotting factors. Prevalence of genotype 1a after excluding patients with hemophilia was thus 0.9%. Of the 23 patients with genotype 1a who completed IFN therapy, 11 (47.8%) were defined as achieving sustained virological response. Factors related to sustained virological response by univariate analysis were IL28B and ISDR. In conclusion, HCV genotype 1a is rare in Japan. The presence of IL28B genotype TT, and more than two mutations, in the ISDR are associated with a good response to IFN therapy in patients with HCV genotype 1a.
Journal of Medical Virology 03/2012; 84(3):438-44. · 2.82 Impact Factor
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Teiji Kuzuya,
Yasuhiro Asahina,
Kaoru Tsuchiya,
Keisuke Tanaka,
Yuichiro Suzuki,
Takahide Hoshioka,
Shinji Tamaki,
Tomoji Kato,
Yutaka Yasui,
Takahiro Hosokawa,
Ken Ueda,
Hiroyuki Nakanishi,
Jun Itakura,
Yuka Takahashi,
Masayuki Kurosaki,
Namiki Izumi
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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
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ABSTRACT: We report a case of an 80-year-old male who suffered from intractable hepatic encephalopathy and hepatocellular carcinoma( HCC), associated with hepatitis type C-related liver cirrhosis. He was unable to receive HCC treatment due to the deterioration of his liver. His hepatic encephalopathy was resistant to oral administration of laxatives, lactulose, and kanamycin sulfate, etc. His blood ammonia concentration averaged about 130 mg/dL, and often exceeded 200 mg/dL(normal range: <80 mg/dL). Later, an oral administration of vancomycin hydrochloride, 0. 5 g once every 3 days, was initiated. Soon after ward, his blood ammonia concentration declined to the normal range(about 50 mg/dL), and the clinical symptoms of hepatic encephalopathy showed a remarkable improvement. By the continuation of vancomycin administration, the normalization of his state of consciousness was achieved, improving his quality of life, and his activities of daily living. Three months after beginning treatment, he was able to receive transcatheter arterial chemoembolization for the treatment of HCC, because his liver function reserve improved(Child-Pugh score decreased from 10 to 7).
Gan to kagaku ryoho. Cancer & chemotherapy 06/2011; 38(6):995-7.
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Jun Itakura,
Yasuhiro Asahina,
Nobuharu Tamaki,
Itsuko Hirayama,
Yutaka Yasui,
Tomohiro Tanaka,
Mitsuaki Sato,
Ken Ueda, Teiji Kuzuya,
Kaoru Tsuchiya,
Hiroyuki Nakanishi,
Masayuki Kurosaki,
Gretchen S. Gabriel,
George J. Schneider,
Namiki Izumi
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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
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Masayuki Kurosaki,
Yasuhito Tanaka,
Keisuke Tanaka,
Yuichiro Suzuki,
Yoshihide Hoshioka,
Nobuharu Tamaki,
Tomoji Kato,
Yutaka Yasui,
Takanori Hosokawa,
Ken Ueda, [......],
Jun Itakura,
Yuka Takahashi,
Yasuhiro Asahina,
Kentaro Matsuura,
Fuminaka Sugauchi,
Nobuyuki Enomoto,
Nao Nishida,
Katsushi Tokunaga,
Masashi Mizokami,
Namiki Izumi
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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
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Kaoru Tsuchiya,
Mina Komuta,
Yutaka Yasui,
Nobuharu Tamaki,
Takanori Hosokawa,
Ken Ueda, Teiji Kuzuya,
Jun Itakura,
Hiroyuki Nakanishi,
Yuka Takahashi,
Masayuki Kurosaki,
Yasuhiro Asahina,
Nobuyuki Enomoto,
Michiie Sakamoto,
Namiki Izumi
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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
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Gan to kagaku ryoho. Cancer & chemotherapy 10/2010; 37(10):1883-86.
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Masayuki Kurosaki,
Takanori Hosokawa,
Kotaro Matsunaga,
Itsuko Hirayama,
Tomohiro Tanaka,
Mitsuaki Sato,
Yutaka Yasui,
Nobuharu Tamaki,
Ken Ueda,
Kaoru Tsuchiya, Teiji Kuzuya,
Hiroyuki Nakanishi,
June Itakura,
Yuka Takahashi,
Yasuhiro Asahina,
Nobuyuki Enomoto,
Namiki Izumi
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ABSTRACT: Aim: Hepatic steatosis is linked to development of hepatocellular carcinoma (HCC) in non-viral liver disease such as non-alcoholic steatohepatitis. The present study aimed to assess whether hepatic steatosis is associated with the development of HCC in chronic hepatitis C.Methods: We studied a retrospective cohort of 1279 patients with chronic hepatitis C who received interferon (IFN) therapy between 1994 and 2005 at a single regional hospital in Japan. Of these patients, 393 had a sustained virological response (SVR) and 886 had non-SVR to IFN therapy. After IFN therapy, these patients were screened for development of HCC every 6 months. The average period of observation was 4.5 years.Results: HCC developed in 68 patients. The annual incidence of HCC was 2.73% for patients with a steatosis grade of 10% or greater and 0.69% for patients with a steatosis grade of 0–9%. On multivariate analysis, higher grade of steatosis was a significant risk factor for HCC independent of older age, male sex, higher body mass index (BMI), advanced fibrosis stage and non-SVR to IFN therapy. The adjusted risk ratio of hepatic steatosis was 3.04 (confidence interval 1.82–5.06, P < 0.0001), which was higher than that of older age (1.09), male sex (2.12), non-SVR to IFN (2.43) and higher BMI (1.69).Conclusion: Hepatic steatosis is a significant risk factor for development of HCC in chronic hepatitis C independent of other known risk factors, which suggest the possibility that amelioration of hepatic steatosis may prevent hepatocarcinogenesis.
Hepatology Research 08/2010; 40(9):870 - 877. · 2.20 Impact Factor
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Yasuhiro Asahina,
Kaoru Tsuchiya,
Nobuharu Tamaki,
Itsuko Hirayama,
Tomohiro Tanaka,
Mitsuaki Sato,
Yutaka Yasui,
Takanori Hosokawa,
Ken Ueda, Teiji Kuzuya,
Hiroyuki Nakanishi,
Jun Itakura,
Yuka Takahashi,
Masayuki Kurosaki,
Nobuyuki Enomoto,
Namiki Izumi
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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
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Teiji Kuzuya,
Kinichi Takeda,
Setsuo Utsunomiya,
Masahiro Taga,
Noboru Kawata,
Takashi Ikeda,
Norihiro Imai,
Yoshitaka Mizutani,
Ken Hirose,
Tetsuya Ishikawa,
Yoshiaki Katano,
Hidemi Goto
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ABSTRACT: The patient was a 59-year-old male with chronic hepatitis type B. He was diagnosed as having multiple hepatocellular carcinomas (HCCs), most of which showed hypervascular features on contrast-enhanced CT scan. He underwent the implantation of a 5-french catheter by" GDA coil method" for hepatic arterial infusion of chemotherapy. After the implantation, he suffered from high fever with a sharp elevation in transaminase levels. Since his liver function gradually deteriorated, he was not able to receive hepatic arterial infusion of chemotherapy. However, three weeks after catheter implantation, most of the tumors were no longer enhanced on dynamic CT scan, suggesting a loss of tumor vascularity, ie, induction of tumor necrosis. It was speculated that necrosis of the tumors was caused by the reduction of hepatic arterial blood flow due to the catheter placement.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2377-9.
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ABSTRACT: Colonic perforation is a rare but life-threatening complication of colonoscopy. We evaluated the incidence of colonic perforation that resulted from colonoscopy in patients who underwent hemodialysis compared with those who did not have this procedure (controls).
Data from a total of 15,098 consecutive patients who underwent colonoscopy from January 2001 to December 2008 in Nagoya Kyoritsu Hospital were analyzed retrospectively. Patients were divided into 2 groups: 1106 hemodialysis patients and 13,992 controls. The incidence of colonic perforation, patient characteristics, and locations of perforation during colonoscopy were compared between the 2 groups. Furthermore, perforated mucosa samples from colons were examined by pathology analysis.
Colonic perforations occurred in 5 hemodialysis patients and 3 controls. The incidence of colonic perforation was markedly higher in the hemodialysis group than in the control group (0.45% vs 0.02%; odds ratio, 21.17; 95% confidence interval, 5.05-88.73; P < .0001). Even after multivariate analysis of age, sex, and patients who received polypectomies, hemodialysis still was associated independently with the risk of colonic perforation during colonoscopy (odds ratio, 19.91; 95% confidence interval, 4.61-85.93; P < .0001). Pathologic examination of perforated mucosa was performed in 3 hemodialysis patients and 3 control patients. beta2-microglobulin deposition was observed in all 3 hemodialysis patients. In contrast, beta2-microglobulin deposition was not detected in control patients.
There is a higher risk of colonic perforation during colonoscopy among patients who received hemodialysis compared with those who did not. beta2-microglobulin deposition might have a role in perforation in patients who receive hemodialysis.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2009; 8(1):55-9. · 5.64 Impact Factor
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Tomohiko Ohashi,
Junichi Tanabe,
Tetsuya Ishikawa,
Akihiko Okumura,
Ken Sato,
Minoru Ayada,
Naoki Hotta, Teiji Kuzuya,
Hiroyasu Ito,
Haruhisa Nakao,
Masashi Yoneda,
Shinichi Kakumu
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ABSTRACT: Aim: Human hepatocytes are known to express an array of inflammatory cytokines and chemokines. In this study, we examined the potential roles of hepatocytes in regulating immune responses in the liver, by assessing the induction of Th1- or Th2-specific chemokines in HepG2 cells after various inflammatory stimulations. Methods: HepG2 cells were stimulated with IL-1alpha, IFN-gamma, IL-4, IL-10, and/or CCL2, harvested at several time points, and served for the analyses of cytokine/chemokine mRNA expressions by semi-quantitative RT-PCR. Results: (i) IL-1alpha up-regulated mRNA levels of CXCL8, CXCL10, and CCL2. IFN-gamma increased those of CXCL9, CXCL10, and CCL5, while IL-4 or IL-10 had no effect. (ii) Addition of IL-4 to the culture of IFN-gamma-stimulated cells, down-regulated CXCL9 and CXCL10 mRNA levels. (iii) Addition of IFN-gamma to the culture of IL-1alpha-stimulated cells, further up-regulated CXCL9 and CXCL10 mRNA levels. Addition of IL-4 decreased CXCL8 and CXCL10 levels, and increased CCL2 level in IL-1alpha-stimulated cells. (iv) CCL2 induced IL-4 mRNA expression. Conclusions: IFN-gamma augmented mRNA expression of Th1-specific chemokines (CXCL9 and CXCL10) in HepG2 cells. IL-4 had no effect on those of Th2-spesific chemokines (CCL17 and CCL22); however, it was supposed to augment Th2 response indirectly through the induction of CCL2 under the inflammatory condition. The findings suggest that hepatocytes have ability to promote immune responses in the liver toward the direction, initially determined by the cytokine balances in the local inflammatory region.
Hepatology Research 03/2009; 39(5):510-9. · 2.20 Impact Factor
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Teiji Kuzuya,
Yoshiaki Katano,
Isao Nakano,
Yoshiki Hirooka,
Akihiro Itoh,
Masatoshi Ishigami,
Kazuhiko Hayashi,
Takashi Honda,
Hidemi Goto,
Yuko Fujita,
Rie Shikano,
Yuji Muramatsu,
Gustavo Bajotto,
Tomohiro Tamura,
Noriko Tamura,
Yoshiharu Shimomura
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ABSTRACT: The branched-chain alpha-keto acid dehydrogenase (BCKDH) complex is the most important regulatory enzyme in branched-chain amino acid (BCAA) catabolism. We examined the regulation of hepatic BCKDH complex activity in spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Zucker diabetic fatty rats. Hepatic BCKDH complex activity in these rats was significantly lower than in corresponding control rats. The amount of BCKDH complex in OLETF rats corresponded to the total activity of the complex. Activity and abundance of the bound form of BCKDH kinase, which is responsible for inactivation of the complex, showed an inverse correlation to BCKDH complex activity in OLETF rats. Dietary supplementation of 5% BCAAs for 10 weeks markedly increased BCKDH complex activity, and decreased the activity and bound form of BCKDH kinase in the rats. These results suggest that BCAA catabolism in type 2 diabetes is downregulated and enhanced by BCAA supplementation.
Biochemical and Biophysical Research Communications 09/2008; 373(1):94-8. · 2.48 Impact Factor
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Teiji Kuzuya,
Yoshiaki Katano,
Takashi Kumada,
Hidenori Toyoda,
Isao Nakano,
Yoshiki Hirooka,
Akihiro Itoh,
Masatoshi Ishigami,
Kazuhiko Hayashi,
Takashi Honda,
Hidemi Goto
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ABSTRACT: The aim of this study was to determine whether antiviral therapy with lamivudine is beneficial in patients after initial treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
Forty-nine consecutive patients with HBV-related HCC completely treated by hepatic resection or radiofrequency ablation were retrospectively enrolled in this study. Comparison was made between 16 patients who received lamivudine therapy at a dose of 100 mg/day after treatment for HCC (lamivudine group) and 33 patients who did not (control group) in terms of changes in remnant liver function, HCC recurrence and survival.
Cumulative recurrence rates of HCC did not significantly differ between the two groups (P = 0.622). However, median Child-Pugh score at the time of HCC recurrence was significantly different; 5 (range 5-6) in the lamivudine group versus 7 (range 5-12) in the control group (P = 0.005). All patients in the lamivudine group were able to receive curative treatment for recurrent HCC. In contrast, 10 of 15 patients in the control group were unable to receive curative optimal therapy for recurrent HCC due to deterioration of remnant liver function. The cumulative survival rates of patients in the lamivudine group tended to be higher than those of patients in the control group (P = 0.063).
It is suggested that lamivudine therapy is beneficial for patients after initial treatment for HBV-related HCC because it contributes to improving remnant liver function, thus decreasing the risk of liver failure and increasing the chances of receiving available treatment modalities for recurrent HCC.
Journal of Gastroenterology and Hepatology 12/2007; 22(11):1929-35. · 2.87 Impact Factor
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Teiji Kuzuya,
Takashi Kumada,
Seiki Kiriyama,
Yasuhiro Sone,
Makoto Tanikawa,
Yasuhiro Hisanaga,
Hidenori Toyoda,
Kazuhiko Hayashi,
Koji Nonogaki,
Junichi Shimizu,
Naoto Kawase,
Takahiro Yamauchi,
Toshiaki Kawachi,
Hideo Ichikawa
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 09/2006; 25(8):1099-103. · 1.25 Impact Factor
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ABSTRACT: We treated 665 patients with chronic hepatitis C with interferon (IFN) monotherapy and 288 with combined IFN and ribavirin. At the baseline, age (53.8 +/- 11.1 vs. 49.7 +/- 10.5 years, p < 0.0001) and activity (p = 0.0207) as well as fibrosis (p = 0.0270) were higher in patients who received combination therapy than in those receiving monotherapy. Compliance to treatment (64.2 vs. 62.1%, p < 0.0001) and discontinuation were more frequent (18.1 vs. 14.5%, p < 0.0001) in patients with combination therapy than in those with monotherapy. Patients with combination therapy with genotype 2 infection achieved sustained viral response (SVR) at a rate of 77.0%, regardless of viral loads, in contrast to those with genotype 1 infection, of whom only 24.4% gained SVR. Of patients with combination therapy, reduction (42.6 vs. 29.0%, p = 0.0453) and discontinuation (34.0 vs. 21.6%, p = 0.0414) of ribavirin were more frequently required in the 47 patients > or =65 years than in the 241 patients <65 years. Although a trend for higher SVR to combination therapy was observed in patients aged < 65 than in those aged > or =65 years (39.4 vs. 25.2%), the difference was not significant (p = 0.0819). In patients with genotype 1 infection, IFN monotherapy in addition to the 24-week combination therapy increased the SVR rate (18.3 vs. 42.6%, p = 0.0003). A decrease in SVR was observed with an increased body mass index in patients who received combination therapy.
Intervirology 01/2006; 49(1-2):112-8. · 2.34 Impact Factor
