85 results on '"Morihara D"'
Search Results
2. The Male Of Baetis macdunnoughi New record And Notes On Parthenogenetic Populations Within Baetis Ephemeroptera Baetidae
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Mccafferty, W P, Morihara, D K, and BioStor
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- 1979
3. The Baetis Larvae of North America (Ephemeroptera:Baetidae)
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Morihara, D. K. and McCafferty, W. P.
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- 1979
4. Development of high resolution and high shockproof MEMS accelerometer for monitoring of structures
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Morihara, D., primary, Tatara, Y., additional, Nakagawa, Y., additional, Hosoya, K., additional, and Seki, T., additional
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- 2015
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5. P0152 : The effect of irsogladine maleate for Portal Hypertensive Gastropathy (PHG)
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Yokoyama, K., primary, Irie, M., additional, Anan, A., additional, Fukuda, S., additional, Thuchiya, N., additional, Fukunaga, A., additional, Takata, K., additional, Tanaka, T., additional, Hanano, T., additional, Hirano, G., additional, Morihara, D., additional, Takeyama, Y., additional, Shakado, S., additional, Sohda, T., additional, and Sakisaka, S., additional
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- 2015
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6. Levels of the Oxidative Stress Marker γ-Glutamyltranspeptidase at Different Stages of Nonalcoholic Fatty Liver Disease
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Irie, M, primary, Sohda, T, additional, Iwata, K, additional, Kunimoto, H, additional, Fukunaga, A, additional, Kuno, S, additional, Yotsumoto, K, additional, Sakurai, K, additional, Iwashita, H, additional, Hirano, G, additional, Ueda, Si, additional, Yokoyama, K, additional, Morihara, D, additional, Nishizawa, S, additional, Anan, A, additional, Takeyama, Y, additional, Sakamoto, M, additional, Shakado, S, additional, and Sakisaka, S, additional
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- 2012
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7. 1006 WHY IS RADIOFREQUENCY ABLATION THERAPY (RFA) APPLIED FOR HEPATOCELLULAR CARCINOMA (HCC) UP TO 3 NODULES AND SMALLER THAN 3 CM IN TUMOR SIZE?
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Hirano, G., primary, Yokoyama, K., additional, Morihara, D., additional, Takeyama, Y., additional, Sakamoto, M., additional, Irie, M., additional, Iwata, K., additional, Shakado, S., additional, Sohda, T., additional, and Sakisaka, S., additional
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- 2012
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8. Characteristic Genotypes of Vascular Endothelial Growth Factor are Susceptible to Ascites in Patients with Cirrhosis
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Sohda, T, primary, Iwata, K, additional, Irie, M, additional, Takeyama, Y, additional, Nakane, H, additional, Morihara, D, additional, Kitamura, Y, additional, Yokoyama, M, additional, Shakado, S, additional, Watanabe, H, additional, and Sakisaka, S, additional
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- 2009
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9. Novel fabrication of micro-nano mixed 3D-structure by advanced hybrid nanoimprint lithography
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Okuda, K., primary, Morihara, D., additional, Kawata, H., additional, and Hirai, Y., additional
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- 2007
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10. The evolution of Heterocloeon with the first larval description of Heterocloeon frivolus comb. n. (Ephemeroptera: Baetidae).
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Morihara, D. K. and McCafferty, W. P.
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- 1979
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11. Notobaetis: A New Genus of Baetidae (Ephemeroptera) from South America.
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Morihara, D. K. and Edmunds, George F.
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- 1980
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12. The Family Teneriffiidae Thor, with a New Species from Mexico1
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McDaniel, B., primary, Morihara, D., additional, and Lewis, J. K., additional
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- 1976
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13. Systematics of the propinquus Group of Baetis Species (Ephemeroptera: Baetidae) 1
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Morihara, D. K., primary and McCafferty, W. P., additional
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- 1979
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14. Notobaetis: A New Genus of Baetidae (Ephemeroptera) from South America
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Morihara, D. K., primary and Edmunds, George F., additional
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- 1980
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15. The evolution ofHeterocloeonwith the first larval description ofHeterocloeon frivoluscomb. n. (Ephemeroptera: Baetidae)
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Morihara, D. K., primary and McCafferty, W. P., additional
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- 1979
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16. Branched Chain Amino Acids May Improve Liver Function.
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Morihara, D. and Iwata, K.
- Abstract
In a study involving 30 patients with liver cirrhosis who had undergone radiofrequency ablation for hepatocellular carcinoma, consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late evening snack was found to be associated with rapid and significant improvements in albumin and total serum bilirubin levels and in Child-Pugh scores at 4 and 12 weeks post-radiofrequency ablation. These benefits were not found in subjects fed a BCAA-enriched nutrient mixture in the morning. The authors conclude, "Late evening snack with BCAA supplementation significantly and rapidly improves liver functioning and CPS in liver cirrhosis patients who have undergone radiofrequency ablation for hepatocellular carcinoma." In addition they found that "Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance." [ABSTRACT FROM AUTHOR]
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- 2012
17. Malnutrition and inflammation status in nonobese patients with inflammatory bowel disease are associated with nonalcoholic fatty liver disease: a retrospective study.
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Nagata T, Funakoshi S, Morihara D, Shakado S, Yokoyama K, Takata K, Tanaka T, Fukunaga A, Yamauchi R, Fukuda H, Matsuoka H, Imakiire S, Sakisaka H, Matsuoka S, Kuno N, Abe K, Ishibashi H, Ashizuka S, and Hirai F
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Background/aims: The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify characteristics of NAFLD in patients with IBD., Methods: We retrospectively identified and enrolled patients with IBD diagnosed with or without NAFLD by undergoing abdominal computed tomography (CT) at our institution between 2005 and 2020. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of nonobese patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters., Results: Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In nonobese patients (defined as patients with a body mass index <25 kg/m2), C-reactive protein (CRP; P<0.001) and alanine aminotransferase (P=0.018) levels were higher and the albumin level (P=0.005) and prognostic nutritional index (PNI; P=0.002) values were lower in patients with NAFLD than in those without NAFLD. The PNI value was positively correlated (P<0.001) and the CRP level was negatively correlated (P=0.001) with the hepatosplenic ratio. However, in the NAFLD combined group, PNI (P<0.05) and CRP values (P<0.001) were improved over time after CT imaging by continuing IBD treatment., Conclusions: Worsening nutritional and inflammatory status in IBD patients is associated with complications of NAFLD. Diagnosis of NAFLD in IBD patients using CT imaging might be useful not only for early detection of NAFLD but also in assessing the need for therapeutic intervention for IBD.
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- 2023
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18. Nicotinic cholinergic regulation of olfactory bulb blood flow response in aged rats.
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Uchida S, Moriya J, Morihara D, and Kagitani F
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- Animals, Rats, Olfactory Bulb, Amides, Cholinergic Agents, Nicotine pharmacology, Receptors, Nicotinic
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In our previous research, we had demonstrated the crucial role of neuronal nicotinic acetylcholine receptors (nAChRs) in potentiation of the olfactory bulb blood flow response to olfactory stimulation in adult rats. The present study examined the effects of nAChR activation on the olfactory bulb blood flow response in rats aged 24-27 months. We found that, under urethane anesthesia, unilateral olfactory nerve stimulation (300 μA, 20 Hz, 5 s) increased blood flow within the ipsilateral olfactory bulb, without changes in the systemic arterial pressure. The increase in blood flow was dependent upon the current and frequency of the stimulus. Intravenous administration of nicotine (30 μg/kg) had little effect on the olfactory bulb blood flow response to nerve stimulation at either 2 Hz or 20 Hz. These results suggest a reduction in nAChR-mediated potentiation of the olfactory bulb blood flow response in aged rats., (© 2023. The Author(s).)
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- 2023
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19. Multiple focal fatty changes in the liver in patients with porphyria cutanea tarda: A case series and review of the literature.
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Takata K, Fukunaga A, Nishizawa S, Uchida Y, Fukuyama M, Nagata T, Higashi T, Fukuda H, Yamauchi R, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Humans, Ultrasonography adverse effects, Porphyria Cutanea Tarda complications, Porphyria Cutanea Tarda diagnostic imaging
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Porphyria cutanea tarda (PCT) is commonly diagnosed in cases where multiple hyperechoic nodules are observed in the liver. Pathologically, these nodules associated with PCT are focal fatty deposits. We report here, seven cases of PCT with fatty changes over multiple foci in the liver. Furthermore, the characteristics of ultrasonography (US) findings of 32 previously reported cases are summarized. The US features of these nodules showed a homogenous hyperechoic or hyperechoic rim pattern, partial confluence, and no mass effect in the vascular structures. Because multiple hyperechoic liver nodules occasionally mimic malignancies, and because their diagnosis can be challenging, clinicians should consider checking urine porphyrin levels to rule out PCT when such nodules are observed on US., (© 2021 Wiley Periodicals LLC.)
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- 2022
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20. Male-specific Association between Iron and Lipid Metabolism Changes and Erythroferrone after Hepatitis C Virus Eradication.
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Inomata S, Morihara D, Anan A, Yamauchi E, Yamauchi R, Takata K, Tanaka T, Yokoyama K, Takeyama Y, Irie M, Shakado S, Sohda T, Sakisaka S, and Hirai F
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- Antiviral Agents therapeutic use, Female, Genotype, Hepacivirus genetics, Humans, Iron, Lipid Metabolism, Male, Retrospective Studies, Hepatitis C complications, Hepatitis C drug therapy, Hepatitis C, Chronic complications
- Abstract
Objective Hepatitis C virus (HCV) eradication is associated with decreased serum ferritin and increased serum low-density lipoprotein-cholesterol (LDL-C) levels, although the mechanisms underlying these changes remain unclear. This study aimed to identify the mechanisms underlying the changes in iron and lipid metabolism after HCV eradication. Methods We retrospectively investigated iron and lipid metabolism changes in 22 patients with chronic hepatitis or compensated liver cirrhosis with HCV genotype 1b infection after HCV eradication. We measured the serum erythroferrone (ERFE) levels to assess the association with these metabolic changes. Patients were administered ledipasvir 90 mg and sofosbuvir 400 mg once daily for 12 weeks and were observed for 12 more weeks to evaluate the sustained virological response. Results Half of the patients were men. At baseline, the serum ferritin and ERFE levels were elevated, while the serum LDL-C levels were within the normal range. All patients achieved a sustained virological response at 24 weeks; furthermore, the serum ferritin and ERFE levels were significantly decreased, and the serum LDL-C levels were significantly increased at 24 weeks from baseline (p<0.001, all). In men, a decrease in serum ERFE levels was correlated with changes in the serum ferritin and LDL-C levels (r=0.78, p<0.01; r=-0.76, p<0.01, respectively). In addition, a decrease in the serum ferritin levels was correlated with an increase in the serum LDL-C levels (r=-0.89, p<0.001). These correlations were not observed in women. Conclusion Our results suggest a possible association between iron and lipid metabolism changes and the involvement of ERFE after HCV eradication in men as well as potential sex-related differences.
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- 2022
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21. Suppression of Local Tumor Progression in Perivascular Hepatocellular Carcinoma by Combination Therapy with Radiofrequency Ablation and Percutaneous Ethanol Injection: A Propensity Score Matching Analysis.
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Takata K, Tanaka T, Anan A, Fukunaga A, Nagata T, Fukuda H, Yamauchi R, Kunimoto H, Yokoyama K, Morihara D, Takeyama Y, Iwata K, Shakado S, Sakisaka S, and Hirai F
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- Ethanol, Humans, Propensity Score, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Catheter Ablation, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Radiofrequency Ablation
- Abstract
Background and Aims: Radiofrequency ablation (RFA) has replaced percutaneous ethanol injection (PEI) as the treatment of choice for hepatocellular carcinoma (HCC); however, control of local tumor progression (LTP) remains a challenge in perivascular HCC. The aim of this study was to determine whether PEI added to RFA can reduce the LTP rate in perivascular HCC patients., Methods: We retrospectively analyzed 167 patients, with 197 newly diagnosed HCC nodules with peritumoral vessels, who underwent either RFA plus PEI or RFA monotherapy as the first-line treatment between June 2001 and April 2015. Ethanol was injected inside the tumor close to the peritumoral vessels in the combination therapy group. Patients were matched 1:1 according to their propensity scores to reduce selection bias; cumulative LTP was then analyzed using log-rank tests and Cox proportional hazard regression analyses., Results: The two matched groups comprised 62 tumors each. The overall median follow-up period was 34 months (range, 1-140 months). In the RFA plus PEI group, the cumulative LTP rates were 5.7%, 15.5%, and 20.4% at 1, 3, and 5 years, respectively; in the RFA monotherapy group, the rates were 13.2%, 32.0%, and 40.2%, respectively. The rates were significantly lower in the RFA plus PEI group (p = 0.032). Cox proportional hazard regression analysis showed that PEI combination treatment was significantly associated with a reduced risk of local HCC recurrence (hazard ratio, 0.44; 95% confidence interval, 0.19-0.93; p = 0.031)., Discussion/conclusion: The risk of LTP after RFA for perivascular HCC can be significantly reduced by injecting ethanol close to the peritumoral vessels., (© 2022 S. Karger AG, Basel.)
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- 2022
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22. Gastroesophageal Varices and Hyperplastic Nodules of the Liver in a Patient with Anorexia Nervosa.
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Takata K, Nagata T, Uchida Y, Kitaguchi T, Higashi T, Fukuda H, Yamauchi R, Tsuchiya N, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Hamada Y, Yoshimitsu K, Sakisaka S, and Hirai F
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- Adult, Female, Humans, Liver diagnostic imaging, Anorexia Nervosa complications, Anorexia Nervosa diagnosis, Esophageal and Gastric Varices diagnosis, Esophageal and Gastric Varices etiology, Hypertension, Portal complications, Hypertension, Portal diagnosis, Varicose Veins
- Abstract
We report a case of anorexia nervosa (AN) with gastroesophageal varices (GEV) in a 36-year-old woman. The patient presented to our hospital with progressive bloating due to severe ascites. She had no history of alcohol intake. Esophagogastroduodenoscopy and enhanced computed tomography revealed GEV and multiple hepatic nodules, respectively. The histological examination of a liver biopsy specimen revealed similar features to nonalcoholic fatty liver disease and showed hyperplastic nodules that were suspected to be related to the uneven distribution of portal blood flow in the liver. In conclusion, patients with long-term AN should undergo abdominal imaging to detect signs of portal hypertension.
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- 2021
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23. Irsogladine maleate alters expression of a tight junction protein in portal hypertensive gastropathy.
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Yokoyama K, Irie M, Tsuchiya N, Yamauchi E, Kawashima M, Miyayama T, Fukuda H, Yamauchi R, Umeda K, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Adult, Aged, Blotting, Western methods, Edema genetics, Female, Humans, Male, Middle Aged, Pilot Projects, Stomach Diseases genetics, Claudin-3 genetics, Claudin-3 metabolism, Edema drug therapy, Edema etiology, Gastric Mucosa metabolism, Gene Expression drug effects, Hypertension, Portal complications, Stomach Diseases drug therapy, Stomach Diseases etiology, Tight Junction Proteins genetics, Tight Junction Proteins metabolism, Triazines administration & dosage, Triazines pharmacology
- Abstract
Background and Aim: Portal hypertensive gastropathy (PHG) is characterized by noninflammatory edema and vasodilatation of the lamina propria of the mucosal epithelium. In addition, the alterations of intercellular junction proteins and dilatation of the endothelial gaps have been reported. In this study, we examined whether irsogladine maleate (IM), a gastric mucosal protective agent, has the potential to improve PHG by restoration of tight junctions (TJs)., Methods: Twenty-four patients with PHG were registered and randomly assigned into two groups: 12 patients in the IM-administration group and 12 patients in the non-administration group. In the administration group, IM (4 mg/day) was administered orally for 12 weeks. Gastric mucosa with a red color in patients with PHG were obtained endoscopically on the registration day and 12 weeks later. The endoscopic findings were evaluated, an immunohistochemical analysis of claudin-3 (a TJ protein) expression in gastric mucosal tissues by a laser microscope was performed, and claudin-3 expression was quantified by western blot analysis., Results: Irsogladine maleate improved the degree of PHG in 2/12 patients endoscopically, in contrast to none of the 12 patients in the non-administration group. Immunohistochemical analysis showed that expression of claudin-3 increased in 8/12 patients in the IM-administration group and 2/12 patients in the non-administration group (P = 0.036). Western blot analysis revealed that the increase in claudin-3 after 12 weeks was significantly higher in the IM-administration group than in the non-administration group (P = 0.010)., Conclusions: The present pilot study suggested that IM might improve the gastric mucosa in PHG through restoration of TJ-protein claudin-3., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2021
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24. Elobixibat, an ileal bile acid transporter inhibitor, ameliorates non-alcoholic steatohepatitis in mice.
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Yamauchi R, Takedatsu H, Yokoyama K, Yamauchi E, Kawashima M, Nagata T, Uchida Y, Kitaguchi T, Higashi T, Fukuda H, Tsuchiya N, Takata K, Tanaka T, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Animals, Carrier Proteins, Disease Models, Animal, Ileum, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Dipeptides therapeutic use, Non-alcoholic Fatty Liver Disease drug therapy, Thiazepines therapeutic use
- Abstract
Background: Recent studies have suggested that several types of toxic bile acids (BAs) are involved in the pathogenesis of non-alcoholic steatohepatitis (NASH). In the present study, we aimed to determine whether elobixibat, an ileal bile acid transporter (IBAT) inhibitor, would ameliorate NASH in mice., Methods: C57BL/6N mice were fed a methionine and choline-deficient (MCD) to induce NASH or standard diet as control for 8 weeks (n = 5 per group). The MCD diet-fed mice were administered elobixibat 5 days a week for 4 weeks by gavage (n = 5). The effects of the treatments on liver histopathology, proinflammatory cytokine concentrations, intestinal epithelial tight junctions, and the intestinal microbial composition were then assessed., Results: In MCD-fed mice, hepatic fibrosis and inflammatory cell infiltration developed, and the serum aspartate transaminase activity and BA concentration were higher than the control. In addition, the proinflammatory cytokine concentrations were high in the liver and mesenteric lymph nodes (MLN), and the expression of intestinal epithelium tight junction proteins, claudin1, was increased. In the intestinal microbial composition, the abundance of the Lachnospiraceae and Ruminococcaeae were decreased, whereas that of the Enterobacteriaceae was increased. Treatment with elobixibat reduced the serum BA and increased the fecal BA concentration, and ameliorated the liver inflammation and fibrosis. It also reduced the expression of proinflammatory cytokines in the liver and MLNs, and transforming growth factor-β expression in the liver. Finally, elobixibat normalized intestinal tight junction protein level and the composition of the intestinal microbiota., Conclusion: Elobixibat ameliorates NASH-related histopathology, reduces cytokine expression, and normalizes the intestinal microbial composition in MCD-fed mice, which suggests that it may represent a promising candidate for the therapy of NASH.
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- 2021
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25. Novel Endoscopic Therapy for Gastric Varices Using Direct Forward-Viewing Endoscopic Ultrasonography.
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Yokoyama K, Miyayama T, Uchida Y, Fukuda H, Yamauchi R, Tsuchiya N, Umeda K, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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Gastric varices (GV) carry a high risk of massive hemorrhage because of potential rupture. To reduce the risk associated with GV, patients need to undergo hemostatic and preventive treatment. The objective of this retrospective study was to evaluate the usefulness of a new method, direct forward-viewing endoscopic ultrasonography (DFV-EUS) for the treatment of GV. We performed endoscopic injection sclerotherapy with histoacryl (EIS-HA) using DFV-EUS for GV in four patients. The paracentesis success rate was 75% (3/4). DFV-EUS has a significant advantage for the treatment of GV in that it can show physicians endoscopic and ultrasound views in real time during the delivery of the sclerosant into the GV. However, the proper use of the ultrasound view must be elucidated through further research for safer and more effective therapy. In the presence of distance between the mucosal surface and vascular lumen or when the blood flow site requires puncture as an additional treatment, DFV-EUS might be a good candidate for the treatment of GV. Altogether, EIS-HA with DFV-EUS might be a new therapeutic option for patients with GV., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)
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- 2021
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26. Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B.
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Matsumoto A, Nishiguchi S, Enomoto H, Tanaka Y, Shinkai N, Okuse C, Kang JH, Matsui T, Miyase S, Yatsuhashi H, Nagaoka S, Kanda T, Enomoto M, Yamada R, Hiramatsu N, Saito S, Takaguchi K, Ito K, Masaki T, Morihara D, Tsuge M, Chayama K, Ikeda F, Kagawa T, Kondo Y, Murata K, and Tanaka E
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- Adult, Cohort Studies, Drug Therapy, Combination, Female, Follow-Up Studies, Hepatitis B Core Antigens blood, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic blood, Hepatitis B, Chronic virology, Humans, Japan, Male, Middle Aged, Pilot Projects, Prospective Studies, Recombinant Proteins administration & dosage, Antiviral Agents administration & dosage, Hepatitis B, Chronic drug therapy, Interferon-alpha administration & dosage, Polyethylene Glycols administration & dosage, Tenofovir administration & dosage
- Abstract
Background: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179)., Methods: Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements., Results: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg., Conclusions: TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate.
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- 2020
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27. Hepatitis B virus core-related antigen is useful for surveillance of hepatocellular carcinoma recurrence in a patient with occult hepatitis B virus infection: Case report.
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Yokoyama K, Yamauchi E, Uchida Y, Kitaguchi T, Fukuda H, Yamauchi R, Tsuchiya N, Umeda K, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
- Abstract
Serum HBV core-related antigen (HBcrAg) is useful for detecting HCC in patients with occult HBV infection. Surveillance for HCC is needed in patients who are positive for HBcrAg, even if they are negative for HBsAg and HBV DNA., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)
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- 2020
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28. Horizontal Transmission of Hepatitis B Virus Genotype C Among Members of a Wrestling Club in Japan.
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Takata K, Yamauchi E, Shakado S, Uehara Y, Fukuda H, Yamauchi R, Tsuchiya N, Kunimoto H, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Sakisaka S, and Hirai F
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- Adult, DNA, Viral genetics, Genotype, Hepatitis B virus genetics, Humans, Japan, Male, Phylogeny, Young Adult, Hepatitis B, Wrestling
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BACKGROUND In adulthood, most cases of acute hepatitis B virus (HBV) infection are transmitted either by sexual contact or by contaminated needles, but there are other modes of transmission. We report on three cases of HBV infection among members of a wrestling club. CASE REPORT A 19-year-old male wrestling athlete was admitted with acute hepatitis B. Five months later, 2 other men, who were members of the same wrestling club, were diagnosed with HBV infection. The full-length sequences of the HBV DNA were identical in all three cases and classified as subgenotype C2 on phylogenetic analysis. This is the most common genotype found in Japan. No history of sexual or bleeding contact with acquaintances outside the club was noted in any of these cases. This suggests horizontal transmission within the wrestling club. CONCLUSIONS The possibility of HBV transmission through bleeding wounds and sweat is a concern in contact sports such as wrestling. Hence, hepatitis B vaccination is recommended for unvaccinated contact-sports players.
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- 2020
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29. Two Cases of Hepatocellular Carcinoma Arising Over 20 Years after a Sustained Virologic Response Following Interferon Therapy for Chronic Hepatitis C.
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Takata K, Ishii F, Uchida Y, Fukuda H, Yamauchi R, Umeda K, Tsuchiya N, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Aged, Aged, 80 and over, Carcinoma, Hepatocellular pathology, Humans, Liver Neoplasms pathology, Male, Sustained Virologic Response, Antiviral Agents therapeutic use, Carcinoma, Hepatocellular etiology, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Interferons therapeutic use, Liver Neoplasms etiology
- Abstract
The development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) due to interferon (IFN) therapy for hepatitis C virus infection remains a serious problem. We herein report 2 cases of HCC that developed more than 20 years after SVR with IFN therapy for chronic hepatitis C. The patients were 89- and 72-year-old men with HCC that developed 24-25 years after an SVR with IFN therapy. These patients regularly underwent imaging examinations; therefore, the HCC was detected in the early stage, when it was still curable. Both cases suggest that long-term surveillance after an SVR is effective for the detection of HCC, and radical treatment is possible.
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- 2020
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30. Hepatitis B Virus Reactivation after Receiving Cancer Chemotherapy under Administration of Leuprorelin Acetate.
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Yamauchi R, Takeyama Y, Takata K, Fukunaga A, Sakurai K, Tanaka T, Fukuda H, Fukuda S, Kunimoto H, Umeda K, Morihara D, Yokoyama K, Irie M, Shakado S, Sakisaka S, and Hirai F
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- Aged, 80 and over, Cyclophosphamide adverse effects, Diagnosis, Differential, Doxorubicin adverse effects, Hepatitis B virology, Humans, Male, Prednisone adverse effects, Rituximab adverse effects, Vincristine adverse effects, Virus Activation, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hepatitis B diagnosis, Hepatitis B virus physiology, Leuprolide adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
An 88-year-old man was admitted for elevated liver enzyme levels. Nine years earlier, the patient had been diagnosed with diffuse large B-cell lymphoma (DLBCL) and undergone rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone (R-CHOP) therapy. This patient previously had had a hepatitis B virus (HBV) infection before chemotherapy. After the chemotherapy, he was administered an luteinizing hormone-releasing hormone (LHRH) agonist for prostate cancer. We diagnosed him with HBV reactivation because of positive serum HBV-DNA. HBV reactivation can occur a long time after chemotherapy, particularly if another treatment with immunity-altering drugs is added. In such cases, additional surveillance may be required to detect HBV reactivation.
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- 2020
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31. Unresectable Ectopic Hepatocellular Carcinoma Treated with Sorafenib.
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Ko YL, Takata K, Tanaka T, Ohishi J, Takeshita M, Yamauchi R, Fukuda H, Miyayama T, Uchida Y, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
- Abstract
Ectopic hepatocellular carcinoma (HCC) is a rare malignancy, which manifests similar morphology and immunohistochemistry to intrahepatic HCC. Herein, we report a case of ectopic HCC in a 73-year-old male. The patient presented to our hospital with gradually progressing right lower abdominal pain, and enhanced computed tomography revealed multiple nodules in the peritoneum without intrahepatic mass. A diagnostic laparoscopy was performed, and the final pathology result confirmed that it was HCC. Additional laboratory tests showed elevated serum alpha-fetoprotein and protein induced by vitamin K absence-II (PIVKA-II) levels, suggesting our diagnosis. The patient received sorafenib, a tyrosine kinase inhibitor (TKI), for unresectable ectopic HCC. However, the tumor progressed, and because of tarry stools and hemorrhagic anemia, sorafenib was ceased after 7 months of therapy. One month after the cessation of sorafenib, the PIVKA-II level increased abruptly, and the patient died 1 year after diagnosis. The effective treatment for unresectable ectopic HCC is still unknown. Additional cases should be accumulated to determine the effect of TKI on ectopic HCC., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)
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- 2020
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32. The Efficacy and Therapeutic Outcome of Bipolar Radiofrequency Ablation for the Treatment for Hepatocellular Carcinoma in the Real-World Setting, Compared with Monopolar Radiofrequency Ablation Conducted during the Same Period.
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Tanaka T, Takata K, Kunimoto H, Fukuda H, Yamauchi R, Tsuchiya N, Inomata S, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Adult, Aged, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Disease Progression, Female, Humans, Liver diagnostic imaging, Liver metabolism, Liver pathology, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local radiotherapy, Tomography, X-Ray Computed, Treatment Outcome, alpha-Fetoproteins genetics, Carcinoma, Hepatocellular radiotherapy, Catheter Ablation methods, Liver Neoplasms radiotherapy, Radiofrequency Ablation methods
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Background: Several reports have suggested that the bipolar radiofrequency ablation (RFA) system is useful for the treatment of hepatocellular carcinoma (HCC). We evaluated the efficacy and safety of the bipolar RFA system for HCC treatment in the real-world setting., Methods: A total of 155 patients with 224 HCC tumors were enrolled. First, we examined the characteristics and outcomes of two RFA systems, monopolar and bipolar. Second, we identified the factors associated with local tumor progression in 72 patients with 104 HCC tumors, who could be followed up for at least 3 months after treatment and had been treated with the bipolar RFA system., Results: Of the baseline characteristics, tumor size and location were associated with the selection of the bipolar RFA system. A sufficient ablative zone margin (≥5 mm) was obtained by bipolar RFA in 81 of 94 (86.1%). The 1- and 2-year local tumor progression rates were 15.6 and 26.3%, respectively. An alpha-fetoprotein-L3 (AFP-L3) ratio >10% (HR: 7.64; 95% CI: 1.7-39.8, p = 0.007) and an insufficient ablative zone margin (<5 mm) (HR: 4.53; 95% CI: 1.02-20.3, p = 0.047) were related to local tumor progression in Cox regression analysis. Although severe adverse events were not observed in most cases, severe hepatic infarction occurred in 1 patient., Conclusions: The bipolar RFA system is safe and effective for HCC treatment. Tumor localization within the liver is an important factor associated with bipolar RFA. Careful follow-up or reconsideration of treatment is necessary for cases with AFP-L3 ratio >10% or insufficient ablative zone margin (<5 mm), which were associated with local tumor progression., (© 2020 S. Karger AG, Basel.)
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- 2020
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33. Reduction in Tumor Stain at 2 Weeks after Treatment Initiation Is a Predictor of the Efficacy of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma.
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Kunimoto H, Shakado S, Tanaka T, Takata K, Yamauchi R, Fukuda H, Tsuchiya N, Yokoyama K, Morihara D, Takeyama Y, Hirai F, and Sakisaka S
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- Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Biomarkers blood, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular diagnostic imaging, Female, Humans, Liver Neoplasms blood, Liver Neoplasms diagnostic imaging, Male, Middle Aged, Prospective Studies, Protein Kinase Inhibitors therapeutic use, Protein Precursors blood, Prothrombin, Response Evaluation Criteria in Solid Tumors, Staining and Labeling methods, Tomography, X-Ray Computed, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Phenylurea Compounds therapeutic use, Quinolines therapeutic use
- Abstract
Background and Aims: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks., Patients and Methods: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines., Results: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation., Conclusion: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC., (© 2020 S. Karger AG, Basel.)
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- 2020
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34. Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension.
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Yokoyama K, Tsuchiya N, Yamauchi R, Miyayama T, Uchida Y, Shibata K, Fukuda H, Umeda K, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, Sakisaka S, and Hirai F
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- Adult, Bacteria genetics, Bifidobacterium isolation & purification, Clostridium isolation & purification, Esophageal and Gastric Varices etiology, Female, Humans, Hypertension, Portal etiology, Intestines microbiology, Male, Middle Aged, Probiotics therapeutic use, RNA, Bacterial analysis, RNA, Ribosomal, 16S analysis, Streptococcus isolation & purification, Bacteria isolation & purification, Gastrointestinal Microbiome, Hypertension, Portal microbiology, Liver Cirrhosis complications
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Objective The relationship between gut microbiota and portal hypertension remains unclear. We investigated the characteristics of the gut microbiota in portal hypertension patients with esophago-gastric varices and liver cirrhosis. Methods Thirty-six patients (12 patients with portal hypertension, 12 healthy controls, and 12 non-cirrhosis patients) were enrolled in this university hospital study. Intestinal bacteria and statistical analyses were performed up to the genus level using the terminal restriction fragment length polymorphism method targeting 16S ribosomal RNA genes, with diversified regions characterizing each bacterium. Results Levels of Lactobacillales were significantly higher (p=0.045) and those of Clostridium cluster IV significantly lower (p=0.014) in patients with portal hypertension than in other patients. This Clostridium cluster contains many butanoic acid-producing strains, including Ruminococcace and Faecalibacterium prausnitzii. Clostridium cluster IX levels were also significantly lower (p=0.045) in portal hypertension patients than in other patients. There are many strains of Clostridium that produce propionic acid, and the effects on the host and the function of these bacterial species in the human intestine remain unknown. Regarding the Bifidobacterium genus, which is supposed to decrease as a result of cirrhosis, no significant decrease was observed in this study. Conclusion In the present study, we provided information on the characteristics of the gut microbiota of portal hypertension patients with esophago-gastric varices due to liver cirrhosis. In the future, we aim to develop probiotic treatments following further analyses that include the species level, such as the intestinal flora analysis method and next-generation sequencers.
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- 2020
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35. IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.
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Morihara D, Ko YL, Shibata K, Yamauchi R, Fukuda H, Tsuchiya N, Fukunaga A, Kunimoto H, Iwashita H, Takata K, Tanaka T, Sakurai K, Inomata S, Yokoyama K, Nishizawa S, Takeyama Y, Irie M, Shakado S, Sohda T, and Sakisaka S
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- Aged, Female, Hepatitis C blood, Humans, Male, Middle Aged, Antiviral Agents therapeutic use, Cholesterol, LDL blood, Hepatitis C drug therapy, Hepatitis C genetics, Interferons genetics, Polymorphism, Genetic
- Abstract
Background: Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment., Methods: A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics., Results: A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001)., Conclusions: An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2019
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36. Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents.
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Inomata S, Anan A, Yamauchi E, Yamauchi R, Kunimoto H, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Irie M, Shakado S, Sohda T, and Sakisaka S
- Subjects
- Adult, Aged, Benzimidazoles therapeutic use, Female, Fluorenes therapeutic use, Hepacivirus isolation & purification, Hepatitis C, Chronic blood, Hepatitis C, Chronic complications, Hepatitis C, Chronic virology, Humans, Iron blood, Iron Overload blood, Iron Overload virology, Male, Middle Aged, Prospective Studies, Sofosbuvir, Uridine Monophosphate analogs & derivatives, Uridine Monophosphate therapeutic use, Antiviral Agents therapeutic use, Ferritins blood, Hepatitis C, Chronic drug therapy, Hepcidins blood, Peptide Hormones blood
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Objective Hepcidin is a master iron regulator hormone produced by the liver, but precise mechanism underlying its involvement in iron overload in hepatitis C virus (HCV) infection remains unclear. We investigated the serum hepcidin levels against iron overload before and after HCV eradication. Methods We prospectively investigated the iron metabolism characteristics in 24 patients with HCV genotype 1b infection before and after treatment. We also assessed the serum erythroferrone (ERFE) levels to investigate its association with iron metabolism changes. Patients were treated with Ledipasvir 90 mg and Sofosbuvir 400 mg once daily for 12 weeks and observed for 12 more weeks in order to evaluate their sustained virological response. Results Serum hepcidin levels at baseline were in the normal range, although serum ferritin levels were increased. After HCV eradication, both serum ferritin and hepcidin levels were significantly decreased at 24 weeks from baseline (p<0.001, p=0.006, respectively). However, the serum hepcidin-to-ferritin ratios were significantly increased (p<0.001). In addition, the serum ERFE levels were significantly decreased (p<0.001). Increases in the serum hepcidin-to-ferritin ratios were correlated with decreases in the serum ERFE levels (ρ=-0.422, p=0.039). Conclusion Serum hepcidin levels were relatively low against ferritin levels in HCV infection. However, after HCV eradication, the serum hepcidin-to-ferritin ratios were increased. These results indicate the improvement of inadequate hepcidin secretion against iron overload after HCV eradication. Downregulation of ERFE may have affected the improvement of iron metabolism.
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- 2019
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37. Endoscopic treatment or balloon-occluded retrograde transvenous obliteration is safe for patients with esophageal/gastric varices in Child-Pugh class C end-stage liver cirrhosis.
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Yokoyama K, Yamauchi R, Shibata K, Fukuda H, Kunimoto H, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, and Sakisaka S
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- Adult, Aged, Esophageal and Gastric Varices complications, Esophageal and Gastric Varices mortality, Female, Humans, Liver Cirrhosis complications, Male, Middle Aged, Risk Factors, Severity of Illness Index, Survival Rate, Balloon Occlusion, Endoscopy, Gastrointestinal, Esophageal and Gastric Varices therapy, Liver Cirrhosis pathology
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Background/aims: There is a controversy about the availability of invasive treatment for esophageal/gastric varices in patients with Child-Pugh class C (CP-C) end-stage liver cirrhosis (LC). We have evaluated the validity of invasive treatment with CP-C end-stage LC patients., Methods: The study enrolled 51 patients with CP-C end-stage LC who had undergone invasive treatment. The treatment modalities included endoscopic variceal ligation in 22 patients, endoscopic injection sclerotherapy in 17 patients, and balloon-occluded retrograde transvenous obliteration (BRTO) in 12 patients. We have investigated the overall survival (OS) rates and risk factors that contributed to death within one year after treatment., Results: The OS rate in all patients at one, three, and five years was 72.6%, 30.2%, and 15.1%, respectively. The OS rate in patients who received endoscopic treatment and the BRTO group at one, three, and five years was 67.6%, 28.2% and 14.1% and 90.0%, 36.0% and 18.0%, respectively. The average of Child-Pugh scores (CPS) from before treatment to one month after variceal treatment significantly improved from 10.53 to 10.02 (P=0.003). Three significant factors that contributed to death within one year after treatment included the presence of bleeding varices, high CPS (≥11), and high serum total bilirubin levels (≥4.0 mg/dL)., Conclusion: The study demonstrated that patients with a CPS of up to 10 and less than 4.0 mg/dL of serum total bilirubin levels may not have a negative impact on prognosis after invasive treatment for esophageal/gastric varices despite their CP-C end-stage LC.
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- 2019
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38. Hepatocellular Carcinoma Arising in a Non-cirrhotic Liver with Secondary Hemochromatosis.
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Yamauchi R, Takata K, Shinagawa Y, Tanaka T, Fukuda H, Fukuda S, Kunimoto H, Umeda K, Morihara D, Yokoyama K, Takeyama Y, Irie M, Shakado S, Mizoguchi M, Hisano S, Yoshimitsu K, and Sakisaka S
- Subjects
- Aged, Biopsy, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Catheter Ablation methods, Humans, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology, Liver Neoplasms surgery, Magnetic Resonance Imaging, Male, Myelodysplastic Syndromes complications, Risk Factors, Tomography, X-Ray Computed, Ultrasonography, Carcinoma, Hepatocellular etiology, Hemochromatosis complications, Liver Neoplasms etiology
- Abstract
A 70-year-old man was admitted for treatment of a single liver nodule that was detected by contrast-enhanced computed tomography. Twenty years earlier, the patient had been diagnosed with myelodysplastic syndrome-refractory anemia and secondary hemochromatosis but had not received erythrocyte transfusions. The current histological, computed tomography, and magnetic resonance imaging findings revealed hepatocellular carcinoma (HCC) and non-cirrhotic liver hemochromatosis. The liver tumor was treated using radiofrequency ablation therapy. Secondary hemochromatosis may be a risk factor for HCC, even if the liver is not cirrhotic. In such cases, additional surveillance may be required to detect the development of HCC.
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- 2019
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39. Autoimmune Hepatitis with Concomitant Idiopathic Thrombocytopenic Purpura Diagnosed by Transjugular Liver Biopsy.
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Fukuda H, Takata K, Kitaguchi T, Yamauchi R, Kunimoto H, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Mogi A, Kora S, Koga K, Takeshita M, Yoshimitsu K, and Sakisaka S
- Abstract
Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.
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- 2018
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40. Factors Attenuating Zinc Deficiency Improvement in Direct-Acting Antiviral Agent-Treated Chronic Hepatitis C Virus Infection.
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Ko YL, Morihara D, Shibata K, Yamauchi R, Fukuda H, Kunimoto H, Takata K, Tanaka T, Inomata S, Yokoyama K, Takeyama Y, Shakado S, and Sakisaka S
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- Aged, Female, Hepatitis C, Chronic blood, Hepatitis C, Chronic urine, Humans, Hyperuricemia, Male, Middle Aged, Retrospective Studies, Risk Factors, Zinc blood, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Zinc deficiency
- Abstract
Zinc deficiency is frequently observed in chronic liver diseases. However, no studies have focused on the zinc status in chronic hepatitis C (HCV)-infected patients receiving direct-acting antiviral agents (DAAs). In this retrospective study, we assessed the serum zinc status in DAA-treated HCV patients with sustained virologic response for over two years (Zn-2y). Ninety-five patients were enrolled, whose baseline characteristics and blood parameters at DAA therapy initiation were collected. Baseline Zn < 65 µg/dL (odds ratio (OR) = 10.56, p < 0.001) and baseline uric acid (UA) > 5.5 mg/dL (OR = 9.99, p = 0.001) were independent risk factors for Zn-2y deficiency. A decision-tree algorithm classified low-baseline Zn and high-baseline UA as the first two variables, suggesting that baseline hypozincemia and hyperuricemia are prognosticators for long-term zinc deficiency. Baseline Zn was negatively correlated with the Fibrosis-4 (FIB-4) index, while baseline UA was significantly higher in habitual alcohol drinkers. In conclusion, serum zinc levels should be closely monitored, considering that zinc status improvement is related to liver fibrosis regression. Hyperuricemia indicates risks of developing metabolic disorders and subsequent zinc deficiency, for which an adjustment of personal lifestyle or dietary habits should be recommended clinically.
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- 2018
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41. Fitz-Hugh-Curtis syndrome in a man positive for Chlamydia trachomatis.
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Takata K, Fukuda H, Umeda K, Yamauchi R, Fukuda S, Kunimoto H, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Irie M, Shakado S, and Sakisaka S
- Subjects
- Abdominal Pain microbiology, Anti-Bacterial Agents therapeutic use, Anti-Ulcer Agents therapeutic use, Chlamydia Infections microbiology, Drug Therapy, Combination, Duodenal Ulcer diagnosis, Duodenal Ulcer microbiology, Hepatitis microbiology, Humans, Levofloxacin therapeutic use, Male, Middle Aged, Omeprazole therapeutic use, Pelvic Inflammatory Disease microbiology, Peritonitis microbiology, Urine microbiology, Chlamydia Infections diagnosis, Chlamydia trachomatis isolation & purification, Hepatitis diagnosis, Pelvic Inflammatory Disease diagnosis, Peritonitis diagnosis
- Abstract
Fitz-Hugh-Curtis syndrome (FHCS) is characterized by perihepatic and pelvic inflammation and occurs mostly in women of childbearing age. Here, we report a case of FHCS caused by Chlamydia trachomatis in a 50-year-old man. The patient presented to our hospital with right upper quadrant abdominal pain, and enhanced computed tomography revealed perihepatic and pelvic free fluid and early-phase hepatic capsular enhancement. A urine specimen was positive for Chlamydia trachomatis. The patient was diagnosed with FHCS due to Chlamydia trachomatis infection. In conclusion, FHCS cannot be excluded when men present with right upper quadrant abdominal pain without significant signs of biliary tract disease.
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- 2018
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42. Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy.
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Matsumoto A, Nishiguchi S, Enomoto H, Kang JH, Tanaka Y, Shinkai N, Kurosaki M, Enomoto M, Kanda T, Yokosuka O, Yatsuhashi H, Nagaoka S, Okuse C, Kagawa T, Mine T, Takaguchi K, Saito S, Hino K, Ikeda F, Sakisaka S, Morihara D, Miyase S, Tsuge M, Chayama K, Hiramatsu N, Suzuki Y, Murata K, and Tanaka E
- Subjects
- Adenine analogs & derivatives, Adenine therapeutic use, Adult, Aged, Aged, 80 and over, Antiviral Agents administration & dosage, Biomarkers blood, Drug Administration Schedule, Drug Monitoring methods, Drug Therapy, Combination, Female, Hepatitis B, Chronic virology, Humans, Interferon-alpha administration & dosage, Male, Middle Aged, Organophosphonates therapeutic use, Polyethylene Glycols administration & dosage, Prospective Studies, Recombinant Proteins administration & dosage, Recombinant Proteins therapeutic use, Antiviral Agents therapeutic use, Hepatitis B Core Antigens blood, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic drug therapy, Interferon-alpha therapeutic use, Polyethylene Glycols therapeutic use
- Abstract
Background: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy., Methods: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks., Results: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels., Conclusions: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.
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- 2018
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43. Hepatic Pseudolymphoma with an Occult Hepatitis B Virus Infection.
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Kunimoto H, Morihara D, Nakane SI, Tanaka T, Yokoyama K, Anan A, Takeyama Y, Irie M, Shakado S, Noritomi T, Takeshita M, Yoshimitsu K, and Sakisaka S
- Subjects
- Carcinoma, Hepatocellular, Female, Hepatitis B, Hepatitis B Surface Antigens, Humans, Liver Neoplasms diagnosis, Liver Neoplasms pathology, Magnetic Resonance Imaging, Middle Aged, Pseudolymphoma diagnosis, Pseudolymphoma pathology, Tomography, X-Ray Computed, Liver Neoplasms complications, Liver Neoplasms virology, Pseudolymphoma complications, Pseudolymphoma virology
- Abstract
A 49-year-old woman who was asymptomatic was found to have a small liver tumor on abdominal ultrasonography (US) at her annual health checkup. US revealed a hypoechoic, solid, mass measuring 17-mm in size in segment 6. The tumor markers associated with liver malignancy were negative. An infectious disease screen was negative for hepatitis B surface antigen, but positive for antibody to hepatitis B core antigen. Imaging studies using computed tomography (CT), magnetic resonance imaging (MRI), and CT angiography suggested a malignant liver tumor, such as hepatocellular carcinoma. Partial hepatic resection of the posterior segment was performed. The pathological diagnosis was pseudolymphoma of the liver.
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- 2018
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44. Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients.
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Takeyama Y, Uehara Y, Anan A, Morihara D, Yokoyama K, Takata K, Tanaka T, Irie M, Iwata K, Shakado S, Sohda T, and Sakisaka S
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- ATP Binding Cassette Transporter 1 antagonists & inhibitors, ATP Binding Cassette Transporter 1 metabolism, Animals, Biological Transport, Cell Line, Tumor, Cholestasis, Intrahepatic metabolism, Cholestasis, Intrahepatic pathology, Disease Models, Animal, Gene Expression Regulation, Hepatocytes metabolism, Hepatocytes pathology, Humans, Hypercholesterolemia metabolism, Hypercholesterolemia pathology, Liver pathology, Liver Cirrhosis, Biliary metabolism, Liver Cirrhosis, Biliary pathology, Liver X Receptors genetics, Liver X Receptors metabolism, Male, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Rats, Rats, Wistar, Signal Transduction, ATP Binding Cassette Transporter 1 genetics, Cholestasis, Intrahepatic genetics, Cholesterol metabolism, Hypercholesterolemia genetics, Liver metabolism, Liver Cirrhosis, Biliary genetics
- Abstract
Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (P < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (P < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (P < 0.05). The level of hepatic liver X receptor (LXR)β mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.
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- 2017
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45. Efficacy of sofosbuvir and ledipasvir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.
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Sohda T, Yokoyama K, Yamauchi E, Anan A, Tanaka T, Morihara D, Takeyama Y, Irie M, Shakado S, and Sakisaka S
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- 2017
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46. Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.
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Takata K, Shakado S, Sakamoto K, Fukuda H, Yamauchi R, Fukuda S, Kunimoto H, Umeda K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Irie M, and Sakisaka S
- Subjects
- Hepatitis C, Chronic diagnostic imaging, Humans, Liver diagnostic imaging, Male, Middle Aged, Porphyria Cutanea Tarda diagnostic imaging, Sofosbuvir, Uridine Monophosphate therapeutic use, Antiviral Agents therapeutic use, Benzimidazoles therapeutic use, Fluorenes therapeutic use, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Porphyria Cutanea Tarda drug therapy, Porphyria Cutanea Tarda etiology, Uridine Monophosphate analogs & derivatives
- Abstract
Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.
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- 2017
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47. Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.
- Author
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Sohda T, Yamauchi E, Anan A, Yokoyama K, Fukunaga A, Yamauchi R, Fukuda S, Takata K, Tanaka T, Hanano T, Kitamura Y, Morihara D, Takeyama Y, Irie M, Shakado S, and Sakisaka S
- Abstract
Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2., (© 2016 The Japan Society of Hepatology.)
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- 2017
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48. The Rate of Referral of Hepatitis Virus Carriers to Hepatologists and the Factors Contributing to Referral.
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Takata K, Anan A, Morihara D, Yotsumoto K, Sakurai K, Fukunaga A, Tanaka T, Yokoyama K, Takeyama Y, Irie M, Shakado S, Sohda T, and Sakisaka S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alanine Transaminase, Carrier State, Female, Gastroenterologists, Hepatitis B immunology, Hepatitis B Surface Antigens immunology, Hepatitis B virus immunology, Hepatitis C immunology, Humans, Male, Middle Aged, Young Adult, Hepatitis B diagnosis, Hepatitis B therapy, Hepatitis C diagnosis, Hepatitis C therapy, Referral and Consultation statistics & numerical data
- Abstract
Objective The aims of the present study were to determine the proportions of hepatitis B surface antigen (HBsAg)-positive and anti-hepatitis C virus (HCV)-positive patients, and identify the characteristics that influenced referral to a hepatologist. Methods The present study included patients who were positive for HBsAg (n=153) or anti-HCV (n=574); their viral status was tested by non-hepatologists between January 2008 to December 2012. We performed a multivariate analysis to investigate the factors associated with the referral of patients to hepatologists. Results The rates of hepatitis B virus (HBV) and the percentage of suspected HCV carriers at the hospital were 1.4% and 3.5%, respectively. Among the 727 patients who were seropositive for HBV or HCV, 107 (14.7%) were referred to a hepatologist. A multivariate analysis to investigate the factors contributing to referral revealed that (i) an alanine aminotransferase (ALT) level of >30 IU/L [odds ratio (OR), 3.24; 95% confidence interval (CI), 2.10-5.03; p<0.001]; (ii) undergoing testing at an internal medicine department (OR, 2.79; 95% CI, 1.80-4.38; p<0.001); and (iii) HBsAg-positivity (OR, 2.22; 95% CI, 1.35-3.61; p=0.002) were factors that significantly influenced referral. Conclusion Hepatologists must educate non-hepatologists, especially non-internists, to promote the referral of hepatitis-virus carriers, especially HCV carriers, even in patients with ALT levels of <30 IU/L.
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- 2017
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49. MR Imaging of a Methotrexate-associated Diffuse Large B-cell Lymphoma in the Liver that Regressed without Treatment.
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Morikawa S, Morita A, Fujimitsu R, Kuroki Y, Urakawa H, Shinagawa Y, Morihara D, Aoki M, and Yoshimitsu K
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- 2016
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50. Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease.
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Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, and Sakisaka S
- Abstract
Background and Aims: Insulin resistance and cytokine production are key mechanisms leading to fatty change in the liver and may produce nonalcoholic steatohepatitis (NASH). Oxidative stress may also contribute to clinical progression from simple fatty liver (FL) to NASH. A therapy for insulin resistance and antioxidant has been applied to treat NASH, yet these treatments are not fully established. In the present study, we have evaluated whether an antioxidant agent, glutathione, prevents the development of NASH from FL., Materials and Methods: Five patients with FL and 10 with NASH were enrolled in the study. Three hundred milligrams per day of glutathione was given orally to patients with nonalcoholic fatty liver disease (NAFLD) every day, and an oxidative stress marker and biochemical tests were analyzed before treatment and 1 and 3 months after starting the treatment. We measured serum levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and gamma-glutamyltranspeptidase (GGT). Immunohistochemistry for glutathione was performed on formalin fixed liver specimens obtained from liver biopsies., Results: Before treatment, the NASH group had higher serum 8-OHdG and lower serum glutathione levels than the FL group. Immunohistochemistry revealed that a strong expression of glutathione was observed in zone 3 in both NASH and FL before treatment. Serum levels of alanine transaminase and 8-OHdG were significantly decreased after treatment in the NASH group. Gamma-glutamyltranspeptidase was decreased after treatment, although the decrease was statistically not significant., Discussion: The present pilot study demonstrated that antioxidant therapy with glutathione may reduce the pathological oxidative stress in the liver in NASH, preventing the progression from NAFLD to NASH., How to Cite This Article: Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S. Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(1):13-18., Competing Interests: Source of support: Nil Conflict of interest: None
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- 2016
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