Publications by authors named "Hidenao Noritake"

20 Publications

  • Page 1 of 1

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Hepatol Commun 2022 Mar 28. Epub 2022 Mar 28.

Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.
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http://dx.doi.org/10.1002/hep4.1941DOI Listing
March 2022

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

Clin Gastroenterol Hepatol 2022 Jan 17. Epub 2022 Jan 17.

Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background & Aims: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
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http://dx.doi.org/10.1016/j.cgh.2022.01.002DOI Listing
January 2022

Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case-control study.

J Gastroenterol 2022 01 18;57(1):19-29. Epub 2021 Nov 18.

Teikyo Academic Research Center, Teikyo University, Tokyo, Japan.

Background: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan.

Methods: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis.

Results: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors.

Conclusions: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.
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http://dx.doi.org/10.1007/s00535-021-01836-6DOI Listing
January 2022

Azathioprine-induced severe myelosuppression accompanied by massive hair loss and painful oral ulcer in an autoimmune hepatitis patient with minor variant: A case report.

Clin Case Rep 2021 Aug 25;9(8):e04696. Epub 2021 Aug 25.

Division of Hepatology Department of Internal Medicine Hamamatsu University School of Medicine Hamamatsu Japan.

This report highlights azathioprine-induced severe myelosuppression in the patient with NUDT15 minor variant. This case report is particularly instructive because several typical symptoms are the clues to this critical adverse drug reaction.
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http://dx.doi.org/10.1002/ccr3.4696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385330PMC
August 2021

The ursodeoxycholic acid response score predicts pathological features in primary biliary cholangitis.

Hepatol Res 2021 Jan 12;51(1):80-89. Epub 2020 Dec 12.

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa.

Aim: The ursodeoxycholic acid response score (URS) can predict the biochemical response to 12 months of ursodeoxycholic acid (UDCA) treatment in patients with primary biliary cholangitis (PBC). We investigated the relationship between the URS and the histopathological features before and after UDCA treatment.

Methods: Patients with PBC (n = 126) were examined for the association between the probability of response (POR) to UDCA based on the URS formulas and clinicopathological features. Furthermore, 30 patients were examined for the association between the POR and pathological changes.

Results: The POR area under the receiver operating characteristic curve (AUROC) for predicting the biochemical response to UDCA was 0.861. The PORs of stage 1 in the Nakanuma system and grade 0 in the CK7 grading in hepatocytes were significantly higher than those of stage 3 and grade 3, respectively. The AUROCs for the prediction of stage ≥2, stage ≥3 and stage 4 in the Nakanuma system at pretreatment were 0.592, 0.710 and 0.817, respectively. The AUROCs for the prediction of grade ≥1, grade ≥2 and grade 3 in the CK7 hepatocyte grading were 0.741, 0.824 and 0.970, respectively. Furthermore, the AUROC for predicting the histological stage progression after UDCA treatment in the Scheuer classification and the Nakanuma system were 0.712 and 0.799, respectively.

Conclusions: The URS not only predicts the biochemical response, but also reflects the Nakanuma system and the CK7 hepatocyte grading at pretreatment. This scoring system can identify an inadequate histological response to UDCA treatment in the Scheuer classification and the Nakanuma system.
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http://dx.doi.org/10.1111/hepr.13584DOI Listing
January 2021

An Inhibitor of Arginine-Glycine-Aspartate-Binding Integrins Reverses Fibrosis in a Mouse Model of Nonalcoholic Steatohepatitis.

Hepatol Commun 2019 Feb 27;3(2):246-261. Epub 2018 Dec 27.

Division of Gastroenterology and Hepatology Saint Louis University St. Louis MO.

The presence and stage of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH) is strongly associated with mortality. Thus, both preventing and reversing fibrosis are critically important approaches to prevent death or the need for liver transplantation from NASH. Recently, fibrosis in several mouse models of organ injury was shown to be prevented and reversed with the potent small molecule, arginine-glycine-aspartic acid tripeptide (RGD)-binding, integrin antagonist (3S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid (Center for World Health and Medicine [CWHM]-12). We hypothesized that RGD-binding integrins may play an important role in fibrosis progression in NASH. We assessed the efficacy of CWHM-12 in a choline deficient, amino-acid defined, high-fat diet (CDAHFD) mouse model of NASH. Mice were kept on the CDAHFD or a control diet for 10 weeks, and CWHM-12 was delivered by continuous infusion for the final 4 weeks. The parameters of NASH and liver fibrosis were evaluated before and after drug treatment. Hepatic steatosis, liver injury, and inflammation were significantly induced by the CDAHFD at week 6 and did not change by week 10. Hepatic profibrogenic gene expression was induced by the CDAHFD at week 6, further increased at week 10, and decreased by CWHM-12. Fibrosis measured by analysis of liver collagen was reduced by CWHM-12 to levels significantly less than found at 6 weeks, demonstrating the possibility of reversing already established fibrosis despite ongoing injury. Demonstrated mechanisms of the antifibrotic effect of CWHM-12 included loss of activated hepatic stellate cells through apoptosis and suppression of hepatic profibrotic signal transduction by transforming growth factor β. : RGD-binding integrins may be critical in the development of fibrosis in NASH and may represent potential targets for treating patients with NASH to reverse advanced liver fibrosis.
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http://dx.doi.org/10.1002/hep4.1298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357833PMC
February 2019

Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b.

Gut Liver 2018 Mar;12(2):201-207

Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background/aims: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated.

Methods: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV).

Results: Total, LDL-, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL- and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels.

Conclusions: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.
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http://dx.doi.org/10.5009/gnl17179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832345PMC
March 2018

[Spontaneous regression of pancreatic arteriovenous malformation under the influence of severe acute pancreatitis: a case report].

Nihon Shokakibyo Gakkai Zasshi 2017;114(11):2012-2019

Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine.

A 49-year-old man was diagnosed with severe acute pancreatitis because of pancreatic arteriovenous malformation (AVM). The pancreatic AVM spontaneously regressed during conservative treatment for severe acute pancreatitis. Transarterial embolization of an aneurysm in an artery branch flowing into the pancreatic AVM was performed using metallic coils, following amelioration of severe acute pancreatitis. The complete elimination of the pancreatic AVM was confirmed 1 year after embolization, and the patient has had no recurrence of pancreatic AVM and pancreatitis for over 6 years. Most cases of pancreatic AVMs with acute pancreatitis require surgical resection. This is a rare case in which the pancreatic AVM spontaneously regressed under the influence of acute severe pancreatitis.
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http://dx.doi.org/10.11405/nisshoshi.114.2012DOI Listing
May 2018

Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C.

J Interferon Cytokine Res 2015 Dec 26;35(12):956-62. Epub 2015 Aug 26.

3 Respiratology Division, Department of Internal Medicine, Hamamatsu University School of Medicine , Hamamatsu, Japan .

The enhanced accumulation of hepatic progenitor cells (HPCs) is related to the risk of progression to hepatocellular carcinoma (HCC). Interferon (IFN) treatment reduces HCC risk in patients with chronic hepatitis C virus (HCV) infection. However, the underlying mechanisms remain unclear. The aim of this study was to examine the effects of IFN treatment on HPC activation in HCV patients. Immunohistochemical detection and computer-assisted quantitative image analyses of cytokeratin 7 (CK7) were performed to evaluate HPC activation in paired pre- and post-treatment liver biopsies from 18 HCV patients with sustained virological response (SVR) to IFN-based therapy and from 23 patients without SVR, as well as normal liver tissues obtained from surgical resection specimens of 10 patients. Pretreatment HCV livers showed increased CK7 immunoreactivity, compared with normal livers (HCV: median, 1.38%; normal: median, 0.69%, P=0.006). IFN treatment reduced hepatic CK7 immunoreactivity (median, 1.57% pre-IFN vs. 0.69% post-IFN, P=0.006) in SVR patients, but not in non-SVR patients. The development of HCC following IFN treatment was encountered in 3 non-SVR patients who showed high post-IFN treatment CK7 immunoreactivity (>4%). Successful IFN therapy can reverse enhanced HPC activation in HCV patients, which may contribute to the reduced risk of HCC development in these patients.
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http://dx.doi.org/10.1089/jir.2014.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683555PMC
December 2015

Pol I-transcribed hepatitis C virus genome RNA replicates, produces an infectious virus and leads to severe hepatic steatosis in transgenic mice.

Biomed Res 2015 ;36(3):159-67

Department of Biochemistry, Hamamatsu University School of Medicine.

Patients chronically infected with hepatitis C virus (HCV) are at risk of developing end-stage liver disease and hepatocellular carcinoma. Development of drugs to inhibit hepatocyte damage and a vaccine against HCV is hampered by the lack of a small animal model. We generated mice in which the viral genome RNA was always present in the hepatocytes using a special transgene. Here we show that the HCV genome RNA transcribed by Pol I polymerase can replicate and produce infectious viruses in mice. We obtained a transgenic mouse with 200 copies per haploid which we named the A line mouse. It produced ~ 3 × 10(6) HCV RNA copies/mL serum, which is at the comparable level as patients with chronic HCV infection. This mouse was immunotolerant to HCV and showed hepatic steatosis without any necroinflammation at the age of 6 months or hepatocellular carcinoma at the age of 15 months. Thus, the A line mouse can be used as an animal model for chronic HCV infection. This will enable better study of the abnormalities in metabolism and signal transduction in infected hepatocytes, and development of drugs that cure abnormalities.
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http://dx.doi.org/10.2220/biomedres.36.159DOI Listing
March 2016

Long-term pegylated interferon monotherapy following 72 weeks of pegylated interferon and ribavirin in hepatitis C virus genotype-1-infected slow responders.

Intern Med 2015 ;54(3):273-9

Division of Hepatology, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Japan.

Objective: Slow responders to pegylated interferon (Peg-IFN) and ribavirin (RBV) among patients infected with hepatitis C virus (HCV) genotype 1 may benefit from an extended treatment course. The aim of this study was to determine the efficacy of persistent negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy.

Methods: A total of 46 HCV genotype 1-infected slow responders were treated for 72 weeks with Peg-IFN and RBV combination therapy alone (n=25) or additional long-term biweekly treatment with 90 μg of Peg-IFN-α2a (n=21). The criterion for the completion of long-term Peg-IFN monotherapy was defined as the attainment of constantly negative HCV RNA in the serum over 96 weeks during IFN treatment.

Results: The patients with sustained negative serum HCV RNA during 96 weeks of IFN treatment had a higher rate of sustained virological response (SVR) than those without (81 vs. 40%, p=0.012). A multivariate analysis identified sustained negativity of serum HCV RNA over 96 weeks of IFN treatment to be a predictive factor for SVR.

Conclusion: In the present study, sustained negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy of Peg-IFN and RBV resulted in beneficial virological outcomes among HCV genotype 1-infected slow responders.
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http://dx.doi.org/10.2169/internalmedicine.54.2718DOI Listing
June 2015

Improved Serum Alpha-Fetoprotein Levels after Iron Reduction Therapy in HCV Patients.

ISRN Hepatol 2014 4;2014:875140. Epub 2014 Feb 4.

Division of Respiratology, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.

Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients. Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies. Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7 ng/mL, ALT from 96 to 50 IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28 IU/L, and ferritin from 191 to 10 ng/mL (P < 0.001 for each). The rate of decline in the AFP level correlated positively only with that in GGT (r = 0.695, P = 0.001), although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10 ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30 IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5-293; P = 0.024). Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients.
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http://dx.doi.org/10.1155/2014/875140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890901PMC
June 2016

Does hepatic oxidative stress enhance activation of nuclear factor-E2-related factor in patients with nonalcoholic steatohepatitis?

Antioxid Redox Signal 2014 Jan 17;20(3):538-43. Epub 2013 Aug 17.

1 Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine , Hamamatsu, Shizuoka, Japan .

The imbalance of hepatic oxidant and antioxidant status is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). The nuclear factor-E2-related factor (Nrf2) is a key transcription factor regulating a plethora of antioxidant genes involved in antioxidant defense. To clarify the mechanisms of hepatic antioxidant defenses in human NASH, the aim of the current study was to examine oxidative stress-induced Nrf2 activation in the livers of patients with NASH. Liver biopsies were obtained from 19 NASH patients. Normal liver tissue was obtained from surgical resection specimens of 15 patients. The proportion of hepatocytes with 8-hydroxydeoxyguanosine (8-OHdG)-positive nuclei was increased in NASH livers compared with that in normal livers. Hepatic Nrf2 protein levels were increased with enhanced accumulation of hepatocellular nuclear Nrf2, which was positively correlated with that of 8-OHdG. Hepatic expression of γ-glutamylcysteine synthetase (γGCS), glutathione peroxidase 2 (GPx2), thioredoxin (TRX), and heme oxygenese 1 (HO-1), but not thioredoxin reductase 1 (TrxR1), was upregulated, and the protein levels of γGCS were positively correlated with those of Nrf2. Collectively, our findings lead to the hypothesis that oxidative stress may enhance Nrf2 activation in the livers of patients with NASH.
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http://dx.doi.org/10.1089/ars.2013.5470DOI Listing
January 2014

Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes.

Biochem Biophys Res Commun 2012 Jan 11;417(1):601-6. Epub 2011 Dec 11.

Department of Biochemistry, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.

The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with ∼50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.
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http://dx.doi.org/10.1016/j.bbrc.2011.12.014DOI Listing
January 2012

Expression of human factors CD81, claudin-1, scavenger receptor, and occludin in mouse hepatocytes does not confer susceptibility to HCV entry.

Biomed Res 2011 Apr;32(2):143-50

Department of Biochemistry, Hamamatsu University School of Medicine, Handa-yama, Higashi-ku, Hamamatsu, Shizuoka, Japan.

No suitable mouse model is available for studying chronic liver disease caused by hepatitis C virus (HCV). CD81, claudin-1, scavenger receptor class B type I, and occludin were recently reported to be the important factors in HCV entry into hepatocytes. We made transgenic mice (Alb-CCSO) expressing the four human proteins and examined whether HCV from a patient serum or HCV pseudoparticles (HCVpp) were capable of infecting them. HCV was not detected in the mouse serum after injecting the mice with HCV from a patient serum. We also found no indications of HCVpp entry into primary hepatocytes from Alb-CCSO mice. In addition, HCV-infectible Hep3B cells were fused with HCV-resistant primary mouse hepatocytes and the fused cells showed 35-fold lower infectivity compared to wild-type Hep3B cells, indicating that primary mouse hepatocytes have the inhibitory factor(s) in HCVpp entry. Our results suggest that the expression of the human factors does not confer susceptibility to HCV entry into the liver.
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http://dx.doi.org/10.2220/biomedres.32.143DOI Listing
April 2011

Hemorrhagic radiation gastritis successfully treated with repeated intra-arterial steroid infusions.

Clin J Gastroenterol 2011 Feb 10;4(1):34-8. Epub 2010 Dec 10.

Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu, Shizuoka, 431-3192, Japan.

Intra-arterial steroid infusion therapy has previously been shown to be effective for inflammatory bowel disease; however, few cases in which it has been used for the treatment of hemorrhagic radiation gastritis have been reported. We report the case of a 70-year-old Japanese man with hemorrhagic radiation gastritis induced by radiation therapy for para-aortic lymph node metastases of hepatocellular carcinoma. Two months after completing radiation therapy, acute persistent bleeding occurred in the gastric irradiation area. Although argon plasma coagulation was performed five times over a month, the bleeding continued and the patient showed persistent anemia that required 50 units of blood transfusion. Finally, the patient was given intra-arterial steroid infusions through the right gastric artery and the right gastroepiploic artery. After three intra-arterial steroid infusions, the melena stopped, and the anemia no longer progressed. Hemorrhagic radiation gastritis was successfully treated with repeated intra-arterial steroid infusions through the regional vessels to the gastric mucosa. Repeated intra-arterial steroid infusions could be a clinically useful option for the treatment of intractable bleeding from radiation gastritis.
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http://dx.doi.org/10.1007/s12328-010-0191-8DOI Listing
February 2011

A case of systemic lupus erythematosus with liver damage.

Nihon Shokakibyo Gakkai Zasshi 2010 Jun;107(6):915-22

Second Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.

A 38-year-old woman with systemic lupus erythematosus (SLE) presented with liver damage during prednisolone therapy. Because her liver damage did not improve, she was admitted to our hospital. Laboratory findings revealed liver enzyme elevation, impaired glucose tolerance, and insulin resistance. Pathological examination revealed marked diffuse macro and microvesicular fatty infiltration. Because the patient did not consume alcohol, she was given a diagnosis of nonalcoholic steatohepatitis. To improve her insulin resistance, we administered pioglitazone therapy for 1 week; however, subsequent laboratory findings did not indicate any improvement in her liver damage. Assuming that SLE might have caused liver damage, we administered high-dose prednisolone therapy; subsequent laboratory findings indicated that her serum complement titer and the level of liver enzymes improved. Abdominal computed tomography revealed that the Hounsfield number of the liver increased to normal after treatment. Fat infiltration of the liver improved after treatment, which confirmed the fact that her liver damage had been due to SLE.
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June 2010

Enhanced hepatic Nrf2 activation after ursodeoxycholic acid treatment in patients with primary biliary cirrhosis.

Antioxid Redox Signal 2010 Aug;13(3):259-68

Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.

The cytoprotective mechanisms of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC) have not been fully clarified. UDCA has some antioxidant properties. Nuclear factor-E2-related factor-2 (Nrf2) plays a critical role in protecting a variety of tissues against oxidative stress. Therefore, to investigate the potential antioxidant effects of UDCA in PBC, we determined the intracellular status of both oxidant stress and antioxidant defenses in paired pre- and posttreatment liver biopsies from 13 PBC patients by immunodetection of 8-hydroxydeoxyguanosine (8-OHdG), Nrf2-, and Nrf2-mediated antioxidant proteins. After UDCA treatment, the number of 8-OHdG-positive hepatocytes or bile duct cells decreased with improvement of hepatic injury. The hepatic levels of both total and phosphorylated Nrf2 protein were increased, along with upregulation of nuclear phosphorylated Nrf2 expression in bile duct cells. In addition, the levels of both thioredoxin (TRX) and thioredoxin reductase 1 (TrxR1) protein were increased in the liver after UDCA. The upregulation of hepatic TRX or TrxR1 protein expression positively correlated with that of total Nrf2 protein expression. In conclusion, UDCA treatment can enhance hepatic Nrf2 activation and upregulate hepatic TRX and TrxR1 protein expression. Hepatic Nrf2 activation may play a role in the therapeutic response to UDCA in PBC.
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http://dx.doi.org/10.1089/ars.2009.2903DOI Listing
August 2010

[A case of jejunal perforation in gallstone ileus].

Nihon Shokakibyo Gakkai Zasshi 2008 Apr;105(4):578-82

Department of Gastroenterology, Hamamatsu Medical Center.

Gallstone ileus is a rare but important cause of small bowel obstruction in the geriatric population. A 65-year-old man with a twenty year history of cholecystolithiasis was admitted to our hospital with abdominal pain and vomiting. Physical exams showed abdominal defence and rebound tenderness. A plain abdominal X-ray suggested a small bowel obstruction and pneumobilia. CT scan revealed a 2.5-cm gallstone at the jejunum and air in the biliary tree. The patient underwent a emergency laparotomy based on a diagnosis of panperitonitis with a perforation associated with gallstone ileus. Operative findings revealed a jejunal perforation and a impacted stone on the anal side of perforation. Enterolithotomy and jejunal resection were performed with cholecystectomy and repairment of the cholecystoduodenal fistula.
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April 2008
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