FullText URL fulltext.pdf
Author Hirai, Mami| Kinugasa, Hideaki| Nouso, Kazuhiro| Yamamoto, Shumpei| Terasawa, Hiroyuki| Onishi, Yuma| Oyama, Atsushi| Adachi, Takuya| Wada, Nozomu| Sakata, Masahiro| Yasunaka, Tetsuya| Onishi, Hideki| Shiraha, Hidenori| Takaki, Akinobu| Okada, Hiroyuki|
Keywords ctDNA hepatocellular carcinoma liquid biopsy prediction prognosis TERT promoter mutation
Published Date 2020-08-24
Publication Title Journal of Gastroenterology and Hepatology
Volume volume36
Publisher Wiley
Start Page 1118
End Page 1125
ISSN 0815-9319
NCID AA10727383
Content Type Journal Article
File Version author
PubMed ID 32830343
DOI 10.1111/jgh.15227
Web of Science KeyUT 000568136400001
Related Url isVersionOf https://doi.org/10.1111/jgh.15227
JaLCDOI 10.18926/AMO/31129
FullText URL fulltext.pdf
Author Takaki, Akinobu| Sakaguchi, Kohsaku| Ogawa, Shin| Kawamoto, Hirofumi| Tsuji, Takao|
Abstract We investigated the specificities and characteristics of anti-cytoskeleton antibodies in 13 anti-smooth muscle antibody (ASMA)-positive patients with chronic liver disease C (CLD-C), and compared them with those in 7 ASMA-positive patients with autoimmune hepatitis (AIH), and 6 ASMA-positive patients with chronic liver disease B (CLD-B). Anti-microfilaments (anti-MF) were found not only in 6/7 AIH patients (85.7%), but also in 8/13 CLD-C patients (61.5%) with a relatively high incidence, when compared with 1/6 CLD-B patients (16.7%), while, there was no significant difference in the incidence of anti-intermediate filaments (anti-IMF), especially anti-IMF IgM, among these patient groups. Among the patients with CLD-C, the mean levels of serum gammaglobulin and IgG in the anti-MF-positive patients were 2.46 +/- 1.03 g/dl and 3277 +/- 1089 mg/dl, respectively, which were higher than those in the anti-MF-negative patients (1.60 +/- 0.53 g/dl, 2245 +/- 610 mg/dl) and those in the patients with CLD-B (1.60 +/- 0.57 g/dl, 2192 +/- 339 mg/dl). Furthermore, 4 of the 8 anti-MF-positive patients with CLD-C satisfied the serological criteria for the diagnosis of AIH. These findings suggest that autoimmune mechanisms might be involved in the pathogenesis of anti-MF-positive CLD-C, and that anti-MF might be used as a marker.
Keywords chronic liver disease C autoimmune hepatitis anti-smooth muscle antibodies anti-cytoskeleton antibodies anti-microfilament antibodies
Amo Type Article
Publication Title Acta Medica Okayama
Published Date 1994-06
Volume volume48
Issue issue3
Publisher Okayama University Medical School
Start Page 143
End Page 149
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders Copyright© 1999 Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 7942072
Web of Science KeyUT A1994NV04300005
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/3090
JaLCDOI 10.18926/AMO/31549
FullText URL fulltext.pdf
Author Hino, Naoki| Higashi, Toshihiro| Ueki, Tooru| Nakatsukasa, Harushige| Ooguchi, Souhei| Ashida, Kouzou| Fujio, Kouzou| Takaki, Akinobu| Yonei, Taiji| Hasui, Toshimi| Tsuji, Hideyuki| Tsuji, Takao|
Abstract

We report here a case of hepatocellular carcinoma (HCC) with multiple lung metastases, which were disappeared by treatment of OK-432. The patient was a 65-year-old man and was diagnosed in 1986 with a small (17 x 11 mm) HCC in the anterior-superior segment of the liver. A part of the right hepatic lobe including the tumor was surgically removed, and transarterial injections of adriamycin (10 mg/week) and subcutaneous injections of OK-432 (10 KE/week) were given. Two and a half years later, recurrence of HCC in the liver and its invasion to vena cava inferior (IVC) were found. OK-432 administration was then stopped and percutaneous ethanol injection therapy (PEIT) was performed 10 times. Six months later, the PEIT was effective and the liver tumor with IVC invasion diminished. However, multiple lung metastases were visible on roentgenograms of the chest, and serum alphafetoprotein (AFP) concentration increased to 50,000 ng/ml. The OK-432 treatment resumed. After 6 months of OK-432 treatment, the multiple lung metastases were disappeared and the serum AFP level decreased to 100 ng/ml. At present, the patient is surviving without any sign of recurrence in either the liver or the lung. The clinical course of this case suggests that OK-432 might have effectively treated lung metastases of HCC, although the exact mechanisms are at present unclear.

Keywords hepatocellular carcinoma OK-432 pulmonary metastasis
Amo Type Article
Publication Title Acta Medica Okayama
Published Date 1993-08
Volume volume47
Issue issue4
Publisher Okayama University Medical School
Start Page 289
End Page 292
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
File Version publisher
Refereed True
PubMed ID 7692705
Web of Science KeyUT A1993LV73800011
JaLCDOI 10.18926/AMO/31582
FullText URL fulltext.pdf
Author Kawamoto, Hirofumi| Sakaguchi, Kohsaku| Takaki, Akinobu| Ogawa, Shin| Tsuji, Takao|
Abstract We investigated autoimmunity, as assessed by hypergammaglobulinemia and the presence of autoantibodies including anti-nuclear antibodies (ANA) and anti-liver membrane antibodies (LMA), in 149 patients with chronic hepatitis C, 55 patients with chronic hepatitis B and 11 patients with autoimmune hepatitis. There was no significant difference in the incidence of these autoantibodies between chronic hepatitis C and chronic hepatitis B. Nine patients with chronic hepatitis C satisfied the serological criteria of autoimmune hepatitis (ANA positive and gammaglobulin or serum IgG greater than 2500 mg/dl), but none of the patients with chronic hepatitis B met the criteria. This suggests that autoimmunity is greater in chronic hepatitis C than in chronic hepatitis B. Of the 9 patients with chronic hepatitis C, all 4 patients tested for human leukocyte antigen (HLA) phenotype had HLA-DR4, which is known to be associated with autoimmune hepatitis in Japanese patients. We believe that hepatitis C virus (HCV) infection enhances the initiation and perpetuation of autoimmunity in susceptible individuals.
Keywords chronic hepatitis C autoimmune hepatitis anti-nuclear antibodyies anti-liver membrane antibodies HLA
Amo Type Article
Publication Title Acta Medica Okayama
Published Date 1993-10
Volume volume47
Issue issue5
Publisher Okayama University Medical School
Start Page 305
End Page 310
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders Copyright© Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 8273454
Web of Science KeyUT A1993ME47100003
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/2332
JaLCDOI 10.18926/AMO/32813
FullText URL fulltext.pdf
Author Sawayama, Tomoyuki| Sakaguchi, Kohsaku| Senoh, Tomonori| Ohta, Takeyuki| Nishimura, Mamoru| Takaki, Akinobu| Tsuji, Takao| Shiratori, Yasushi|
Abstract

In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell activity decreases significantly, and the reduced activity may be associated with the progression of HCC. In this study we evaluated the effects of pulsing with interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the presence of IL-2 and/or IL-12. After 24 h of incubation, the levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha presented in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-gamma and TNF-alpha production of PBL pulsed by a combination of IL-2 and IL-12 was significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone. The mRNA encoding perforin, granzyme B, as well as IFN-gamma and TNF-alpha, were markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of IFN-gamma and TNF-alpha, and the expression of perforin and granzyme B mRNA in PBL obtained from HCC patients, as well as in those obtained from normal subjects. These results indicate that adoptive immunotherapy based on PBL pulsed with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for HCC treatment.

Keywords hepatocellular carcinoma(HCC) interleukin(IL)-2 interleukin(IL)-12 interferon(IFN)-r granzyme B
Amo Type Article
Publication Title Acta Medica Okayama
Published Date 2003-12
Volume volume57
Issue issue6
Publisher Okayama University Medical School
Start Page 285
End Page 292
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
File Version publisher
Refereed True
PubMed ID 14726965
Web of Science KeyUT 000187556500003
JaLCDOI 10.18926/AMO/32914
FullText URL fulltext.pdf
Author Miyake, Yasuhiro| Iwasaki, Yoshiaki| Ishikawa, Shin| Tatsukawa, Masashi| Nawa, Toru| Kato, Jun| Takaki, Akinobu| Kobashi, Haruhiko| Sakaguchi, Kohsaku| Shiratori, Yasushi|
Abstract We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofi berscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required.
Keywords hepatitis B virus genotype homosexual amebic colitis lamivudine
Amo Type Case Report
Publication Title Acta Medica Okayama
Published Date 2007-02
Volume volume61
Issue issue1
Publisher Okayama University Medical School
Start Page 35
End Page 39
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
File Version publisher
Refereed True
PubMed ID 17332840
Web of Science KeyUT 000244432400005
JaLCDOI 10.18926/AMO/43825
FullText URL 65_1_11.pdf
Author Kuwaki, Kenji| Nouso, Kazuhiro| Kobayashi, Yoshiyuki| Nakamura, Shinichiro| Ito, Yoichi M.| Iwadou, Shouta| Hagihara, Hiroaki| Yasunaka, Tetsuya| Toshimori, Junichi| Miyatake, Hirokazu| Miyoshi, Kenji| Onishi, Hideki| Miyake, Yasuhiro| Shoji, Bon| Takaki, Akinobu| Shiraha, Hidenori| Iwasaki, Yoshiaki| Kobashi, Haruhiko| Yamamoto, Kazuhide|
Abstract The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n=336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n=227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time-dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.
Keywords hepatocellular carcinoma humans prognosis proportional hazards models time factors
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2011-02
Volume volume65
Issue issue1
Publisher Okayama University Medical School
Start Page 11
End Page 19
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 21339791
Web of Science KeyUT 000287620500002
JaLCDOI 10.18926/AMO/49042
FullText URL 66_6_461.pdf
Author Koike, Kazuko| Takaki, Akinobu| Kato, Nobuyuki| Ouchida, Mamoru| Kanzaki, Hirotaka| Yasunaka, Tetsuya| Shiraha, Hidenori| Miyake, Yasuhiro| Yamamoto, Kazuhide|
Abstract Hepatitis C virus (HCV) infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE) and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their “cured” cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1), which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP), which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression.
Keywords hepatitis C virus retinol-binding protein
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2012-12
Volume volume66
Issue issue6
Publisher Okayama University Medical School
Start Page 461
End Page 468
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 23254580
Web of Science KeyUT 000312966100005
JaLCDOI 10.18926/AMO/52139
FullText URL 68_1_17.pdf
Author Moritou, Yuki| Ikeda, Fusao| Iwasaki, Yoshiaki| Baba, Nobuyuki| Takaguchi, Kouichi| Senoh, Tomonori| Nagano, Takuya| Takeuchi, Yasuto| Yasunaka, Tetsuya| Ohnishi, Hideki| Miyake, Yasuhiro| Takaki, Akinobu| Nouso, Kazuhiro| Yamamoto, Kazuhide|
Abstract The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p=0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p=0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p=0.049, and <0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy.
Keywords hepatic steatosis genetic polymorphism interferon HCV
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2014-02
Volume volume68
Issue issue1
Publisher Okayama University Medical School
Start Page 17
End Page 22
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 24553484
Web of Science KeyUT 000331592800003
JaLCDOI 10.18926/AMO/52145
FullText URL 68_1_53.pdf
Author Terasaka, Tomohiro| Ueta, Eijiro| Ebara, Hirotaka| Waseda, Koichi| Hanayama, Yoshihisa| Takaki, Akinobu| Kawabata, Tomoko| Sugiyama, Hitoshi| Hidan, Ko| Otsuka, Fumio|
Abstract A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction, hypophosphatemia and increased levels of bone alkaline phosphatase were found. The patientʼs serum creatinine level had gradually increased after the initiation of adefovir dipivoxil administration for hepatitis B. In agreement with multifocal uptakes of bone scintigraphy, iliac bone biopsy revealed an abnormal increase in osteoid tissues. Reducing the dose of adefovir and initiating the administration of eldecalcitol were effective for reducing proteinuria and glucosuria, and for ameliorating bone pain with an increase in serum phosphate level. This case first showed a clinical course of hypophosphatemic osteomalacia caused by secondary Fanconiʼs syndrome for 8 years after adefovir administration. Early diagnosis is important for the reversibility of bone damage and for a better renal prognosis.
Keywords adefovir dipivoxil (ADV) eldecalcitol Fanconi's syndrome hypophosphatemia osteomalacia
Amo Type Case Report
Publication Title Acta Medica Okayama
Published Date 2014-02
Volume volume68
Issue issue1
Publisher Okayama University Medical School
Start Page 53
End Page 56
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 24553490
JaLCDOI 10.18926/AMO/52790
FullText URL 68_4_243.pdf
Author Wada, Nozomu| Yasunaka, Tetsuya| Ikeda, Fusao| Nishina, Sohji| Korenaga, Masaaki| Hino, Keisuke| Fujioka, Shin-ichi| Osawa, Toshiya| Itoshima, Tatsuya| Kawanaka, Miwa| Yamada, Gotaro| Kariyama, Kazuya| Takayama, Hiroki| Kubota, Junichi| Morimoto, Yoichi| Mizushima, Takaaki| Yamashita, Haruhiko| Tanioka, Hiroaki| Negoro, Yuji| Toshimori, Junichi| Kobashi, Haruhiko| Hirano, Atsushi| Itano, Yasuo| Takaki, Akinobu| Yamamoto, Kazuhide|
Abstract Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p<0.01), among men who had sex with men (100%, p<0.005), and among patients having sex with unspecified partners (44.8%, p<0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A.
Keywords acute hepatitis hepatitis B virus
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2014-08
Volume volume68
Issue issue4
Publisher Okayama University Medical School
Start Page 243
End Page 247
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25145410
Web of Science KeyUT 000340687500006
JaLCDOI 10.18926/AMO/52894
FullText URL 68_5_263.pdf
Author Namba, Shihoko| Miyake, Kayoko| Ikeda, Fusao| Hazama, Tomoko| Hitobe, Yu| Yamasaki, Noriko| Shiraha, Hidenori| Takaki, Akinobu| Nouso, Kazuhiro| Iwasaki, Yoshiaki| Yamamoto, Kazuhide|
Abstract Nursing support might help patients with chronic hepatitis C (CHC) remain in good mental and physical condition during interferon (IFN) therapy. However, the effects of nursing support have not been studied adequately in this context. This case-control study evaluated the effects of nursing support during IFN therapy. Twenty-four CHC patients who received pegylated IFN and ribavirin were enrolled. Nurses advised patients on the maintenance of their mental and physical condition at weekly visits, based on the results of written questionnaires. An additional 24 patients who received IFN therapy without nursing support and who were matched for age, sex, platelet count, viral serogroup and IFN regimen were selected with propensity score matching as controls. The patients with nursing support during IFN therapy achieved higher sustained virological responses (79%) than those without nursing support (58%). Adherence to the IFN and ribavirin regimens at 24 weeks of therapy were slightly higher in the patients with nursing support than those without it, but these differences were not statistically significant. Adherence to ribavirin after 24 weeks of therapy was significantly higher in those with nursing support than those without it (93% and 66%, p=0.045). These results suggested that nursing support services could contribute to the virological responses of CHC patients by promoting drug-regimen adherence.
Keywords chronic hepatitis C nursing support interferon therapy
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2014-10
Volume volume68
Issue issue5
Publisher Okayama University Medical School
Start Page 263
End Page 268
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25338482
Web of Science KeyUT 000343269300002
JaLCDOI 10.18926/AMO/52898
FullText URL 68_5_291.pdf
Author Tsuzaki, Ryuichiro| Takaki, Akinobu| Yagi, Takahito| Ikeda, Fusao| Koike, Kazuko| Iwasaki, Yoshiaki| Shiraha, Hidenori| Miyake, Yasuhiro| Sadamori, Hiroshi| Shinoura, Susumu| Umeda, Yuzo| Yoshida, Ryuichi| Nobuoka, Daisuke| Utsumi, Masashi| Nakayama, Eiichi| Fujiwara, Toshiyoshi| Yamamoto, Kazuhide|
Abstract It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At>3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.
Keywords interferon gamma ELISPOT assay single nucleotide polymorphisms dendritic cell CD4 T cell
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2014-10
Volume volume68
Issue issue5
Publisher Okayama University Medical School
Start Page 291
End Page 302
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25338486
Web of Science KeyUT 000343269300006
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/53129
JaLCDOI 10.18926/AMO/53520
FullText URL 69_3_137.pdf
Author Seki, Hiroyuki| Ikeda, Fusao| Nanba, Shintaro| Moritou, Yuki| Takeuchi, Yasuto| Yasunaka, Tetsuya| Onishi, Hideki| Miyake, Yasuhiro| Takaki, Akinobu| Nouso, Kazuhiro| Iwasaki, Yoshiaki| Nakamura, Minoru| Yamamoto, Kazuhide|
Abstract A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patientsʼ hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis.
Keywords primary biliary cirrhosis keratin 7 hepatic failure
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2015-06
Volume volume69
Issue issue3
Publisher Okayama University Medical School
Start Page 137
End Page 144
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26101189
Web of Science KeyUT 000356903000002
JaLCDOI 10.18926/AMO/53558
FullText URL 69_4_219.pdf
Author Toshimori, Junichi| Nouso, Kazuhiro| Nakamura, Shinichiro| Wada, Nozomu| Morimoto, Yuki| Takeuchi, Yasuto| Yasunaka, Tetsuya| Kuwaki, Kenji| Ohnishi, Hideki| Ikeda, Fusao| Shiraha, Hidenori| Takaki, Akinobu| Yamamoto, Kazuhide|
Abstract We conducted a retrospective cohort study to investigate the predisposing factors for local recurrence and complications after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). HCC patients (n=397) consecutively treated with RFA (256 males, 141 females, median age 69 years) were enrolled. In these patients, 1,455 nodules (median size 17mm) were ablated. Predisposing factors for overall recurrence and local recurrence in the context of tumor location and complications were examined. Local recurrence was observed for 113 of the 1,455 nodules. The 1-, 3- and 5-year local recurrence rates were 2.2オ, 7.4オ and 9.5オ, respectively. A multivariate Cox proportional hazard analysis revealed that large tumor size (>2cm), tumor location (adjacent to the major portal branch or hepatic vein), and small ablated margin (<3mm) were independent predisposing factors for local recurrence after RFA (HR=1.70-2.81). Tumor location (adjacent to the major portal branch, hepatic vein, or diaphragm) was also revealed as a risk factor for liver damage due to RFA. HCC adjacent to the major portal vein or hepatic vein was associated with a higher risk for local recurrence and for complications;therefore, special precautions are necessary when applying RFA to HCC near vessels even when the tumors are located at an easy-to-puncture site.
Keywords hepatocellular carcinoma radiofrequency ablation ablated margin tumor location
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2015-08
Volume volume69
Issue issue4
Publisher Okayama University Medical School
Start Page 219
End Page 226
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26289913
Web of Science KeyUT 000365519100005
JaLCDOI 10.18926/AMO/53560
FullText URL 69_4_237.pdf
Author Nanba, Shintarou| Ikeda, Fusao| Fujioka, Shin-ichi| Araki, Yasuyuki| Takaguchi, Kouichi| Hashimoto, Noriaki| Seki, Hiroyuki| Takaki, Akinobu| Iwasaki, Yoshiaki| Yamamoto, Kazuhide|
Abstract The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51オ), and 89オ of them obtained sustained virological response (SVR), while 69オ of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence<80オ pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2.
Keywords hepatitis C virus interferon genotype 2 response-guided therapy
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2015-08
Volume volume69
Issue issue4
Publisher Okayama University Medical School
Start Page 237
End Page 244
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26289915
Web of Science KeyUT 000365519100007
JaLCDOI 10.18926/AMO/53996
FullText URL 70_1_1.pdf
Author Yasunaka, Tetsuya| Ikeda, Fusao| Wada, Nozomu| Morimoto, Yuki| Fujioka, Shin-ichi| Toshimori, Junichi| Kobashi, Haruhiko| Kariyama, Kazuya| Morimoto, Yoichi| Takayama, Hiroki| Seno, Tomonori| Takaguchi, Koichi| Moriya, Akio| Miyatake, Hirokazu| Okamoto, Ryoichi| Yabushita, Kazuhisa| Takaki, Akinobu| Yamamoto, Kazuhide|
Abstract Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged ≥ 35 years, HBV DNA ≥ 4 log copies/mL and positive HBeAg at diagnosis (n=184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p=0.013). Among the patients aged ≥ 35 years with HBV DNA ≥ 4 log copies/mL and negative HBeAg (n=237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p>0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged≥35 years with HBV DNA ≥4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development.
Keywords entecavir hepatitis B virus lamivudine hepatocellular carcinoma
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2016-02
Volume volume70
Issue issue1
Publisher Okayama University Medical School
Start Page 1
End Page 12
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2016 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26899604
Web of Science KeyUT 000371288700001
JaLCDOI 10.18926/AMO/55435
FullText URL 71_5_381.pdf
Author Yoshida, Kazuhiro| Umeda, Yuzo| Takaki, Akinobu| Nagasaka, Takeshi| Yoshida, Ryuichi| Nobuoka, Daisuke| Kuise, Takashi| Takagi, Kosei| Yasunaka, Tetsuya| Okada, Hiroyuki| Yagi, Takahito| Fujiwara, Toshiyoshi|
Abstract Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King’s College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines’ accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines’ criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.
Keywords living donor liver transplantation acute liver failure fulminant hepatic failure
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2017-10
Volume volume71
Issue issue5
Publisher Okayama University Medical School
Start Page 381
End Page 390
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2017 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 29042695
JaLCDOI 10.18926/AMO/60364
FullText URL 74_4_275.pdf
Author Muro, Taiko| Nakamura, Shinichiro| Takaki, Akinobu| Onishi, Hideki| Wada, Nozomu| Yasunaka, Tetsuya| Uchida, Daisuke| Oyama, Atsushi| Adachi, Takuya| Shiraha, Hidenori| Okada, Hiroyuki|
Abstract Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a promising method for controlling tumors, although it does not entirely eliminate recurrence. Oxidative stress is associated with the progression of hepatocarcinogenesis, while also acting as an anticancer response. The objective of the present study was to investigate the factors influencing post-RFA outcomes. We recruited 235 newly diagnosed HCC patients who received RFA for single tumors. The patients with recurrence were sub-grouped into early and segmental recurrence groups. The characteristics of the sub-grouped patients were evaluated, including by measuring oxidative stress marker reactive oxygen metabolites and antioxidant marker OXY-adsorbent tests. The factors associated with poor survival were a high Child-Pugh score and early recurrence within 2 years in the same segment. The patients who experienced recurrence within 2 years in the same segment showed a larger tumor diameter than did others. According to a multivariate analysis, the OXY values were also significantly low in these patients. In conclusion, maintaining the antioxidant reservoir function with a high OXY value might be necessary to prevent early recurrence within the RFA-treated segment.
Keywords oxidative stress hepatocellular carcinoma recurrence, radiofrequency ablation
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2020-08
Volume volume74
Issue issue4
Publisher Okayama University Medical School
Start Page 275
End Page 283
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2020 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 32843758
Web of Science KeyUT 000562508700002
NAID 120006880203
Author Takaki, Akinobu|
Published Date 1994-03-31
Publication Title
Content Type Thesis or Dissertation