研究者詳細 - 伊藤　隆徳

Simplification of balloon-occluded retrograde transcatheter obliteration procedure using a coaxial double balloon catheter compared with a single-balloon catheter.

Ishizu Y, Ishigami M, Honda T, Kuzuya T, Ito T, Komada T, Fujishiro M

Japanese journal of radiology 39 巻 ( 3 ) 頁： 296 - 302 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Radiology

Purpose: This study aimed to evaluate the usefulness of a coaxial double balloon catheter for simplification of the balloon-occluded retrograde transcatheter obliteration (BRTO) procedure compared with a single-balloon catheter. Materials and methods: Thirty-three patients who underwent BRTO with a single-balloon catheter (Single-balloon group, n = 15) or a coaxial double balloon catheter (Coaxial group, n = 18) were included, retrospectively. The frequency of additional procedures for stagnation of sclerosant including ethanol injection, coil embolization, and additional balloon occlusion for collateral draining veins; the dose of ethanolamine oleate (EO); and the complication rate and the success rate of sclerosant stagnation were evaluated. Results: Additional procedures were needed in four patients in the Coaxial group, which was significantly lower than that in the Single-balloon group (nine patients, P = 0.038). The dose of EO in the Coaxial group (11.2 ± 6.6 g) was lower, but not significantly different than that in the Single-balloon group (14.4 g ± 6.1 g, P = 0.184). The complication rate and the success rate of sclerosant stagnation were not different between the two groups. Conclusion: The use of a coaxial double balloon catheter can simplify the BRTO procedure compared with a single-balloon catheter.

DOI： 10.1007/s11604-020-01060-x

The relationship between oral-origin bacteria in the fecal microbiome and albumin-bilirubin grade in patients with hepatitis C.

Yamamoto K, Honda T, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Miyahara R, Kawashima H, Ishigami M, Fujishiro M

Journal of gastroenterology and hepatology 36 巻 ( 3 ) 頁： 790 - 799 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Gastroenterology and Hepatology Australia

Background: Bacteria of oral origin (BO) in the gut are associated with prognosis in patients with cirrhosis. The Greengenes database (gg_13_8) is widely used in microbiome analysis, but the expanded Human Oral Microbiome Database (eHOMD), a specialized database for BO, can add more detailed information. We used each database to evaluate the relationship between the albumin–bilirubin grade (ALBI) and the microbiome in patients with hepatitis C. Methods: Eighty patients were classified into the low ALBI group (LA; n = 34) or high ALBI group (HA; n = 46). Isolated DNA from stool was amplified to target the V3–4 regions of 16S rRNA. The microbiomes of the two groups were compared using gg_13_8 or eHOMD. We evaluated the associations between microbiomes and prognoses using Cox proportional hazards models. Results: At the genus level, the two groups differed significantly regarding 6 (gg_13_8) and 7 (eHOMD) types of bacteria. All types except Akkermansia are classified as BO. Both databases showed an increase in Streptococcus and Veillonella. eHOMD showed a decrease in Fusobacterium and an increase in Fretibacterium; both produce various types of short-chain fatty acids. At the species level, the two groups demonstrated significant differences in 2 (gg_13_8) and 6 (eHOMD) bacterial types. Selenomonas noxia and Streptococcus salivarius were related to poor prognosis in univariate analysis. Conclusion: The HA group demonstrated increased BO, most of which produce lactic acid or acetic acid. The correlation between the microbiome and metabolism might be related to prognosis. eHOMD was a useful database for analyzing BO.

DOI： 10.1111/jgh.15206

Progression After Molecular Targeted Agents: Hepatic Arterial Changes and Transarterial Chemoembolization in Hepatocellular Carcinoma. Open Access

Matsuda N, Imai N, Kuzuya T, Yamamoto K, Ito T, Ishizu Y, Honda T, Ishigami M, Fujishiro M

In vivo (Athens, Greece) 35 巻 ( 2 ) 頁： 1185 - 1189 2021年3月

Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia.

Yamamoto T, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M

Haemophilia : the official journal of the World Federation of Hemophilia 27 巻 ( 1 ) 頁： 100 - 107 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Haemophilia

Haemophilia is an X-linked inherited bleeding disorder caused by coagulation factor deficiency. Hepatocellular carcinoma (HCC) is a major complication associated with the disease. No study thus far has investigated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for HCC in patients with haemophilia. Aim: This study aimed to evaluate the safety and efficacy of RFA for HCC in haemophilia patients. Methods: From July 2008 to June 2019, 217 patients with HCC underwent 300 RFA sessions. Of these, 18 sessions were performed in ten haemophilia patients (H group) and 282 in 207 non-haemophilia patients (NH group). The patients' characteristics, incidence of haemorrhagic complications and rates of local tumour recurrence were compared between the groups. Results: A majority of the haemophilia patients received clotting factor concentrate replacement therapy before and after RFA treatment, with the aim of reaching a plasma clotting factor level of higher than 60%–80%. Twelve haemorrhagic complications were observed in the NH group (4.2%; 12/282). Major bleeding requiring control procedures was observed in two patients and minor bleeding with careful observation was noted in ten patients. No bleeding complications were observed in the H group (0/18). There were no significant differences in the 5-year local tumour recurrence rates after RFA treatment between the groups (35.0% in the H group and 32.1% in the NH group). Conclusion: RFA could be an effective and a safe method for HCC treatment in patients with haemophilia.

DOI： 10.1111/hae.14220

Increased Frequency of Dysfunctional Siglec-7(-)CD57(+)PD-1(+) Natural Killer Cells in Patients With Non-alcoholic Fatty Liver Disease. Open Access

Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure. Open Access

Honda T, Yamada N, Murayama A, Shiina M, Aly HH, Kato A, Ito T, Ishizu Y, Kuzuya T, Ishigami M, Murakami Y, Tanaka T, Moriishi K, Nishitsuji H, Shimotohno K, Ishikawa T, Fujishiro M, Muramatsu M, Wakita T, Kato T

Cellular and molecular gastroenterology and hepatology 12 巻 ( 5 ) 頁： 1583 - 1598 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cellular and Molecular Gastroenterology and Hepatology

Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.

DOI： 10.1016/j.jcmgh.2021.07.013

Sakamoto Y, Yoshio S, Doi H, Mori T, Matsuda M, Kawai H, Shimagaki T, Yoshikawa S, Aoki Y, Osawa Y, Yoshida Y, Arai T, Itokawa N, Atsukawa M, Ito T, Honda T, Mise Y, Ono Y, Takahashi Y, Saiura A, Taketomi A, Kanto T

Frontiers in immunology 12 巻頁： 603133 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Immunology

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that can develop into liver fibrosis and hepatocellular carcinoma. Natural killer (NK) cells have been shown to protect against liver fibrosis and tumorigenesis, suggesting that they may also play a role in the pathogenesis of NAFLD. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of inhibitory and activating receptors expressed by many cell types, including NK cells. Here, we investigated the phenotypic profiles of peripheral blood and intrahepatic NK cells, including expression of Siglecs and immune checkpoint molecules, and their association with NK cell function in patients with NAFLD. Immune cells in the peripheral blood of 42 patients with biopsy-proven NAFLD and 13 healthy volunteers (HVs) were identified by mass cytometry. The function of various NK cell subpopulations was assessed by flow cytometric detection of intracellular IFN-γ and CD107a/LAMP-1, a degranulation marker, after in vitro stimulation. We found that peripheral blood from NAFLD patients, regardless of fibrosis stage, contained significantly fewer total CD56+ NK cell and CD56dim NK cell populations compared with HVs, and the CD56dim cells from NAFLD patients were functionally impaired. Among the Siglecs examined, NK cells predominantly expressed Siglec-7 and Siglec-9, and both the expression levels of Siglec-7 and Siglec-9 on NK cells and the frequencies of Siglec-7+CD56dim NK cells were reduced in NAFLD patients. Notably, Siglec-7 levels on CD56dim NK cells were inversely correlated with PD-1, CD57, and ILT2 levels and positively correlated with NKp30 and NKp46 levels. Further subtyping of NK cells identified a highly dysfunctional Siglec-7−CD57+PD-1+CD56dim NK cell subset that was increased in patients with NAFLD, even those with mild liver fibrosis. Intrahepatic NK cells from NAFLD patients expressed elevated levels of NKG2D and CD69, suggesting a more activated phenotype than normal liver NK cells. These data identify a close association between NK cell function and expression of Siglec-7, CD57, and PD-1 that could potentially be therapeutically targeted in NAFLD.

DOI： 10.3389/fimmu.2021.603133

SAFETY AND EFFICACY OF PERCUTANEOUS RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA PATIENTS WITH HEMOPHILIA

Yamamoto, T; Ishigami, M; Yamamoto, K; Ito, T; Imai, N; Lshizu, Y; Honda, T; Fujishiro, M

HEPATOLOGY 72 巻頁： 705A - 706A 2020年11月

GUT MICROBIOTA ASSOCIATED WITH THE DIFFERENCE BETWEEN PATIENTS WITH AND WITHOUT HEPATOCELLULAR CARCINOMA IN CHRONIC LIVER DISEASE

Honda, T; Ishigami, M; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Fujishiro, M

HEPATOLOGY 72 巻頁： 370A - 370A 2020年11月

IMPROVEMENT OF LIVER FUNCTIONAL RESERVE AFTER SVR IN HCV-PATIENTS WITH COMPENSATED, SEVERE FIBROSIS BY IFN-FREE, DAA COMBINATION TREATMENT-IMPACT OF PRETREATMENT SERUM AFP LEVELS

Ishigami, M; Honda, T; Ishizu, Y; Imai, N; Ito, T; Yamamoto, K; Fujishiro, M

HEPATOLOGY 72 巻頁： 564A - 565A 2020年11月

AMINO ACID POLYMORPHISM IN HEPATITIS B VIRUS ASSOCIATED WITH NATURAL CLEARANCE OF HBV DNA AND HBsAg

Honda, T; Yamada, N; Murayama, A; Kato, A; Ito, T; Ishizu, Y; Kuzuya, T; Ishigami, M; Murakami, Y; Ishikawa, T; Fujishiro, M; Kato, T

HEPATOLOGY 72 巻頁： 508A - 509A 2020年11月

THE EPIDEMIOLOGY OF NAFLD AND LEAN NAFLD IN JAPAN: A SYSTEMATIC REVIEW AND META-ANALYSIS WITH INDIVIDUAL PATIENT LEVEL DATA AND FORECASTING, 1995-2040

Ito, T; Ishigami, M; Zou, BY; Tanaka, T; Takahashi, H; Kurosaki, M; Maeda, M; Thin, KN; Tanaka, K; Takahashi, Y; Itoh, Y; Oniki, K; Seko, Y; Saruwatari, J; Kawanaka, M; Atsukawa, M; Hyogo, H; Ono, M; Ogawa, E; Barnette, SD; Stave, CD; Cheung, R; Fujishiro, M; Eguchi, Y; Toyoda, H; Nguyen, MH

HEPATOLOGY 72 巻頁： 999 - 999 2020年11月

The albumin-bilirubin score as a predictor of outcomes in Japanese patients with PBC: an analysis using time-dependent ROC. Open Access

Ito T, Ishigami M, Morooka H, Yamamoto K, Imai N, Ishizu Y, Honda T, Nishimura D, Tada T, Yasuda S, Toyoda H, Kumada T, Fujishiro M

Scientific reports 10 巻 ( 1 ) 頁： 17812 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

The albumin–bilirubin (ALBI) score is calculated using only serum albumin and bilirubin levels, and was developed as a simple method to assess hepatic function. In this study, a total of 409 patients with primary biliary cholangitis (PBC) were enrolled between March 1990 and October 2018. The predictive performances of the ALBI score and other well-established prognostic scores were compared using time-dependent receiver operating characteristic (ROC) analysis. During the follow-up period, 60 patients died, 45 due to liver-related diseases and 15 due to non-liver-related diseases, and 16 patients underwent liver transplantation. Time-dependent ROC analysis showed that the ALBI score has higher the areas under the ROC curves (AUROCs) than the Child–Pugh (C–P) score at each time point; AUROCs at 3, 5, and 10 years after the start of follow-up were 0.94, 0.91, and 0.90 for the ALBI score, and 0.89, 0.88, and 0.82 for the C–P score, respectively. The ALBI score showed the highest AUROCs within 2 years after the start of observation; beyond 2 years, however, the Mayo score had better prognostic ability for mortality and liver transplantation. The ALBI score/grade, derived from objective blood tests, and the Mayo score were superior prognostic tools in PBC patients.

DOI： 10.1038/s41598-020-74732-3

Revisiting the indications for liver transplantation in cirrhotic patients considering the long-term outcomes of cirrhotic patients.

Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Kamei H, Ogura Y, Fujishiro M

Journal of hepato-biliary-pancreatic sciences 27 巻 ( 9 ) 頁： 655 - 662 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Hepato Biliary Pancreatic Sciences

Background: In this study, we investigated long-term survival of cirrhotic patients without hepatocellular carcinoma (HCC) and the proper timing of liver transplantation in the era with recent progress of management. Methods: We first classified 217 non-transplant cirrhotic patients without HCC according to the long-term survival based on Child-Turcotte-Pugh (CTP) scores and the MELD scores. We then compared them with the survival after liver transplantation in 114 patients with liver cirrhosis. Results: We classified into four groups (class A as CTP score of 5,6, B as 7,8, C as 9-12, D as 13-15) according to the long-term survival of the patients, the survivals of patients with class C and D were significantly worse compared with transplant patients (P < 0.001 in each group). And we also classified into four groups based on the MELD scores (class A as MELD score of −8, B as 9-12, C as 13-19, D as 19-), the survivals of patients with class C and D were significantly worse compared with those of transplant patients (P < 0.001 in each group). Conclusions: Considering the long-term survival of patients with liver cirrhosis, CTP score of 9 and/or MELD score of 13 could be a proper timing for liver transplantation.

DOI： 10.1002/jhbp.777