研究者詳細 - 伊藤　隆徳

UTILITY OF THE ALBUMIN-BILIRUBIN SCORE FOR PREDICTING PROGNOSIS IN JAPANESE PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: AN ANALYSIS USING TIME-DEPENDENT RECEIVER OPERATING CHARACTERISTICS

Ito, T; Ishigami, M; Ishizu, Y; Kuzuya, T; Honda, T; Yasuda, S; Toyoda, H; Kumada, T; Fujishiro, M

HEPATOLOGY 70 巻頁： 789A - 790A 2019年10月

Clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment 査読有り

Kuzuya, T; Ishigami, M; Ito, T; Ishizu, Y; Honda, T; Ishikawa, T; Hirooka, Y; Fujishiro, M

HEPATOLOGY RESEARCH 49 巻 ( 9 ) 頁： 1054 - 1065 2019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：Hepatology Research

Aim: This study aimed to investigate the clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods: Of 122 patients, 103 were radiologically confirmed as progressive disease (PD) (sorafenib-refractory group), and 19 discontinued sorafenib therapy due to adverse events prior to radiologic PD (sorafenib-intolerant group). Patients in the sorafenib-refractory group were divided into two subgroups each, according to their eligibility for second-line treatment (second-line-in and -out group), regorafenib (RESORCE-in and -out group), or ramucirumab (REACH-2-in and -out group). Results: Patients included in the non-candidate group were those with α-fetoprotein level <400 ng/mL (n = 51, 49.5%), daily sorafenib dose <400 mg (n = 44, 42.7%), Child–Pugh B or C (n = 40, 38.8%), and Eastern Cooperative Oncology Group performance status score ≥2 (n = 24, 23.3%). The percentages of candidates were 57.3% for second-line, 35.0% for regorafenib, and 23.3% for ramucirumab. The median post-progression survival (PPS) was significantly longer for the second-line-in and the RESORCE-in groups than in the non-candidate groups (12.6 and 11.0 months vs. 3.0 and 6.1 months, respectively). The PPS was not significantly different between the REACH-2-in and -out groups. A significant predictor of candidates for second-line treatment at sorafenib initiation was a Child–Pugh score of 5 (A5). Conclusions: Not all patients refractory to sorafenib were candidates for second-line therapy. A Child–Pugh score of A5 at sorafenib initiation was an important and favorable factor related to eligibility for second-line therapy and good outcomes.

DOI： 10.1111/hepr.13358

The relationship between portal hypertension and the microbiome

Yamamoto, K; Honda, T; Hattori, S; Pu, LZCT; Ito, T; Yamamura, T; Ishizu, Y; Kuzuya, T; Ishigami, M; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 34 巻頁： 106 - 107 2019年9月

Association between core mutations and annual decline rate of HBVDNA and HBsAg in chronic hepatitis B patients treated with nucleoside analogue

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

JOURNAL OF HEPATOLOGY 70 巻 ( 1 ) 頁： E258 - E258 2019年4月

Association between gut microbiota and hepatocellular carcinoma in patients with chronic liver disease

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

JOURNAL OF HEPATOLOGY 70 巻 ( 1 ) 頁： E512 - E513 2019年4月

Serum Zinc levels as a prognostic factor for extra-hepatic carcinogenesis in Japanese patients with non-alcoholic liver disease

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

JOURNAL OF HEPATOLOGY 70 巻 ( 1 ) 頁： E298 - E298 2019年4月

The optimal cut-off points of FIB-4 index for predicting the incidences of HCC and extra-hepatic malignancies in biopsyproven Japanese NAFLD patients

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

JOURNAL OF HEPATOLOGY 70 巻 ( 1 ) 頁： E775 - E775 2019年4月

The early clinical response at 2 weeks of lenvatinib therapy for patients with advanced HCC

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

JOURNAL OF HEPATOLOGY 70 巻 ( 1 ) 頁： E611 - E611 2019年4月

Influence of proton pump inhibitors on microbiota in chronic liver disease patients 査読有り

Yamamoto, K; Ishigami, M; Honda, T; Takeyama, T; Ito, T; Ishizu, Y; Kuzuya, T; Hayashi, K; Goto, H; Hirooka, Y

HEPATOLOGY INTERNATIONAL 13 巻 ( 2 ) 頁： 234 - 244 2019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：Hepatology International

Background: Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease. Methods: From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child–Turcotte–Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states. Results: Before PSM, Child–Turcotte–Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different. Conclusions: Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.

DOI： 10.1007/s12072-019-09932-9

Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients 査読有り

Ito, T; Ishigami, M; Ishizu, Y; Kuzuya, T; Honda, T; Hayashi, K; Nishimura, D; Toyoda, H; Kumada, T; Goto, H; Hirooka, Y

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 34 巻 ( 1 ) 頁： 207 - 214 2019年1月

担当区分：筆頭著者記述言語：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 and Aim: The fibrosis stage of non-alcoholic fatty liver disease (NAFLD) is closely associated with long-term prognosis, including liver-related mortality. However, it is not yet clear whether noninvasive fibrosis markers can predict the incidence of non-liver-related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non-liver-related diseases, based on hepatic pathology and noninvasive fibrosis markers. Methods: A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers. Results: When these patients were categorized based on the severity of liver fibrosis as F0–2 (n = 196) and F3–4 (n = 50), the patients with F3–4 had significantly poorer prognosis in overall survival rates and all complications (P < 0.05). The fibrosis-4 (FIB-4) index was useful to predict overall survival and the incidence of hepatocellular carcinoma and liver cirrhosis (LC)-related complications but not extrahepatic malignancies. Multiple logistic regression analyses revealed the following risk factors: total bilirubin ≥ 1.2 (hazard ratio [HR] 6.362, 95% confidence interval [CI] 1.393–29.052) and severe liver fibrosis (HR 6.512, 95% CI 1.433–29.592) for overall survival; liver fibrosis (F3–4) (HR 13.370, 95% CI 2.775–64.427) for hepatocellular carcinoma; FIB-4 index (HR 26.560, 95% CI 3.320–212.494) for LC-related complications, and liver inflammation (A2–3) (HR 4.214, 95% CI 1.354–13.116) for extrahepatic malignancies. Conclusions: Severe liver fibrosis was associated not only with the hepatocarcinogenesis and LC-related complications but also with extrahepatic malignancies. The FIB-4 index was useful for predicting liver-related diseases but had limitations in predicting extrahepatic malignancies.

DOI： 10.1111/jgh.14448