研究者詳細 - 伊藤　隆徳

論文 - 伊藤　隆徳

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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 査読有り

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

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：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 査読有り

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

Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion 査読有り

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

ONCOLOGY 98 巻 ( 9 ) 頁： 621 - 629 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：Oncology (Switzerland)

Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. Methods: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. Results: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. Conclusions: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.

DOI： 10.1159/000507051

Editorial: impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis-a prospective serial follow-up MRI study 査読有り

Ito, T

ALIMENTARY PHARMACOLOGY & THERAPEUTICS 52 巻 ( 4 ) 頁： 735 - 736 2020年8月

Limitation of non-transplant treatment and proper timing for liver transplantation in patients with hepatocellular carcinoma considering long-term survival 査読有り

Nomura, A; Ishigami, M; Honda, T; Kuzuya, T; Ishizu, Y; Ito, T; Kamei, H; Onishi, Y; Ogura, Y; Fujishiro, M

MEDICINE 99 巻 ( 28 ) 頁： e21161 2020年7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：Medicine (United States)

In this study, we investigated the long-term survival of patients with hepatocellular carcinoma (HCC) after conventional treatment other than liver transplantation (LT) in our institute and discuss the limitation of non-transplant treatment for HCC and the proper indictors of LT in the recent comprehensive era. Between 2003 and 2016, 181 patients with HCC aged ≤70 years received active treatment including liver resection, radiofrequency ablation (RFA), and transcatheter arterial chemoembolization (TACE). We analyzed the factors associated with overall survival and proposed new priority for the indicators of LT in HCC patients according to the extracted factors by comparing the survival with 39 transplanted patients with HCC. Child-Turcotte-Pugh (CTP) score (HR: 1.276; 95% CI: 1.049-1.552, P=.015), and number of tumors (HR: 1.238; 95% CI: 1.112- 1.377, P<.001) were selected as significant factors associated with the survival after active treatments for HCC. Patients with LT had significantly better long-term survival compared with those with non-transplant patients regardless of aforementioned factors. However, regarding relatively short survival (3 years), patients with CTP score of ≥9and/or ≥3 tumors with non-transplant treatment had poorer survival compared with those of transplanted patients (P<.05). We propose that CTP score of 9 and/or 3 tumors before non-transplant, intensive treatment might be a new priority for considering indicators of LT in patients with HCC. Abbreviations: AASLD = American Association of Liver Disease, AFP = serum alphafetoproetein, APASL = Asian Pacific Association for the Study of Liver diseases, BCLC = Barcelona Clinic Liver Cancer, CTP = Child-Turcotte-Pugh, DCP = des-gamma carboxy prothrombin, EASL = European Association for the Study of Liver, EORTC = European Organisation for Research and Treatment of Cancer, HCC = hepatocellular carcinoma, HCV = Hepatitis C virus, JSH = Japanese Society of Hepatology, LT = liver transplantation, MELD = model of end-stage liver disease, NCCN = National Comprehensive Cancer Network, PIVKA-II = protein induced by vitamin K absence or antagonists II, RFA = radiofrequency ablation, TACE = transcatheter arterial chemoembolization.

DOI： 10.1097/MD.0000000000021161

Serum Nutritional Markers as Prognostic Factors for Hepatic and Extrahepatic Carcinogenesis in Japanese Patients with Nonalcoholic Fatty Liver Disease 査読有り

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

NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 72 巻 ( 5 ) 頁： 884 - 891 2020年7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：Nutrition and Cancer

Serum zinc (Zn) levels and the branched chain amino acid/tyrosine molar ratio (BTR) were reported to decrease with the progression of various chronic liver diseases. We investigated the impact of BTR and Zn on the incidence of malignancies in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). A total of 179 Japanese NAFLD patients who underwent liver biopsy were enrolled. Hepatocellular carcinoma (HCC) and extrahepatic malignancies developed in 7 (3.9%) and 10 (5.6%) patients, respectively, during the follow-up period (median 7.9 years). Patients with low BTR levels (<5.0) and Zn deficiency (<70 μg/dL) had significantly higher incidences of HCC and extrahepatic malignancies (P < 0.001 and 0.026), respectively. Multiple logistic regression analyses revealed the following risk factors: liver fibrosis (F3–4) (hazard ratio [HR] 24.292, 95% confidence interval [CI] 2.802–210.621, P = 0.004) and BTR < 5.0 (HR 5.462, 95% CI 1.095–27.253, P = 0.038) for HCC, and serum Zn level <70 μg/dL (HR 3.504, 95% CI 1.010–12.157, P = 0.048) and liver inflammation (A2–3) (HR 3.445, 95% CI 0.886–13.395, P = 0.074) for extra-hepatic malignancies. In conclusion, serum BTR and Zn levels were useful for predicting HCC and extrahepatic malignancies in NAFLD, respectively.

DOI： 10.1080/01635581.2019.1653474

特集薬剤性消化器疾患の診療 4 .その他の薬剤性消化器疾患(4)免疫チェックポイント阻害薬による消化器障害

伊藤隆徳, 澤田つな騎, 中村正直, 本多隆, 石上雅敏, 藤城光弘

臨床消化器内科 35 巻 ( 7 ) 頁： 759 - 765 2020年6月

Complete response of advanced hepatocellular carcinoma achieved by sorafenib dose re-escalation after failure of long-term low-dose-sorafenib treatment combined with transcatheter arterial chemoembolization: a case report 査読有り

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

CLINICAL JOURNAL OF GASTROENTEROLOGY 13 巻 ( 3 ) 頁： 397 - 402 2020年6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：Clinical Journal of Gastroenterology

Few reports have described dose re-escalation after long-term low-dose sorafenib leading to good outcomes. Here, we report the case of an 80-year-old woman with advanced hepatocellular carcinoma who achieved complete response from sorafenib dose re-escalation after the failure of long-term low-dose sorafenib treatment combined with transcatheter arterial chemoembolization. Sorafenib therapy was initiated at 400 mg once daily due to old age and low platelet count. 5 months later, this dose was reduced to 200 mg once daily because of adverse events. Best radiological antitumor response by sorafenib treatment alone was judged as stable disease according to the modified Response Evaluation Criteria in Solid Tumors. 1 year later, she showed progressive disease owing to the progression of intrahepatic lesions. She received combination therapy with low-dose sorafenib (200 mg every other day) and transcatheter arterial chemoembolization, which proved relatively effective for three and a half years. Antitumor response by the fourth transcatheter arterial chemoembolization and subsequent low-dose sorafenib was clearly progressive disease. At that time, sorafenib-related adverse events were well-controlled. Sorafenib dose was re-escalated to 200 mg once daily. After this re-escalation, tumor markers declined rapidly, and adverse events remained tolerable. 4 months later, complete response was achieved.

DOI： 10.1007/s12328-019-01066-7

Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease 査読有り

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

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY 32 巻 ( 6 ) 頁： 748 - 753 2020年6月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：European Journal of Gastroenterology and Hepatology

Objective Chronic liver diseases are associated with zinc (Zn) deficiency. However, no previous studies have examined the relationship between serum Zn levels and hepatic pathological findings in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the serum Zn levels in NAFLD patients based on pathological/laboratory findings. Methods We evaluated a total of 191 NAFLD patients who underwent liver biopsy with the goal of identifying laboratory markers and pathological findings associated with serum Zn levels. Results Zn levels significantly decreased along with progression of hepatic fibrosis (P=0.039), but there were no significant differences among inflammatory grades. Zn levels were most strongly correlated with albumin levels (r=0.410, P<0.001). In addition, Zn levels were significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r=−0.284, P<0.001), hyaluronic acid (r=−0.230, P<0.001), branched chain amino acid/tyrosine molar ratio (BTR) (r=0.278, P<0.001), FIB-4 index (r=−0.238, P<0.001), and NAFLD fibrosis score (NFS) (r=−0.261, P<0.001). In multivariate analysis, albumin [odds ratio (OR), 9.244 (per 1g/dL decrease) [95% confidence interval (CI), 2.261–32.744]; P<0.001], BTR [OR, 1.545 (per 1 decrease) (95% CI, 1.115–2.140); P=0.009], and HOMA-IR [OR, 1.048 (per 1 increase) (95% CI, 1.019–1.167); P=0.028] were significantly associated with Zn deficiency. Conclusion The progression of liver fibrosis, but not inflammation, is associated with lower serum Zn levels in biopsy-proven NAFLD patients. Serum Zn levels were correlated with nutrition markers and insulin resistance.

DOI： 10.1097/MEG.0000000000001587

Initial Experience of Ramucirumab Treatment After Lenvatinib Failure for Patients With Advanced Hepatocellular Carcinoma 査読有り

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

ANTICANCER RESEARCH 40 巻 ( 4 ) 頁： 2089 - 2093 2020年4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：Anticancer Research

Background/Aim: The outcomes of ramucirumab after lenvatinib failure for hepatocellular carcinoma (HCC) patients with alpha fetoprotein (AFP) levels of ≥400 ng/ml are unknown. Patients and Methods: Of 12 patients treated with ramucirumab after lenvatinib failure, 10 patients were enrolled in this retrospective study. Results: The disease control rate of 80% at 6 weeks and the median time to progression of 3.1 months were the same by both the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified RECIST. AFP reduction was seen in 5 patients at 2 weeks and in 3 patients at 6 weeks. The incidence of grade 3 adverse events was low at 10%. The albumin.bilirubin scores within 6 weeks did not worsen. Conclusion: Ramucirumab might have potential therapeutic efficacy and safety in advanced HCC patients after lenvatinib failure. Further studies are needed to confirm the outcomes of ramucirumab after lenvatinib failure.

DOI： 10.21873/anticanres.14167

Serum soluble sialic acid-binding immunoglobulin-like lectin-7 concentration as an indicator of liver macrophage activation and advanced fibrosis in patients with non-alcoholic fatty liver disease 査読有り

Sakamoto, Y; Yoshio, S; Doi, H; Kawai, H; Shimagaki, T; Mori, T; Matsuda, M; Aoki, Y; Osawa, Y; Yoshida, Y; Arai, T; Itokawa, N; Ito, T; Seko, Y; Yamaguchi, K; Itoh, Y; Mise, Y; Saiura, A; Taketomi, A; Kanto, T

HEPATOLOGY RESEARCH 50 巻 ( 4 ) 頁： 466 - 477 2020年4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: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Because liver fibrosis is associated with the long-term prognosis of patients with NAFLD, there is an urgent need for non-invasive markers of liver fibrosis. Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an immunomodulatory molecule expressed on various immune cells, including macrophages, which plays a key role in liver inflammation and fibrosis in NAFLD. We aimed to determine whether serum levels of soluble Siglec-7 (sSiglec-7) could have utility at a marker of fibrosis in this patient population. Methods: We examined serum samples from 93 NAFLD patients and 19 healthy donors for macrophage-associated protein, including sSiglec-7, soluble CD163, and YKL-40, and examined their correlation with liver fibrosis scores, tissue elastography, and histological findings. Independent factors associated with advanced fibrosis were analyzed using a logistic regression model and a decision tree. To clarify the source of sSiglec-7, we examined its expression in liver tissue-derived macrophages and cultured monocyte-derived macrophages. Results: Serum sSiglec-7 levels were significantly higher in NAFLD patients compared with healthy donors, and correlated positively with sCD163 and YKL-40 levels. Serum sSiglec-7 was an independent diagnostic marker with high specificity (96.3%) for advanced fibrosis (F3 and F4) in NAFLD patients. Siglec-7 was mainly expressed on CCR2+ macrophages in the liver, and sSiglec-7 production by monocyte-derived macrophages in vitro was increased after stimulation by pro-inflammatory factors. Conclusions: Elevated serum sSiglec-7 could serve as an independent marker with high specificity for advanced liver fibrosis in patients with NAFLD.

DOI： 10.1111/hepr.13464

Sorafenib <i>vs</i>. Lenvatinib as First-line Therapy for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis 査読有り

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

ANTICANCER RESEARCH 40 巻 ( 4 ) 頁： 2283 - 2290 2020年4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：Anticancer Research

Background/Aim: We aimed to compare the outcomes between sorafenib and lenvatinib as first-line therapy for advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (Vp3/4). Patients and Methods: This retrospective study enrolled 41 HCC patients with Vp3/4 and Child-Pugh A. Results: The outcomes in the lenvatinib group (n=13) were significantly better than those in the sorafenib group (n=28) [best objective response rate according to the modified Response Evaluation Criteria in Solid Tumors: 53.8% vs. 14.3%; p=0.0193, best disease control rate: 92.3% vs. 35.7%; p=0.0008, median overall survival (OS): not reached vs. 187 days; p=0.0040, respectively]. Lenvatinib treatment was the only significant predictor of better OS and time to tumor progression. No patient needed to discontinue lenvatinib treatment due to drug-related adverse events. Conclusion: Compared with sorafenib, lenvatinib treatment for advanced HCC with Vp3/4 may lead to more favorable outcomes.

DOI： 10.21873/anticanres.14193

Dynamic Evaluation of Liver Fibrosis to Assess the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Who Achieved Sustained Virologic Response. 査読有り

Toyoda H, Tada T, Yasuda S, Mizuno K, Ito T, Kumada T

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 70 巻 ( 6 ) 頁： 1208 - 1214 2020年3月

Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma 査読有り

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

HEPATOLOGY RESEARCH 50 巻 ( 3 ) 頁： 374 - 381 2020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 Research

Aim: We aimed to investigate the radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma in real-world practice. Methods: This retrospective study enrolled 40 patients who received lenvatinib. Radiological antitumor response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Results: The objective response rate at 2 weeks and best overall response on confirmation of complete response, partial response (PR), and stable disease required (confirmed response) were 57.5% and 32.5%, respectively. Based on confirmed response, the overall survival rate was significantly longer in patients with an objective response rate than in those with stable disease or progressive disease after 12 months (73.2% and 54.2%, P = 0.0358). All 13 patients with an objective response rate on confirmed response were evaluated as PR at 2 weeks. The alpha-fetoprotein ratio at 2 weeks was a significant factor associated with PR of response rate at 2 weeks. The median relative dose intensity from 2 to 6 weeks was significantly lower than that from 0 to 2 weeks (69.6% vs. 100%, P < 0.0001). Stratified by the antitumor response at 6 weeks considering the image evaluation at 2 weeks, the median relative dose intensity from 2 to 6 weeks was significantly lower in patients with progressive disease than in those with PR or stable disease (45.2% vs. 72.6%, P = 0.0482). Conclusions: The radiological antitumor response at 2 weeks was favorable. Information on a favorable visible therapeutic response very early after lenvatinib initiation can help patients maintain their motivation for treatment, and allow physicians to continue treatment effectively and safely.

DOI： 10.1111/hepr.13452

Relationship Between Adverse Events and Microbiomes in Advanced Hepatocellular Carcinoma Patients Treated With Sorafenib 査読有り

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

ANTICANCER RESEARCH 40 巻 ( 2 ) 頁： 665 - 676 2020年2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：Anticancer Research

Background/Aim: Sorafenib results in several adverse events, the mechanism and predictors of which are unknown. Recently, it was reported that metabolism by microbiome changes the structure and effects of drugs. The blood levels of sorafenib may be affected by enterohepatic recycling of sorafenib due to microbial enzymes in the gut. We evaluated the relationship between adverse events caused by sorafenib treatment and microbiome in patients with advanced hepatocellular carcinoma. Materials and Methods: Twenty-five patients were classified into two groups based on the presence of hand-foot syndrome (HFS) or diarrhea within 12 weeks post-sorafenib treatment. Before sorafenib treatment, the fecal samples were analyzed targeting the V3- V4 region of 16s ribosomal RNA. Microbiome and predicted functional gene were compared between two groups. Results: The non-HFS group had a richer abundance of Veillonella, Bacillus, Enterobacter, Faecalibacterium, Lachnospira, Dialister, and Anaerostipes than the HFS group at genus level. Carotenoid biosynthesis and bacterial invasion of epithelial cells were enriched in the HFS group. The former three bacteria are classified as oral-origin bacteria, and the two predicted functions are associated with dysbiosis. The non-diarrhea group had a higher abundance of Butyricimonas and a lower abundance of Citrobacter, Peptostreptococcus, and Staphylococcaceae than the diarrhea group. Eight categories of predicted functional genes were detected with differences between the two groups. Conclusion: The non-HFS group had a higher relative abundance of oral-origin bacteria, which likely led to more robust dysbiosis in the gut. This dysbiosis may affect enterohepatic recycling. Additionally, the metabolism of these short-chain fatty acids in the gut may be different between the diarrhea and non-diarrhea groups.

DOI： 10.21873/anticanres.13996

Effect of weight change and lifestyle modifications on the development or remission of nonalcoholic fatty liver disease: sex-specific analysis 査読有り

Yoshioka, N; Ishigami, M; Watanabe, Y; Sumi, H; Doisaki, M; Yamaguchi, T; Ito, T; Ishizu, Y; Kuzuya, T; Honda, T; Ishikawa, T; Haruta, J; Fujishiro, M

SCIENTIFIC REPORTS 10 巻 ( 1 ) 頁： 481 2020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：Scientific Reports

The effects of changes in various lifestyle habits on nonalcoholic fatty liver disease (NAFLD) have not been well elucidated. We aimed to clarify how weight change and lifestyle modifications were associated with the development or remission of NAFLD. In this longitudinal cohort study, we reviewed the periodic health checkup data of 1,421 subjects with no causes of liver disease besides NAFLD who had received at least two health checkups between 2009 and 2018. The prevalence of NAFLD at baseline was 34.1% (484/1,421). During follow-up period (4.6 ± 2.8 years), 104 subjects developed NAFLD and 127 subjects demonstrated NAFLD remission. The frequency of NAFLD development or that of NAFLD remission significantly increased as the larger weight gain or weight loss was, respectively (both, p < 0.001). Approximately 40% of the subjects who maintained ≥ 1%/year weight loss achieved NAFLD remission. By multivariate analysis, quitting smoking were independently associated with NAFLD development (adjusted odds ratio [AOR], 2.86; 95% CI, 1.24–6.62). Subjects who quit smoking demonstrated large weight gain (≥1%/year) significantly more frequently than the other subjects (p < 0.001). In sex-specific analysis, starting to exercise was independently associated with NAFLD remission in men (AOR, 2.38; 95% CI, 1.25–4.53).

DOI： 10.1038/s41598-019-57369-9

Rapid increase of platelet counts during antiviral therapy in patients with hepatitis C virus infection 査読有り

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

HEPATOLOGY RESEARCH 50 巻 ( 1 ) 頁： 47 - 56 2020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：Hepatology Research

Aim: The cause of thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is multifactorial: hypersplenism, decreased thrombopoietin levels, and myelosuppression induced by HCV. Platelet counts increase after eradication of HCV; however, this mechanism is not fully understood. Therefore, the aim of this study was to determine the influence of these three factors on platelet counts. Methods: We retrospectively analyzed data from 109 HCV-infected patients with platelet counts ≤150 × 103/μL who achieved viral eradication using interferon-free anti-HCV therapy. Changes in hematological parameters, thrombopoietin levels, HCV titers, and spleen volumes, and the correlations among them were evaluated. Results: HCV RNA levels significantly decreased at 4 weeks after initiating antiviral therapy. Platelet counts rapidly increased at 4 weeks from baseline (120 ± 35 vs. 106 ± 28 × 103/μL, P < 0.001), and remained at a plateau until 48 weeks after initiating antiviral therapy. Neutrophil counts showed the same pattern. Spleen volume was evaluated in 32 patients and, among them, it decreased in 21 patients, but remained unchanged in seven and increased in four. In addition to patients with decreased spleen volume, patients with unchanged spleen volume showed marginally increased platelet counts. Thrombopoietin levels did not correlate with platelet counts. Conclusions: Platelet counts increased at 4 weeks after starting anti-HCV treatment. Our results suggest that this rapid change was possibly caused by improvement of hypersplenism and HCV-induced myelosuppression resulting from anti-HCV therapy.

DOI： 10.1111/hepr.13426

Sarcopenia impairs health-related quality of life in cirrhotic patients 査読有り

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

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY 31 巻 ( 12 ) 頁： 1550 - 1556 2019年12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：European Journal of Gastroenterology and Hepatology

Aim Sarcopenia is associated with poor health-related quality of life (HRQOL) in the general population. However, in cirrhotic patients, as the development of sarcopenia is closely related to declined liver function, which also impairs HRQOL, whether sarcopenia deteriorates HRQOL independently from declined liver function remains unclear. The aim of this study was to clarify the impact of sarcopenia on HRQOL impairment in cirrhotic patients. Patients and methods A total of 88 cirrhotic patients [median age, 69 years; range: 31-79 years; 49 male (55.7%), 45 with hepatocellular carcinoma (51.1%)] were analyzed. We measured HRQOL using the 36-item Short-Form Health Survey version 2 questionnaire and identified factors contributing to scores lower than 50 in physical component summary (PCS), mental component summary, and role-social component summary (RCS) scores. Results Twenty-four (27.2%) patients had sarcopenia. PCS and RCS scores were significantly lower in patients with sarcopenia compared with those without sarcopenia. Patients with Child-Pugh (CP) classification B or C showed significantly lower scores in PCS and RCS than those with CP classification A. On multivariate analysis, the presence of sarcopenia was the only factor associated with low PCS scores [odds ratio (OR): 11.6; P = 0.031]. Female sex (OR: 3.34; P = 0.034), CP classification B or C (OR: 3.19; P = 0.037), and presence of sarcopenia (OR: 4.64; P = 0.016) were identified as independent factors for low RCS scores. Conclusion Sarcopenia independently impairs physical and role-social HRQOL in cirrhotic patients.

DOI： 10.1097/MEG.0000000000001472

CHANGES OF MICROBIOTA AFTER HEPATITIS C VIRUS ERADICATION

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

HEPATOLOGY 70 巻頁： 1160A - 1161A 2019年10月

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