研究者詳細 - 伊藤　隆徳

論文 - 伊藤　隆徳

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Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies.

Mizuno K, Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Kawashima H, Inukai Y, Toyoda H, Yokota K, Hase T, Maeda O, Kiyoi H, Nagino M, Hibi H, Kodera Y, Fujimoto Y, Sone M, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Fujishiro M

Journal of gastroenterology 55 巻 ( 6 ) 頁： 653 - 661 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：Journal of Gastroenterology

Background: Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. Methods: A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. Results: Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65–10.80, P = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68–14.40, P < 0.001). Conclusions: We found that the use of ipilimumab and the presence of fever within 24 h of initial ICI administration were predictive factors for immune-related liver injury.

DOI： 10.1007/s00535-020-01677-9

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

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

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. Open Access

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.

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 : the official journal of the Japan Society of Hepatology 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<sup>+</sup> 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 vs. Lenvatinib as First-line Therapy for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis. Open Access

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.

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

Hepatology research : the official journal of the Japan Society of Hepatology 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. Open Access

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. Open Access

Yoshioka N, Ishigami M, Watanabe Y, Sumi H, Doisaki M, Yamaguchi T, Ito T, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Haruta JI, 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.

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

Hepatology research : the official journal of the Japan Society of Hepatology 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 × 10<sup>3</sup>/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 × 10<sup>3</sup>/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

Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

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

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

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

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

Nutrition and cancer 72 巻 ( 5 ) 頁： 884 - 891 2020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：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

反復的な内視鏡的静脈瘤硬化療法により食道胃静脈瘤の退縮が得られた乳児胆道閉鎖症の１例

横山晋也, 本多隆, 葛谷貞二, 石津洋二, 伊藤隆徳, 山本健太, 田中卓, 武藤久哲, 杉山由晃, 藤城光弘

日本消化器内視鏡学会雑誌 62 巻 ( 12 ) 頁： 3064 - 3071 2020年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本消化器内視鏡学会

<p>症例は10カ月男児，胆道閉鎖症にて葛西手術後経過観察中に下血を認め，緊急内視鏡を施行した．食道静脈瘤からの出血を認めたため内視鏡的静脈瘤結紮術（EVL）を試みたが，食道入口部が狭いためにEVLデバイスが通過せず，内視鏡的静脈瘤硬化療法（EIS）により止血を得た．その後，残存した静脈瘤に対し反復的に血管内外EISを施行した．血管外EIS後に食道潰瘍に伴う浮腫性狭窄が生じ，経口摂取不良を認めた．経腸栄養剤による栄養療法の併用を要したが保存的に軽快し，最終的に静脈瘤の退縮が得られた．乳幼児の食道胃静脈瘤に対する血管内外EISは有効な治療法であるが，術後の狭窄には十分に注意する必要がある．</p>

DOI： 10.11280/gee.62.3064

Sarcopenia impairs health-related quality of life in cirrhotic patients.

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

Successful Treatment of Hepatocellular Carcinoma with Regorafenib after Sorafenib-induced Hypersensitivity. Open Access

Yoshioka N, Kuzuya T, Ito T, Ishizu Y, Honda T, Ishikawa T, Ishigami M, Fujishiro M

Internal medicine (Tokyo, Japan) 58 巻 ( 19 ) 頁： 2803 - 2808 2019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：一般社団法人日本内科学会

Sorafenib and regorafenib are tyrosine kinase inhibitors that are used in the treatment of hepatocellular carcinoma and which have similar chemical structures and toxicity profiles. We herein report a case in which regorafenib treatment could be continued for 10 months and stable disease could be maintained for a long period despite the discontinuation of sorafenib due to grade 4 liver injury and grade 3 fever. The severe adverse events could be attributed to drug hypersensitivity, since a drug-induced lymphocyte stimulation test (DLST) indicated sensitivity to sorafenib. A DLST for regorafenib was negative. This is the first report showing that regorafenib could be safely administered after the discontinuation of sorafenib due to hypersensitivity.

DOI： 10.2169/internalmedicine.2812-19

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

NON-INVASIVE SCREENING FOR DETECTING ESOPHAGOGASTRIC VARICES IN CHILDREN WITH BILIARY ATRESIA

Yokoyama, S; Ishigami, M; Honda, T; Kuzuya, T; Ishizu, Y; Ito, T; Shirota, C; Uchida, H; Fujishiro, M

HEPATOLOGY 70 巻頁： 200A - 200A 2019年10月

INDICATION FOR HCC TREATMENT IN RECENT ERA-PROPOSAL OF THE NEW PRIORITY FOR LIVER TRANSPLANTATION IN PATIENTS WITH HCC

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

HEPATOLOGY 70 巻頁： 543A - 544A 2019年10月

Spleen stiffness by 2-D shear wave elastography is the most accurate predictor of high-risk esophagogastric varices in children with biliary atresia.

Yokoyama S, Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Hirooka Y, Tanaka Y, Tainaka T, Shirota C, Chiba K, Uchida H, Fujishiro M

Hepatology research : the official journal of the Japan Society of Hepatology 49 巻 ( 10 ) 頁： 1162 - 1168 2019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：Hepatology Research

Aim: Esophagogastric variceal hemorrhage is a cause of poor prognosis in patients with biliary atresia (BA). To prevent variceal hemorrhage, simple and reliable screening methods for high-risk esophagogastric varices (HR-EGV) are needed. We evaluated the efficacy of liver stiffness (LS) and spleen stiffness (SS) as measured by 2-D shear wave elastography (2D-SWE), which was reported to be more accurate than transient elastography, for detecting HR-EGV in children with BA. Methods: Thirty-four children with BA were enrolled. Both LS and SS were measured by 2D-SWE. The presence of large esophageal varices or esophageal varices of any size with red wale marking and/or the presence of gastric varices along the cardia were defined as HR-EGV. Clinical data were collected and previously reported prediction indices for varices were calculated. Results: Liver stiffness and SS were obtained from all patients. Fourteen patients showed HR-EGV. Significantly different variables between patients with and without HR-EGV were as follows: spleen diameter (116 mm vs. 95 mm), clinical prediction rule (104.7 vs. 124.7), King's variceal prediction score (78.8 vs. 99.4), aspartic aminotransferase-to-platelet ratio index (2.03 vs. 0.98), LS (2.63 m/s vs. 1.87 m/s), and SS (4.44 m/s vs. 3.69 m/s). The highest area under the receiver operating characteristic curve for detecting HR-EGV was that for SS (0.900), and the cut-off SS of 4.12 m/s yielded 92.9% sensitivity and 90% specificity. The intraclass correlation coefficient for intra-observer reproducibility was 0.828. Conclusions: Spleen stiffness from 2D-SWE offered the most accurate predictor of HR-EGV in BA children.

DOI： 10.1111/hepr.13381

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

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