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1. Useful Predictor for Exacerbation of Esophagogastric Varices after Hepatitis C Virus Eradication by Direct-Acting Antivirals

Author

Yuko Nagaoki, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Hiroshi Aikata, C. Nelson Hayes, Masataka Tsuge, and Shiro Oka

Subjects
direct-acting antiviral, sustained virological response, esophagogastric varices, liver stiffness measurement, total bile acid, left gastric vein, Medicine (General), R5-920
Abstract

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase.

Published
2024
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2. Asian Neonatal Network Collaboration (AsianNeo): a study protocol for international collaborative comparisons of health services and outcomes to improve quality of care for sick newborn infants in Asia – survey, cohort and quality improvement studies

Author

Yumi Kono, Hidehiko Nakanishi, Satoshi Kusuda, Hirokazu Arai, Maki Sato, Hiroaki Imamura, Takahide Yanagi, Moriharu Sugimoto, Hiroshi Matsumoto, Takashi Nakano, Satoshi Watanabe, Tomoaki Ioroi, Shigeharu Hosono, Makoto Nabetani, Osuke Iwata, Naho Morisaki, Bin Huey Quek, Kaoru Okazaki, Hideaki Harada, Masaki Kobayashi, Yuh-Jyh Lin, Yayoi Miyazono, Isamu Hokuto, Hiroshi Komatsu, Hiroshi Suzuki, Chayatat Ruangkit, Yuko Maruyama, Daisuke Nishi, Shanika Kosarat, Kapila Jayaratne, Tetsuya Isayama, Toshinori Nakashima, Tsutomu Ogata, Takashi Yamagami, Zubair Amin, Shinya Hirano, Seiji Yoshimoto, Chih-Cheng Chen, Yuji Ito, Rinawati Rohsiswatmo, Pertin Sianturi, Rocky Wilar, Dwi Hidayah, Risa Etika, Afifa Ramadanti, Pudji Andayani, Ema Alasiry, Ellen Sianipar, Yosuke Shima, Takashi Tachibana, Takahiro Okutani, Soon Min Lee, Hitoshi Yoda, Ichiro Morioka, Woei Bing Poon, Asao Yara, Akira Nishimura, Masato Ito, Tadayuki Kumagai, Hiroshi Yoshida, Takashi Okuno, Mei-Jy Jeng, Ee-Kyung Kim, Buranee Swatesutipun, Kei Inomata, Yuichi Kato, Kiyoaki Sumi, Atsushi Uchiyama, Narongsak Nakwan, Juyoung Lee, Keiji Goishi, Hiroshi Yamamoto, Hsiu-Ling Chen, Masahiro Kobayashi, Kazumasa Takahashi, Masayuki Ochiai, Fumihiko Ishida, Seok Chiong Chee, Siew Hong Neoh, Ee Lee Ang, Ann Cheng Wong, Masaru Shirai, Toru Ishioka, Toshihiko Mori, Toru Huchimukai, Kyone Ko, Akira Shimazaki, Tatsuya Yoda, Azusa Kobayashi, Yasushi Uchida, Mitsuhiro Ito, Kuniko Ieda, Toshiyuki Ono, Masashi Hayashi, Kanemasa Maki, Kozue Shiomi, Koji Nozaki, Taho Kim, Yasuyuki Tokunaga, Akihiro Takatera, Hiroshi Sumida, Yae Michinomae, Yoshio Kusumoto, Takeshi Morisawa, Tamaki Ohashi, Takahiko Saijo, Kosuke Koyano, Mikio Aoki, Koichi Iida, Mitsushi Goshi, Miho Sato, Hung-Yang Chang, Hironobu Tokumasu, Yoichi Kondo, Arif Budiman, Arief Budiman, Ken Nagaya, Fumihiko Namba, Yun Sil Chang, Masaru Yamakawa, Atsushi Nakao, Masaki Shimizu, Ming-Chih Lin, Jui-Hsing Chang, Shu-Chi Mu, Hung-Chih Lin, Fuyu Miyake, Rizalya Dewi, Yuri Ozawa, Seiichi Tomotaki, Ma Lourdes S Imperial, Belen Amparo E Velasco, Su Jin Cho, YoungAh Youn, Saman Kumara, Hsiang Yu Lin, Pracha Nuntnarumit, Sopapan Ngerncham, Chatchay Prempunpong, Pathaporn Prempraphan, Sarayut Supapannachart, Isra Firmansyah, Eny Yantri, Henri Azis, Ied Imelda, Mustarim ­, Benny Sana Putra, Leni Ervina Jumnalis, Andhika Tiurmaida Hutapea, Nadia Dwi Insani, Agnes Yunie Purwita Sari, Naomi Esthernita Dewanto, Thomas Harry Adoe, Tetty Yuniarti, Adhie Nur Radityo S, Tunjung Wibowo, Kartika Darma Handayani, Dina Djojo Husodo, Brigitta Ida Resita Vebrianti Corebima, Retno Wulandari, Made Sukmawati, I Ketut Adi Wirawan, Made Yuliari, James Thimoty, Sandra Bulan, Takashi Nasu, Yukiteru Tachibana, Ayumu Noro, Toshiya Saito, Yosuke Kaneshi, Nobuko Shiono, Nobuhiro Takahashi, Yusuke Ohkado, Tatsuro Satomi, Mika Nakajima, Eiki Nakamura, Tomofumi Ikeda, Genichiro Sotodate, Mari Ishii, Takahide Hosokawa, Rikio Suzuki, Masatoshi Sanjo, Michiya Kudo, Takushi Hanita, Satoshi Niwa, Masanari Kawamura, Yousuke Sudo, Tsutomu Ishii, Takashi Imamura, Yoshiya Yukitake, Goro Asada, Yasuaki Kobayashi, Yasushi Oki, Kenji Ichinomiya, Toru Fujiu, Hideaki Fukushima, Tetsuya Kunikata, Chika Morioka, Motoichiro Sakurai, Naoto Nishizaki, Satoshi Toishi, Harumi Otsuka, Masahiko Sato, Kenichiro Hirakawa, Kenichiro Hosoi, Hiromichi Shoji, Atsuo Miyazawa, Yuko Nagaoki, Naoki Ito, Ken Masunaga, Reiko Kushima, Sakae Kumasaka, Manabu Sugie, Daisuke Haruhara, Satsuki Kakiuchi, Riki Nishimura, Daisuke Ogata, Ayako Fukuyama, Kuriko Nakamura, Kanji Ogo, Masahiko Murase, Katsuaki Toyoshima, Maha Suzuki, Yoshio Shima, Atsushi Nemoto, Yukihide Miyosawa, Takehiko Hiroma, Gen Kuratsuji, Yoshihisa Nagayama, Tohei Usuda, Rei Kobayashi, Takeshi Hutani, Taketoshi Yoshida, Kazuhide Ohta, Shuya Nagaoki, Yasuhisa Ueno, Toru Ando, Ritsuyo Taguchi, Takeshi Arakawa, Shinji Usui, Tokuso Murabayashi, Shigeru Oki, Reiji Nakano, Taizo Ueno, Masami Shirai, Akira Oishi, Hikaru Yamamoto, Hiroshi Takeshita, Koji Takemoto, Masashi Miyata, Makoto Ohshiro, Masanori Kowaki, Osamu Shinohara, Yasunori Koyama, Takahiro Muramatsu, Akinobu Taniguchi, Naoki Kamata, Hiroshi Uchizono, Kenji Nakamura, Masahito Yamamoto, Jitsuko Ohira, Machiko Sawada, Ryosuke Araki, Daisuke Kinoshita, Ryuji Hasegawa, Shinsuke Adachi, Toru Yamakawa, Masahiko Kai, Hirotaka Minami, Kenji Mine, Reiko Negi, Satoru Ogawa, Ryoko Yoshinare, Atsushi Ogihara, Satoshi Onishi, Hiroyuki Ichiba, Misao Yoshii, Hitomi Okabe, Hiroshi Mizumoto, Masaaki Ueda, Kazumichi Fujioka, Takeshi Utsunomiya, Toshiya Nishikubo, Ken Kumagaya, Akiko Tamura, Masumi Miura, Yuki Hasegawa, Rie Kanai, Kei Takemoto, Koichi Tsukamoto, Misao Kageyama, Rie Fukuhara, Yutaka Nishimura, Seiichi Hayakawa, Yasuhiko Sera, Masahiro Tahara, Shinosuke Fukunaga, Keiko Hasegawa, Hiroshi Tateishi, Tomomasa Terada, Toru Kuboi, Osamu Matsuda, Shinosuke Akiyoshi, Takahiro Motoki, Yusei Nakata, Toshiharu Hikino, Shutaro Suga, Mitsuaki Unno, Hiroshi Kanda, Yasushi Takahata, Hiroyasu Kawano, Takayuki Kokubo, Toshimitsu Takayanagi, Muneichiro Sumi, Fumiko Kinoshita, Masanori Iwai, Naoki Fukushima, Yuki Kodama, Shuichi Yanagibe, Takuya Tokuhisa, Yoriko Kisato, Tatsuo Oshiro, Kazuhiko Nakasone, ChangWon Choi, Young-Ah Youn, Jae Won Shim, Jang Hoon Lee, Ga Won Jeon, Byong Sop Lee, Jin A Lee, Jae Woo Lim, Zuraidah Abdul Latif, Zainah Shaikh Hedra, Baizura Jamaluddin, Hasri Hafidz, Zainab Ishak, Geok Hoon Ngian, Chiong Hung Kiew, Mehala Devi Baskaran, Maslina Mohamad, Chee Sing Wong, Rozitah Razman, Maneet Kaur, Choo Hau Lim, Maizatul Akmar, Sheila Gopal Krishnan, Chae Hee Chieng, Chong Meng Choo, Eric Boon- Kuang Ang, AngShiau Chuen Diong, Angeline Seng- Lian Wan, Sharifah Huda Engku Alwi, Kwee Ching See, Rohani Abdul Jalil, Agnes Suganthi, Mei Ling Lee, Pauline Poh-Ling Choo, Lee Ser Chia, Azanna Ahmad Kamar, Anand Mohan A/L Mohana Lal, Agnes Huei- Hwen Foo, Abdul Nasir Mohamed Abdul Kadher, Ma. Lourdes Imperial, Belen Velasco, Ma. Esterlita V. Uy, Daisy Evangeline Garcia, Jacinto Blas Mantaring, Nethmini Thenuwara, Ming-Chou Chiang, Lan-Wan Wang, Xiao-Ping Wang, Yi-Li Hung, Yung Chieh Lin, Pen-Hua Su, Yung-Ning Yang, Po-Nein Tsao, Liang-Ti Huang, Yi-Yu Su, Shau-Ru Ho, Yan-Yan Ng, Kai-Ti Tseng, Yi-Yin Chen, Tsung-Yu Wu, Wei-Tse Chiu, Li-Jung Fang, Kao-Hsian Hsieh, Anavat Bupphachareonsuk, Anchalee Limrungsikul, Anita Luvira, Anucha Thatrimontrichai, Buranee Yangthara, Cholticha Laohajeeraphan, Hathitip Chaiprapa, Junya Jirapradittha, Kanmalee Jenjarat, Kannikar Booranavanich, Namtip Intub, Patcharin Thanomsingh, Pirarat Kotcharit, Piyawan Phummaphuti, Pornpimon Janyoungsak, Prapaiporn Chongkongkiat, Rapeephun Hansuebsai, Roongrawee Torbunsupachai, Santi Punnahitanan, Sommon Jindakul, Sopida Tanthawat, Sudarat Sirichaipornsak, Sudatip Kositamongkol, Supamas Supabanpot, Suparat Tipprasert, Tanin Pirunnet, Thanatda Siriporn, Usakorn Taesiri, Vasita Jirasakuldech, and Eleanor DR Cuarte

Subjects
Medicine
Abstract

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

Published
2024
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3. A single site study to investigate the current prevalence of anti‐hepatitis C virus antibody among substance use disorder patients in Hiroshima—Insufficient testing and diagnosis

Author

Ariyuki Kagaya, Yuko Nagaoki, Satomi Shimura, Katsuyoshi Kawana, and Kazuaki Chayama

Subjects
harm reduction, HCV seroprevalence, hepatitis C virus, people who inject drugs, people who use drugs, Therapeutics. Pharmacology, RM1-950, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Aims Hepatitis C virus (HCV) infection among drug users presents an important public health problem; however, little recognition and few approaches to address this issue in Japan. This study was conducted to investigate the current disease status by assessing anti‐HCV antibody (Ab) seroprevalence among people who inject drugs (PWIDs) and people who use drugs (PWUDs) in Hiroshima, Japan. Methods This study was a psychiatric single‐site chart review in patients with drug abuse problems in the Hiroshima region. The primary outcome was anti‐HCV Ab prevalence among PWIDs who underwent anti‐HCV Ab testing. The secondary outcomes included the prevalence of anti‐HCV Ab among PWUDs who underwent anti‐HCV Ab testing and the proportion of patients who underwent anti‐HCV Ab examination. Results A total of 222 PWUD patients were enrolled. Among these, 16 patients (7.2%) had records of injection drug use (PWIDs). Eleven (68.8%) of the 16 PWIDs received anti‐HCV Ab tests, and 4 (36.4%, 4/11) were anti‐HCV Ab‐positive. Among 222 PWUDs, 126 (56.8%) patients received anti‐HCV Ab tests, and 57 of these patients (45.2%, 57/126) were anti‐HCV Ab‐positive. Conclusion The prevalence of anti‐HCV Ab among PWIDs and PWUDs who visited the study site was higher than the general population, which was 2.2% among hospitalized patients between May 2018 and November 2019. Considering the World Health Organization's (WHO) elimination goal and recent advances in HCV treatment, patients with drug abuse experience should be encouraged to take HCV tests and consult hepatologists for further investigations and treatment if they are positive for anti‐HCV Ab.

Published
2023
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4. Impact of labor analgesia on mode of delivery and neonatal outcomes in Japan: A retrospective cohort study.

Author

Shu Eguchi, Yuko Nagaoki, Sachiko Ohde, and Michio Hirata

Subjects
Medicine, Science
Abstract

Labor analgesia (LA) is associated with the potential hazard of high-risk delivery, such as cesarean section (CS) and instrumental vaginal delivery (IVD), and adverse neonatal outcomes such as neonatal asphyxia and respiratory distress. The objective was to examine the impact of LA on mode of delivery and neonatal outcomes and to counsel pregnant women about a potentially higher risk and allow them to decide LA or non-LA. This retrospective cohort study containing 5,184 pregnant women analyzed the association between LA and both mode of delivery and neonatal outcomes. LA increased the risk of IVD (Adjusted Odds Ratio [AOR] 3.25, 95% confidence interval [95%CI] 2.51-4.20) but decreased that of CS (AOR 0.52, 95%CI 0.44-0.60). Two factors (advanced maternal age [AOR 1.70, 95%CI 1.33-2.17] and primipara [AOR 4.72, 95%CI 3.30-6.75]) increased the risk of IVD. We should carefully consider the indication of LA for cases with these two factors since LA can increase the risk of IVD and adverse neonatal outcomes.

Published
2023
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5. Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Author

Yuko Nagaoki, Hideyuki Hyogo, Yuwa Ando, Yumi Kosaka, Shinsuke Uchikawa, Yuno Nishida, Yuji Teraoka, Kei Morio, Hatsue Fujino, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Wataru Okamoto, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Daiki Miki, Michio Imamura, Shoichi Takahashi, Kazuaki Chayama, and Hiroshi Aikata

Subjects
HCC, NBNC-HCC, NASH, Cryptogenic, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P

Published
2021
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6. Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial

Author

Masahiro Hatooka, Tomokazu Kawaoka, Hiroshi Aikata, Yuki Inagaki, Kei Morio, Takashi Nakahara, Eisuke Murakami, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Kazuo Awai, Keiichi Masaki, Koji Waki, Hirotaka Kohno, Hiroshi Kohno, Takashi Moriya, Yuko Nagaoki, Toru Tamura, Hajime Amano, Yoshio Katamura, and Kazuaki Chayama

Subjects
HCC, HAIC, Sorafenib, Tumor marker, RECIST, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. Methods Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. Results Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. Conclusion Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

Published
2018
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7. Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring.

Author

Fumi Honda, Akira Hiramatsu, Hideyuki Hyogo, Hiroshi Aikata, Kana Daijo, Yuji Teraoka, Yuki Inagaki, Kei Morio, Tomoki Kobayashi, Takashi Nakahara, Yuko Nagaoki, Tomokazu Kawaoka, Masayasu Yoneda, Masataka Tsuge, Michio Imamura, Yoshiiku Kawakami, Hidenori Ochi, and Kazuaki Chayama

Subjects
Medicine, Science
Abstract

The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM).A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels.Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels.The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

Published
2018
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8. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy.

Author

Yuko Nagaoki, Michio Imamura, Hiroshi Aikata, Kana Daijo, Yuji Teraoka, Fumi Honda, Yuki Nakamura, Masahiro Hatooka, Reona Morio, Kei Morio, Hiromi Kan, Hatsue Fujino, Tomoki Kobayashi, Keiichi Masaki, Atsushi Ono, Takashi Nakahara, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Yoshiiku Kawakami, C Nelson Hayes, Daiki Miki, Hidenori Ochi, and Kazuaki Chayama

Subjects
Medicine, Science
Abstract

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10-196) and 23 (range 4-78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Published
2017
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9. Third-Generation Capsule Endoscopy Outperforms Second-Generation Based on the Detectability of Esophageal Varices

Author

Sayoko Kunihara, Shiro Oka, Shinji Tanaka, Ichiro Otani, Atsushi Igawa, Yuko Nagaoki, Hiroshi Aikata, and Kazuaki Chayama

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aim. The third-generation capsule endoscopy (SB3) was shown to have better image resolution than that of SB2. The aim of this study was to compare SB2 and SB3 regarding detectability of esophageal varices (EVs). Methods. Seventy-six consecutive liver cirrhosis patients (42 men; mean age: 67 years) received SB3, and 99 (58 men; mean age, 67 years old) received SB2. All patients underwent esophagogastroduodenoscopy within 1 month prior to capsule endoscopy as gold standard for diagnosis. The diagnosis using SB3 and SB2 for EVs was evaluated regarding form (F0–F3), location (Ls, Lm, and Li), and the red color (RC) sign of EVs. Results. SB2 and SB3 did not significantly differ on overall diagnostic rates for EV. Sensitivity, specificity, positive predictive value, and negative predictive value of SB2/SB3 for EV diagnosis were, respectively, 65%/81%, 100%/100%, 100%/100%, and 70%/62%. However, the diagnostic rates for EV form F1 were 81% using SB3 and 52% using SB2 (P=0.009). Further, the diagnostic rates for Ls/Lm varices were 79% using SB3 and 81% using SB2, and, for Li, varices were 84% using SB3 and 52% using SB2 (P=0.02). Conclusion. SB3 significantly improved the detectability of EVs compared with SB2.

Published
2016
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10. Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Author

Hiroshi Aikata, Kei Morio, Michio Imamura, Daiki Miki, Takashi Nakahara, Hideyuki Hyogo, Yuno Nishida, Yuwa Ando, Shinsuke Uchikawa, Atsushi Ono, Masataka Tsuge, Akira Hiramatsu, Shoichi Takahashi, Kazuaki Chayama, Tomokazu Kawaoka, Hatsue Fujino, Yuji Teraoka, Wataru Okamoto, Yuko Nagaoki, Masami Yamauchi, Eisuke Murakami, and Yumi Kosaka

Subjects
Liver Cirrhosis, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Carcinoma, Hepatocellular, NBNC-HCC, RC799-869, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Risk factor, HCC, Aged, business.industry, Incidence (epidemiology), Incidence, Liver Neoplasms, NASH, General Medicine, Hepatology, Diseases of the digestive system. Gastroenterology, medicine.disease, digestive system diseases, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Etiology, 030211 gastroenterology & hepatology, Cryptogenic, Metabolic syndrome, business, Research Article
Abstract

Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P Conclusions The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Published
2021

11. Efficacy of Lusutrombopag for Thrombocytopenia in Patients with Chronic Liver Disease Scheduled to Undergo Invasive Procedures

Author

Hideaki Kodama, Hatsue Fujino, Hiroshi Aikata, Keiko Arataki, Kei Morio, Keiji Tsuji, Maiko Namba, Masataka Tsuge, Michio Imamura, Koji Kamada, Takayuki Fukuhara, Yasutoshi Fujii, Kazuki Ohya, Yuko Nagaoki, Masami Yamauchi, Kana Daijo, C. Nelson Hayes, Yasuyuki Aisaka, Takashi Nakahara, Shoichi Takahashi, Kazuaki Chayama, Tomokazu Kawaoka, Yuji Teraoka, Yuno Nishida, Shinsuke Uchikawa, and Akira Hiramatsu

Subjects
Agonist, medicine.medical_specialty, Multivariate analysis, medicine.drug_class, thrombocytopenia, thrombopoietin receptor agonist, Chronic liver disease, Gastroenterology, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Platelet, Retrospective Studies, Thrombopoietin receptor, lusutrombopag, business.industry, Liver Diseases, chronic liver disease, Retrospective cohort study, General Medicine, Odds ratio, medicine.disease, Thiazoles, Cinnamates, Chronic Disease, diabetes mellitus, Original Article, business, Receptors, Thrombopoietin
Abstract

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×104/μL before lusutrombopag treatment to 7.2×104/μL before the invasive procedure (p

Published
2021

12. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byun, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, Maria Consiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton V.J. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris D.J. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom J.W. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch'ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, and Charles Millson

Subjects
Science & Technology, Hepatology, Gastroenterology & Hepatology, Italian PBC Study Group, Japan-PBC-GWAS Consortium, UK-PBC Consortium, Chinese PBC Consortium, 1103 Clinical Sciences, US PBC Consortium, Canadian PBC Consortium, Life Sciences & Biomedicine, PBC Consortia, 1117 Public Health and Health Services
Published
2021

13. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

14. Increase of non- HBV, non- HCV related hepatocellular carcinoma -Over 20 years single institution study

Author

Yuko Nagaoki, Hideyuki Hyogo, Yuwa Ando, Yumi Kosaka, Shinsuke Uchikawa, Yuno Nishida, Yuji Teraoka, Kei Morio, Hatsue Fujino, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Wataru Okamoto, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Daiki Miki, Michio Imamura, Shoichi Takahashi, Kazuaki Chayama, and Hiroshi Aikata

Subjects
digestive system diseases
Abstract

Background: We previously reported the trends of etiologies of hepatocellular carcinoma (HCC) between 1995 and 2009. By updating this study, we aimed to evaluate the incidence of HCC with non- hepatitis B viral and non- hepatitis C viral (NBNC) etiologies and explore the clinical characteristics, also.Methods: Consecutive 2171 HCC patients at our institution were enrolled between 1992 and 2018 in this retrospective cohort study. A comparative study was conducted by dividing into two groups, an early group from 1992 to 2009 and a late group from 2010 to 2018.Results: NBNC-HCC account for 514 patients (23.6%). The proportion of NBNC-HCC has continued to increase from 26.5% in 2009 to 46.3% in 2018. NBNC-HCC were getting older (median ages, 67 to 73 years). Type 2 diabetes mellitus (48.5% to 60.3%: P=0.008), hypertension (48.5% to 57.4%: P=0.047), and hyperlipidemia (39.2% to 53.8%: P=0.001) has increased significantly in recent years. The median FIB-4 index have decreased (4.37 to 3.61: P=0.026) and the median platelet counts have increased (15.1 to 17.9: P=0.013) significantly. Among 514 NBNC-HCC, 194 patients underwent hepatic resection in which 14.9%, 29.3%, and 55.8% were based on nonalcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), and cryptogenic, respectively. Cirrhosis was detected in 72.4%, 38.6%, and 15.5% of NASH, ALD and cryptogenic, respectively. The prevalence of cirrhosis in NASH were significantly higher than other groups (PConclusions: NBNC-HCC has rapidly been increasing in recent years even in regional university hospital. The presence of metabolic syndrome may be important risk factors. Furthermore, HCC from non-cirrhotic liver needs attention carefully. Accordingly, it is speculated that these patients should receive periodic surveillance for HCC development.

Published
2020

15. Increase of non-HBV, non-HCV related hepatocellular carcinoma - Over 20 years single institution study

Author

Masataka Tsuge, Hatsue Fujino, Yuno Nishida, Shinsuke Uchikawa, Shoichi Takahashi, Atsushi Ono, Kazuaki Chayama, Akira Hiramatsu, Tomokazu Kawaoka, Hideyuki Hyogo, Yumi Kosaka, Yuwa Ando, Daiki Miki, Takashi Nakahara, Yuji Teraoka, Hiroshi Aikata, Michio Imamura, Kei Morio, Wataru Okamoto, Eisuke Murakami, Yuko Nagaoki, and Masami Yamauchi

Subjects
Oncology, medicine.medical_specialty, business.industry, Internal medicine, Hepatocellular carcinoma, medicine, Single institution, medicine.disease, business, digestive system diseases
Abstract

Background We previously reported the trends of etiologies of hepatocellular carcinoma (HCC) between 1995 and 2009. By updating this study, we aimed to evaluate the incidence of HCC with non- hepatitis B viral and non- hepatitis C viral (NBNC) etiologies and also explore the clinical characteristics. Methods Consecutive 2171 HCC patients at our institution were enrolled between 1992 and 2018 in this retrospective cohort study. A comparative study was conducted by dividing into two groups, an early group from 1992 to 2009 and a late group from 2010 to 2018. Results NBNC-HCC account for 514 patients (23.6%). The proportion of NBNC-HCC has continued to increase from 26.5% in 2009 to 46.3% in 2018. NBNC-HCC were getting older (median ages, 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) has increased significantly in recent years. The median FIB-4 index have decreased (4.37 to 3.61: P = 0.026) and the median platelet counts have increased (15.1 to 17.9: P = 0.013) significantly. Among 514 NBNC-HCC, 194 patients underwent hepatic resection in which 14.9%, 29.3%, and 55.8% were based on nonalcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), and cryptogenic, respectively. Cirrhosis was detected in 72.4%, 38.6%, and 15.5% of NASH, ALD and cryptogenic, respectively. The prevalence of cirrhosis in NASH were significantly higher than other groups (P

Published
2020

16. A case of thrombotic microangiopathy (TMA) after transcatheter arterial chemoembolization for hepatocellular carcinoma using cisplatin

Author

Michio Imamura, Takahiko Miyama, Tatsuo Ichinohe, Yuko Nagaoki, Kazuaki Chayama, Ken Hiramatsu, Tomokazu Kawaoka, Masataka Tsuge, Takashi Nakahara, Yoshiiku Kawakami, Kazuki Ohya, and Hiroshi Aikata

Subjects
Cisplatin, medicine.medical_specialty, Thrombotic microangiopathy, Hepatology, business.industry, 030232 urology & nephrology, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepatocellular carcinoma, Internal medicine, medicine, 030212 general & internal medicine, business, Transcatheter arterial chemoembolization, medicine.drug
Published
2017

17. Exacerbation of Portal Hypertensive Enteropathy after Endoscopic Injection Sclerotherapy for Esophageal Varices

Author

Hiroshi Aikata, Sumio Iio, Shinji Tanaka, Akiyoshi Tsuboi, Kazuaki Chayama, Sayoko Kunihara, Shiro Oka, Ichiro Otani, and Yuko Nagaoki

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Exacerbation, medicine.medical_treatment, Esophageal and Gastric Varices, Gastroenterology, Capsule Endoscopy, 03 medical and health sciences, 0302 clinical medicine, Esophageal varices, Internal medicine, Edema, Sclerotherapy, Medicine, Humans, Enteropathy, Ligation, Aged, business.industry, Collateral circulation, medicine.disease, Stenosis, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.symptom, business, Gastrointestinal Hemorrhage
Abstract

Introduction: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. Methods: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. Results: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. Conclusions: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.

Published
2019

18. Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan

Author

Sakae Kumasaka, Kenji Ihara, Yoshinori Kohno, Hiroko Arai, Makoto Kuwashima, Kazuhiro Ohkubo, Tokuo Miyazawa, Kazuo Sato, Maiko Misaki, Yuko Nagaoki, Masayuki Ochiai, Masahiko Kawai, Takeshi Futatani, Kanemasa Maki, Shinichi Watabe, Naoko Toda, Hiroshi Mizumoto, Toshiro Hara, Yutaka Kawamoto, Nobuhiro Takahashi, Yasuhisa Ueno, Setsuko Nakata, Yutaka Sumida, Atsushi Komatsu, Yukari Yada, Maki Sato, Akihiko Kawase, and Kanako Kojima-Ishii

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Pediatrics, Beckwith-Wiedemann Syndrome, Perinatal care, 030209 endocrinology & metabolism, 030105 genetics & heredity, Hypoglycemia, medicine.disease_cause, Nationwide survey, 03 medical and health sciences, 0302 clinical medicine, Japan, Pregnancy, Hyperinsulinism, Surveys and Questionnaires, Internal medicine, Genetics, medicine, Humans, Abnormalities, Multiple, Genetic Testing, Hyperinsulinemic hypoglycemia, Genetics (clinical), Beckwith wiedemann, Hematologic Tests, Sotos Syndrome, Sotos syndrome, business.industry, Infant, Newborn, medicine.disease, Hematologic Diseases, Pregnancy Complications, Phenotype, Endocrinology, Vestibular Diseases, Face, Population Surveillance, Apgar Score, Female, Congenital overgrowth, business, Kabuki syndrome
Abstract

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Published
2016

19. ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C

Author

Yoshiiku Kawakami, Hiroyuki Ito, Yuko Nagaoki, Kazuaki Chayama, Keiji Tsuji, Hidenori Ochi, Clair Nelson Hayes, Hajime Amano, Toru Tamura, Akira Hiramatsu, Tomokazu Kawaoka, Masataka Tsuge, Michio Imamura, Hiroshi Aikata, Kei Morio, Grace Naswa Makokha, Takashi Nakahara, Koji Waki, Hiroshi Kohno, Keiko Arataki, Takashi Moriya, and Toshio Nakamura

Subjects
Adult, Male, medicine.medical_specialty, Cirrhosis, Genotype, Sofosbuvir, Anemia, Hepacivirus, Antiviral Agents, Polymorphism, Single Nucleotide, Gastroenterology, Hemoglobins, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Ribavirin, Humans, Medicine, Pyrophosphatases, Aged, Aged, 80 and over, Intention-to-treat analysis, Dose-Response Relationship, Drug, business.industry, Odds ratio, Hepatitis C, Chronic, Middle Aged, medicine.disease, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, ITPA, business, medicine.drug
Abstract

Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown. Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR). Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index

Published
2016

20. IFNL4polymorphism effects on outcome of simeprevir, peginterferon, and ribavirin therapy for older patients with genotype 1 chronic hepatitis C

Author

Daiki Miki, Yohji Honda, Michio Imamura, C. Nelson Hayes, Hidenori Ochi, Keiji Tsuji, Nami Mori, Kazuaki Chayama, Tomokazu Kawaoka, Yoshiiku Kawakami, Shintaro Takaki, Masataka Tsuge, Akira Hiramatsu, Yuko Nagaoki, and Hiroshi Aikata

Subjects
0301 basic medicine, Simeprevir, Treatment response, medicine.medical_specialty, Hepatology, business.industry, Ribavirin, Single-nucleotide polymorphism, Virology, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, chemistry, Older patients, Multicenter study, Chronic hepatitis, Internal medicine, Genotype, Medicine, 030211 gastroenterology & hepatology, business
Abstract

Aim Older patients with chronic hepatitis C have a lower virological response to interferon (IFN)-based treatments compared to younger patients. A single nucleotide polymorphism in the IFN-λ-4 (IFNL4) gene has a potent predictive effect on treatment response to IFN-based treatments. The efficacy of simeprevir (SMV) plus pegylated-IFN (PEG-IFN) and ribavirin therapy and the predictive value of IFNL4 on the outcome of therapy for older patients have not been addressed. Methods This retrospective multicenter study included 234 consecutive Japanese patients with genotype 1 chronic hepatitis C. We assessed the predictive factors for sustained virological response (SVR) to SMV, PEG-IFN, and ribavirin triple therapy in 170 younger (

Published
2016

21. Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial

Author

Eisuke Murakami, Yuki Inagaki, Hirotaka Kohno, Yuko Nagaoki, Masahiro Hatooka, Toru Tamura, Koji Waki, Takashi Nakahara, Keiichi Masaki, Yoshio Katamura, Michio Imamura, Akira Hiramatsu, Masataka Tsuge, Hiroshi Aikata, Hajime Amano, Kazuaki Chayama, Tomokazu Kawaoka, Kazuo Awai, Yoshiiku Kawakami, Hiroshi Kohno, Kei Morio, and Takashi Moriya

Subjects
Male, Cancer Research, Phases of clinical research, Kaplan-Meier Estimate, Gastroenterology, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, HCC, Aged, 80 and over, education.field_of_study, Liver Neoplasms, Middle Aged, Sorafenib, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, HAIC, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, Fluorouracil, Research Article, medicine.drug, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, Genetics, Humans, Infusions, Intra-Arterial, Tumor marker, education, Adverse effect, Survival rate, Aged, Proportional Hazards Models, business.industry, medicine.disease, digestive system diseases, RECIST, Cisplatin, business, Progressive disease
Abstract

Background In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. Methods Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. Results Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. Conclusion Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

Published
2018

22. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy

Author

Fumi Honda, C. Nelson Hayes, Kana Daijo, Hiromi Kan, Yoshiiku Kawakami, Yuko Nagaoki, Hidenori Ochi, Daiki Miki, Keiichi Masaki, Masataka Tsuge, Reona Morio, Kei Morio, Tomoki Kobayashi, Hatsue Fujino, Yuji Teraoka, Michio Imamura, Yuki Nakamura, Takashi Nakahara, Masahiro Hatooka, Kazuaki Chayama, Hiroshi Aikata, Tomokazu Kawaoka, Atsushi Ono, and Akira Hiramatsu

Subjects
RNA viruses, Chronic Hepatitis, Pyrrolidines, lcsh:Medicine, Aminotransferases, Kaplan-Meier Estimate, Hepacivirus, medicine.disease_cause, Gastroenterology, Biochemistry, Chronic Liver Disease, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Public and Occupational Health, lcsh:Science, Pathology and laboratory medicine, Aged, 80 and over, Sulfonamides, Multidisciplinary, Protease Inhibitor Therapy, Alcohol Consumption, Hepatitis C virus, Incidence, Liver Diseases, Liver Neoplasms, Imidazoles, Valine, Hepatitis C, Middle Aged, Viral Load, Medical microbiology, Vaccination and Immunization, Enzymes, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Viruses, Liver Fibrosis, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Pathogens, Viral load, medicine.drug, Research Article, Adult, medicine.medical_specialty, Daclatasvir, Carcinoma, Hepatocellular, Immunology, Antiretroviral Therapy, Gastroenterology and Hepatology, Antiviral Agents, Carcinomas, Microbiology, 03 medical and health sciences, Young Adult, Pharmacotherapy, Antiviral Therapy, Transferases, Internal medicine, Ribavirin, Gastrointestinal Tumors, medicine, Humans, Aged, Proportional Hazards Models, Nutrition, Biology and life sciences, Flaviviruses, business.industry, lcsh:R, Organisms, Viral pathogens, Interferon-alpha, Cancers and Neoplasms, Proteins, Hepatocellular Carcinoma, Hepatitis C, Chronic, medicine.disease, Isoquinolines, Hepatitis viruses, Microbial pathogens, Diet, chemistry, Enzymology, Asunaprevir, lcsh:Q, Carbamates, Preventive Medicine, business
Abstract

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10-196) and 23 (range 4-78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Published
2017

23. Contents Vol. 92, 2017

Author

Kazuaki Chayama, Gianluca Lo Coco, Druckerei Stückle, I. Novopashenny, Mathias Krockenberger, Margarida Afonso, Bárbara Oliveiros, Achim Wöckel, Tomokazu Kawaoka, Hiroyuki Okuyama, Michio Imamura, Hiroshi Aikata, J Diessner, Hideaki Takahashi, Masataka Tsuge, Roland Stein, Wolfgang Janni, Yusuke Hashimoto, Takashi Nakahara, Rossella Caiazzo, Masafumi Ikeda, Masahiro Hatooka, Patrizia Dorangricchia, Laura Salerno, Takuji Okusaka, Daniela Musio, Francesca De Felice, Reona Morio, Tomoki Kobayashi, Vincenzo Tombolini, Shunsuke Kondo, Kei Morio, Yuko Nagaoki, Maria Blettner, Rolf Kreienberg, Ilaria Benevento, Hideki Ueno, Catharina Bartmann, Yuki Inagaki, Shuichi Mitsunaga, Satz Mengensatzproduktion, Akira Hiramatsu, Chigusa Morizane, Sebastian Häusler, Giuseppe Cicero, Fumi Honda, Tanja Stüber, Izumi Ohno, Alice Pêgo, Yasuaki Arai, Cristiana Cruz, Rossella De Luca, Filippo Rubini, Yuji Teraoka, Yoshiiku Kawakami, Yasunari Sakamoto, Tatsushi Kobayashi, and Manfred Wischnewsky

Subjects
Cancer Research, Oncology, General Medicine
Published
2017

24. Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C

Author

Hatsue, Fujino, Michio, Imamura, Yuko, Nagaoki, Yoshiiku, Kawakami, Hiromi, Abe, C Nelson, Hayes, Hiromi, Kan, Takayuki, Fukuhara, Tomoki, Kobayashi, Keiichi, Masaki, Atsushi, Ono, Takashi, Nakahara, Youji, Honda, Noriaki, Naeshiro, Ayako, Urabe, Satoe, Yokoyama, Daisuke, Miyaki, Eisuke, Murakami, Tomokazu, Kawaoka, Nobuhiko, Hiraga, Masataka, Tsuge, Akira, Hiramatsu, Hideyuki, Hyogo, Hiroshi, Aikata, Shoichi, Takahashi, Daiki, Miki, Hidenori, Ochi, Waka, Ohishi, Kazuaki, Chayama, and Keitaro, Yamashina

Subjects
Adult, Male, medicine.medical_specialty, Genotype, Combination therapy, Hepatitis C virus, Hepacivirus, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, Polymorphism, Single Nucleotide, Gastroenterology, Polyethylene Glycols, Telaprevir, Young Adult, chemistry.chemical_compound, Pharmacotherapy, Predictive Value of Tests, Internal medicine, Ribavirin, medicine, Humans, Aged, Dose-Response Relationship, Drug, business.industry, Interleukins, Age Factors, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, Virology, Recombinant Proteins, Treatment Outcome, chemistry, Predictive value of tests, Multivariate Analysis, Regression Analysis, Drug Therapy, Combination, Female, business, Oligopeptides, medicine.drug
Abstract

Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed.We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82%, P = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9%, P = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients.Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.

Published
2013

25. Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases

Author

Keiichi Masaki, Hiroshi Aikata, Eisuke Murakami, Noriaki Naeshiro, Yuko Nagaoki, Shintaro Takaki, Michio Imamura, Takayuki Fukuhara, Daisuke Miyaki, Shoichi Takahashi, Yoji Honda, Yoshiiku Kawakami, Masataka Tsuge, Kazuaki Chayama, Nobuhiko Hiraga, Tomokazu Kawaoka, Hideyuki Hyogo, Hidenori Ochi, Takashi Nakahara, Tomoki Kobayashi, Akira Hiramatsu, Koji Arihiro, and Atsushi Ohno

Subjects
medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, Spleen, Chronic liver disease, medicine.disease, Gastroenterology, Confidence interval, Infectious Diseases, medicine.anatomical_structure, Liver steatosis, Internal medicine, Liver biopsy, medicine, Steatosis, Transient elastography, business
Abstract

Aim Steatosis is a common histological feature of chronic liver disease, especially alcoholic and non-alcoholic fatty liver disease, as well as chronic hepatitis C. A recent study showed that evaluating the controlled attenuation parameter (CAP) with transient elastography was an efficient way of non-invasively determining the severity of hepatic steatosis. The objective of this study was to prospectively evaluate the utility of CAP for diagnosing steatosis in patients with chronic liver disease. Methods One hundred and fifty-five consecutive patients with suspected chronic liver disease underwent steatosis diagnosis using CAP, blood sample analyses, computed tomography for assessing the liver/spleen ratio and liver biopsy. Steatosis was graded according to the percentage of fat-containing hepatocytes: S0, less than 5%; S1, 5–33%; S2, 34–66%; and S3: more than 66%. Results The CAP was significantly correlated with steatosis grade, and there were significant differences between the CAP value of the S0 patients and those of the patients with other grades of steatosis. S0 and S1–3 hepatic steatosis were considered to represent mild and significant steatosis, respectively. The CAP values of the patients with mild and significant steatosis were significantly different (P

Published
2013

26. A case of acute hepatitis C with hepatitis C virus (HCV) genotype 3a -discussion of IL28-B

Author

Kazuaki Chayama, Tomokazu Kawaoka, Akira Hiramatsu, Takashi Nakahara, Michihiro Nonaka, Michio Imamura, Masaki Tsuge, Hideyuki Hyogo, Hiroshi Aikata, Mio Tanaka, Yoji Honda, Shoichi Takahashi, Hidehiko Takigawa, Shintaro Takaki, Noriaki Naeshiro, Yuko Nagaoki, Tomoki Kobayashi, Daisuke Miyaki, and Yoshiiku Kawakami

Subjects
Hepatology, business.industry, Hepatitis C virus, Genotype, Medicine, Acute hepatitis C, business, medicine.disease_cause, Virology
Published
2013

27. Efficacy and safety of daclatasvir plus asunaprevir therapy for chronic hepatitis C patients with renal dysfunction

Author

Kana Daijo, Masataka Tsuge, Yuko Nagaoki, Kei Morio, Hidenori Ochi, C. Nelson Hayes, Takashi Nakahara, Fumi Honda, Michio Imamura, Yoshiiku Kawakami, Yuji Teraoka, Kazuaki Chayama, Yuki Nakamura, Tomokazu Kawaoka, Tomoki Kobayashi, Daiki Miki, Akira Hiramatsu, and Hiroshi Aikata

Subjects
Adult, Male, medicine.medical_specialty, Daclatasvir, Pyrrolidines, Combination therapy, Drug-Related Side Effects and Adverse Reactions, Sustained Virologic Response, medicine.medical_treatment, Renal function, urologic and male genital diseases, Gastroenterology, Antiviral Agents, Virus, 03 medical and health sciences, chemistry.chemical_compound, Plasma, 0302 clinical medicine, Virology, Internal medicine, medicine, Humans, Renal Insufficiency, Adverse effect, Aged, Aged, 80 and over, Sulfonamides, business.industry, Imidazoles, Valine, Hepatitis C, Chronic, Middle Aged, Viral Load, Isoquinolines, Discontinuation, Infectious Diseases, Treatment Outcome, chemistry, Withholding Treatment, 030220 oncology & carcinogenesis, Asunaprevir, 030211 gastroenterology & hepatology, Female, Hemodialysis, Carbamates, business, medicine.drug
Abstract

Chronic hepatitis C virus (HCV) infection is associated with renal dysfunction. Daclatasvir and asunaprevir combination therapy showed a high virological response for genotype 1 chronic HCV-infected patients with renal dysfunction on hemodialysis. However, the safety and efficacy of the therapy for patients with renal dysfunction who are not on hemodialysis are not well-known. In total, 147 patients with chronic HCV genotype 1 infection were treated with 24 weeks of daclatasvir plus asunaprevir therapy. Among these patients, 126 had normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 ml/min/1.73 m2) and 21 had renal dysfunction (eGFR

Published
2016

28. Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy

Author

Hiromi Kan, Tomoki Kobayashi, Yoshiiku Kawakami, Grace Naswa Makokha, Keiichi Masaki, Michio Imamura, Yizhou Zhang, Hatsue Fujino, Hiromi Abe-Chayama, C. Nelson Hayes, Atsushi Ono, Hidenori Ochi, Yuki Nakamura-Inagaki, Daiki Miki, Akira Hiramatsu, Masataka Tsuge, Kazuhiko Masuda, Takashi Nakahara, Kana Daijo, Takuro Uchida, Yuko Nagaoki, Hiroshi Aikata, Kazuaki Chayama, Tomokazu Kawaoka, Yuji Teraoka, and Kei Morio

Subjects
Sorafenib, Oncology, Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, chemical and pharmacologic phenomena, Antineoplastic Agents, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hepatic Artery, Surgical oncology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Humans, Infusions, Intra-Arterial, HMGB1 Protein, Tumor marker, Aged, Aged, 80 and over, business.industry, Liver Neoplasms, Gastroenterology, Hepatology, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Survival Rate, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Multivariate Analysis, Disease Progression, Biomarker (medicine), 030211 gastroenterology & hepatology, Female, business, Liver cancer, Progressive disease, medicine.drug
Abstract

Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis. Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis. Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P

Published
2016

29. Daytime nap controls toddlers’ nighttime sleep

Author

Kazutoshi Cho, Mari Ikeuchi, Yuriko Azami, Yoko Asaka, Miwa Ozawa, Rinshu Shimabukuro, Yuko Nagaoki, Mari Takahashi, Hitoshi Yoda, Noriko Takahashi, Takayo Nakazawa, Yoshihisa Oishi, Michio Hirata, Machiko Nakagawa, Hidenobu Ohta, Keita Morioka, Isao Kusakawa, and Yousuke Kaneshi

Subjects
Male, Pediatrics, medicine.medical_specialty, Audiology, Article, 03 medical and health sciences, 0302 clinical medicine, Nighttime sleep, Surveys and Questionnaires, mental disorders, medicine, Humans, 030212 general & internal medicine, Multidisciplinary, Sleep quality, business.industry, fungi, Infant, Actigraphy, Sleep in non-human animals, Nap, Sleep Deprivation, Late afternoon, Sleep diary, Female, Sleep onset, business, Sleep, human activities, 030217 neurology & neurosurgery, psychological phenomena and processes
Abstract

Previous studies have demonstrated that afternoon naps can have a negative effect on subsequent nighttime sleep in children. These studies have mainly been based on sleep questionnaires completed by parents. To investigate the effect of napping on such aspects of sleep quality, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents were asked to attach actigraphy units to their child’s waist by an adjustable elastic belt and complete a sleep diary for 7 consecutive days. 50 healthy young toddlers of approximately 1.5 years of age were recruited. There was a significant negative correlation between nap duration and both nighttime sleep duration and sleep onset time, suggesting that long nap sleep induces short nighttime sleep duration and late sleep onset time. We also found a significant negative correlation between nap timing and nighttime sleep duration and also a significant positive correlation between nap timing and sleep onset time, suggesting that naps in the late afternoon also lead to short nighttime sleep duration and late sleep onset. Our findings suggest that duration-controlled naps starting early in the afternoon can induce a longer nighttime sleep in full-term infants of approximately 1.5 years of age.

Published
2016
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30. Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C

Author

Akira Hiramatsu, Masataka Tsuge, C. Nelson Hayes, Hidenori Ochi, Kei Morio, Nami Mori, Satoe Yokoyama, Reona Morio, Tomoki Kobayashi, Yoshiiku Kawakami, Hiroshi Aikata, Keiji Tsuji, Daiki Miki, Yuko Nagaoki, Shintaro Takaki, Yuki Kimura, Michio Imamura, Shoichi Takahashi, Kazuaki Chayama, and Tomokazu Kawaoka

Subjects
0301 basic medicine, Simeprevir, Male, Pyrrolidines, Sustained Virologic Response, Hepacivirus, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Aged, 80 and over, education.field_of_study, Sulfonamides, Gastroenterology, Age Factors, Imidazoles, Valine, Middle Aged, Viral Load, Treatment Outcome, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.drug, Adult, medicine.medical_specialty, Daclatasvir, Combination therapy, Adolescent, Hepatitis C virus, Population, Antiviral Agents, Polymorphism, Single Nucleotide, Drug Administration Schedule, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, Drug Resistance, Viral, medicine, Humans, education, Adverse effect, Aged, business.industry, Odds ratio, Hepatitis C, Chronic, Isoquinolines, 030104 developmental biology, chemistry, Physical therapy, Asunaprevir, Carbamates, business
Abstract

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV)-infected patients. However, the safety and efficacy of the therapy for older patients are unknown. One hundred seventy patients younger than 75 years and 139 patients aged 75 years or older with genotype 1 HCV infection were treated for 24 weeks with daclatasvir plus asunaprevir. Pretreatment drug-resistance-associated variants at NS5A-L31 and NS5A-Y93 were determined by the Invader assay. Virological response and adverse events according to age were analyzed. The sustained virological response (SVR) rate for older patients was similar to that for younger patients (97.1 and 92.4 % respectively). In multivariate regression analysis, prior simeprevir treatment (odds ratio 56.6 for absence; P

Published
2016

31. Achievement of Sustained Viral Response after Switching Treatment from Pegylated Interferon a-2b to a-2a and Ribavirin in Patients with Recurrence of Hepatitis C Virus Genotype 1 Infection after Liver Transplantation: A Case Report

Author

Hidenori Ochi, Koji Waki, Akira Hiramatsu, Nobuhiko Hiraga, Shoichi Takahashi, Yoshiiku Kawakami, Kazuaki Chayama, Shintaro Takaki, Michio Imamura, Tomokazu Kawaoka, Hiroshi Aikata, Daiki Miki, Hirotaka Tashiro, Yoshio Katamura, Hideki Ohdan, Yuko Nagaoki, Yoshimasa Hashimoto, and Masataka Tsuge

Subjects
Male, medicine.medical_specialty, Genotype, medicine.medical_treatment, Hepatitis C virus, Hepacivirus, Interferon alpha-2, Liver transplantation, medicine.disease_cause, Antiviral Agents, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, Drug Therapy, Recurrence, Pegylated interferon, Interferon, Virology, Internal medicine, Ribavirin, medicine, Humans, Sequence Deletion, business.industry, Interferon-alpha, Hepatitis C, Middle Aged, Viral Load, medicine.disease, Recombinant Proteins, Liver Transplantation, Treatment Outcome, Infectious Diseases, Amino Acid Substitution, chemistry, Hepatocellular carcinoma, RNA, Viral, business, Viral load, medicine.drug
Abstract

We report a case in which sustained viral response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a sustained viral response.

Published
2012

32. Erratum to: Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy

Author

Kazuhiko Masuda, Atsushi Ono, Hiroshi Aikata, Tomokazu Kawaoka, C. Nelson Hayes, Yuji Teraoka, Kana Daijo, Yuki Nakamura-Inagaki, Kei Morio, Hatsue Fujino, Hiromi Kan, Takuro Uchida, Keiichi Masaki, Tomoki Kobayashi, Takashi Nakahara, Grace Naswa Makokha, Yizhou Zhang, Yuko Nagaoki, Daiki Miki, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Hiromi Abe-Chayama, Yoshiiku Kawakami, Hidenori Ochi, and Kazuaki Chayama

Subjects
Gastroenterology
Published
2017

33. A case report of perforation of the colon during the sorafenib therapy for hepatocellular carcinoma

Author

Yoshiiku Kawakami, Yoshimasa Hashimoto, Yuko Nagaoki, Masataka Tsuge, Hiroshi Aikata, Michio Imamura, Koji Waki, Hideyuki Hyogo, Nana Nakayama, Syoichi Takahashi, Tomokazu Kawaoka, Takahiro Azagami, Akira Hiramatsu, Koji Arihiro, Wataru Shimizu, Kazuaki Cyayama, Shintaro Takaki, Eisuke Murakami, and Daisuke Miyaki

Subjects
Sorafenib, Oncology, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Hepatocellular carcinoma, Perforation (oil well), Medicine, business, medicine.disease, Gastroenterology, medicine.drug
Abstract

症例は72歳，男性．2003年肝細胞癌初発し，RFAを施行．以後，再発癌に対し，TACEやRFAを行ってきたが，2009年1月肺転移，胸壁転移が出現した．全身化学療法を含む集学的治療を行うも奏功せず，2010年4月3日よりsorafenib 800 mg/dayを導入した．副作用として，手足皮膚反応や下痢，倦怠感が出現したため，適宜，減量，休薬にて投与量の調節を行い，11月30日よりsorafenib 400 mg/dayを投与継続中で，副作用も自制内であった．2011年1月4日，急性腹症にて救急外来受診，CTにて骨盤内にfree airを認め，腸管穿孔と診断，S状結腸切除および人工肛門造設術を施行した．術後，合併症無く経過している．肝細胞癌に対するsorafenib内服中に消化管穿孔を合併した症例を経験したので報告する．

Published
2011

34. Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring

Author

Kazuaki Chayama, Tomokazu Kawaoka, Masayasu Yoneda, Tomoki Kobayashi, Michio Imamura, Yuko Nagaoki, Hideyuki Hyogo, Masataka Tsuge, Kana Daijo, Yuji Teraoka, Takashi Nakahara, Fumi Honda, Kei Morio, Yuki Inagaki, Hidenori Ochi, Hiroshi Aikata, Yoshiiku Kawakami, and Akira Hiramatsu

Subjects
Blood Glucose, Male, 0301 basic medicine, Cirrhosis, endocrine system diseases, Physiology, lcsh:Medicine, Chronic liver disease, Biochemistry, Gastroenterology, Endocrinology, Mathematical and Statistical Techniques, 0302 clinical medicine, Liver Function Tests, Medicine and Health Sciences, Diabetes diagnosis and management, lcsh:Science, Aged, 80 and over, Multidisciplinary, medicine.diagnostic_test, Organic Compounds, Liver Diseases, Monosaccharides, Middle Aged, Blood Sugar, Body Fluids, Type 2 Diabetes, Chemistry, Blood, Physical Sciences, Female, Anatomy, Statistics (Mathematics), Research Article, Adult, medicine.medical_specialty, HbA1c, Endocrine Disorders, Carbohydrates, 030209 endocrinology & metabolism, Hypoglycemia, Research and Analysis Methods, Young Adult, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Hemoglobin, Statistical Methods, Aged, Glycemic, Glycated Hemoglobin, business.industry, Blood Glucose Self-Monitoring, Organic Chemistry, lcsh:R, Chemical Compounds, Biology and Life Sciences, Proteins, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, Diagnostic medicine, Glucose, 030104 developmental biology, Diabetes Mellitus, Type 2, Metabolic Disorders, Hyperglycemia, Multivariate Analysis, Chronic Disease, lcsh:Q, Liver function tests, business, Mathematics, Biomarkers
Abstract

Background and aims The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). Materials and methods A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. Results and discussion Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. Conclusion The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

Published
2018

35. Detection of Human Bocavirus 2 DNA from a Girl with Plastic Bronchitis

Author

Nobuhisa Ishiguro, Yuko Nagaoki, Takehiko Ishida, and Hideo Tsuda

Subjects
biology, Plastic bronchitis, business.industry, media_common.quotation_subject, Human bocavirus, biology.organism_classification, Virology, chemistry.chemical_compound, chemistry, Medicine, Girl, business, DNA, media_common
Published
2014

36. Successful Endoscopic en bloc Resection of a 4.5-cm Malignant Melanoma of the Esophagus

Author

Yuko Nagaoki, Yoshiro Tamegai, Naomi Uemura, Ryoko Iwashita, Kiyoshi Saito, Naohiko Masaki, and Yuichi Nozaki

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Mechanical Engineering, Melanoma, Energy Engineering and Power Technology, Medicine, En bloc resection, Management Science and Operations Research, Esophagus, business, medicine.disease, Surgery
Published
2007

37. A submucosal heterotopia of gastric glands removed by endoscopic submucosal dissection

Author

Makoto Mochiduki, Toshiyuki Sakurai, Takao Oshima, Keita Sasajima, Naoki Akazawa, Yukiko Isogai, Hideki Utagawa, Naoyoshi Nagata, Junichi Akiyama, Yuko Nagaoki, Naomi Uemura, Masao Kobayakawa, Akahito Sakoh, Takeichi Yoshida, Hidemitsu Yasuda, and Yuzo Yago

Subjects
medicine.medical_specialty, business.industry, Mechanical Engineering, General surgery, Energy Engineering and Power Technology, Endoscopic submucosal dissection, Anatomy, Management Science and Operations Research, medicine.disease, medicine.anatomical_structure, Heterotopia (medicine), Gastric glands, Medicine, business
Published
2008

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