Article
Biochemistry & Molecular Biology
Dariusz Zakrzewicz, Joachim Geyer
Summary: Hepatitis B virus infections are a major public health concern worldwide. A recently discovered high-affinity hepatic host receptor has become a key focus of research for potential therapies. This article presents a newly generated three-dimensional model of the receptor and discusses its role in the entry of HBV into hepatocytes.
Review
Pediatrics
Ting-Ting Zou, Yu Zhu, Chao-Min Wan, Qiong Liao
Summary: Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a newly reported hereditary bile acid metabolic disease, presenting most commonly with jaundice in pediatric patients. It can be detected during routine check-ups and is characterized by hypercholanemia and elevated AST. Screening for c.800C>T mutation in SLC10A1 is useful for primary genetic screening in Chinese infants with persistent hypercholanemia after infectious, structural, and immunological factors are excluded.
TRANSLATIONAL PEDIATRICS
(2021)
Article
Medicine, Research & Experimental
Takuro Uchida, Seung Bum Park, Tadashi Inuzuka, Min Zhang, Joselyn N. Allen, Kazuaki Chayama, T. Jake Liang
Summary: The NTCP-S267F variant, associated with reduced risk of HBV infection, was introduced into hepatic cells via CRISPR base editing. Homozygous clones did not support HBV infection, while heterozygous clones behaved similarly to wild-type. This study provides valuable insights for therapeutic intervention against HBV.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Pharmacology & Pharmacy
Chitra Saran, Henry Ho, Paavo Honkakoski, Kim L. R. Brouwer
Summary: The study discovered that everolimus, an mTOR inhibitor and immunosuppressive drug, can directly inhibit the function of NTCP. This finding is significant for the research and development of new medications against HBV/HDV.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Gastroenterology & Hepatology
Roni F. Kunst, Henkjan J. Verkade, Ronald P. J. Oude Elferink, Stan F. J. van de Graaf
Summary: Bile salts are essential for lipid homeostasis and can be both culprits and potential remedies in gut or liver disorders. Efficient transporters mediate the uptake and efflux of bile salts, ensuring their enterohepatic circulation. Deficiencies in key transporters can lead to pathological conditions, and targeting these pathways may offer new therapeutic opportunities.
Article
Pharmacology & Pharmacy
Dongliang Cheng, Zhiwei Wen, Hui Chen, Shiyuan Lin, Wei Zhang, Xin Tang, Wei Wu
Summary: In this study, a functionalized liposome PPP-LIP was modified to have tumor targetability and enhanced internalization after MMP2-triggered TATp exposure for liver tumor-specific delivery. The results showed that PPP-LIP was taken up more by tumor cells and had a better antitumor effect compared to commercially available injections.
Article
Virology
Masaya Nanahara, Ya-Ting Chang, Masaharu Somiya, Shun'ichi Kuroda
Summary: The study showed that Myr47 lipopeptide can reduce the cellular uptake of HBsAg and lipid nanoparticles even without NTCP expression, by anchoring and inhibiting the interaction of these particles with apolipoproteins through its myristoyl residue. This suggests that Myr47 may have potential as an anti-HBV drug by preventing HBV infection.
Article
Multidisciplinary Sciences
Jinta Asami, Kanako Terakado Kimura, Yoko Fujita-Fujiharu, Hanako Ishida, Zhikuan Zhang, Yayoi Nomura, Kehong Liu, Tomoko Uemura, Yumi Sato, Masatsugu Ono, Masaki Yamamoto, Takeshi Noda, Hideki Shigematsu, David Drew, So Iwata, Toshiyuki Shimizu, Norimichi Nomura, Umeharu Ohto
Summary: Chronic infection with hepatitis B virus (HBV) requires interaction between the large glycoproteins of the virus envelope (LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP). This study reveals the structures of NTCP and identifies a possible transport route for substrate. Furthermore, the study suggests a binding mode between LHBs and NTCP, which explains naturally occurring HBV-insusceptible mutations in NTCP.
Article
Endocrinology & Metabolism
Fangji Yang, Wenxiong Xu, Lina Wu, Luo Yang, Shu Zhu, Lu Wang, Wenbin Wu, Yuzhen Zhang, Yutian Chong, Liang Peng
Summary: The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency, leading to hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities in adult individuals. NTCP deficiency is also associated with elevated levels of serum bile acids and decreased levels of vitamin D, as well as aggravated osteoporotic phenotype.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Zongmei Zheng, Jiao Wei, Xinxin Hou, Fengjing Jia, Zhaozhou Zhang, Haidong Guo, Fuwen Yuan, Feng He, Zunji Ke, Yan Wang, Ling Zhao
Summary: This study reveals a new bile acid-driven mechanism of colorectal cancer-associated liver metastasis. The accumulation of taurocholic acid (TCA) in the liver promotes liver metastasis and creates a tumor-favorable microenvironment. Blocking hepatic bile acid uptake effectively suppresses TCA-induced liver metastasis.
Article
Genetics & Heredity
Lu Yang, Di Zhou, Kaechele Martin, Jun Wu, Mingfa Chen, Mengji Lu, Dongliang Yang, Ulrike Protzer, Michael Roggendorf, Jingjiao Song
Summary: The limited host range of hepatitis B virus (HBV) has hindered research progress due to the lack of a suitable animal model. Woodchuck hepatitis virus (WHV) infection in woodchucks closely mirrors HBV infection in humans, making them a promising candidate for establishing HBV infection models. The introduction of human sodium taurocholate cotransporting polypeptide (hNTCP) into woodchuck hepatocytes showed susceptibility to hepatitis D virus (HDV) infection but not HBV, suggesting the presence of species-specific factors mediating early-stage HBV infection.
Article
Microbiology
Yingying Li, Guangxiang Luo
Summary: HBV infection is a major global health issue, with current treatments being limited. Recent research has shown that LDLR plays a crucial role in HBV infection, suggesting potential new avenues for HBV therapy. Further studies are needed to explore the involvement of other LDLR family members in HBV infection.
Article
Biochemical Research Methods
Qisong Zhang, Zhuoru He, Zhongqiu Liu, Lingzhi Gong
Summary: This study utilized a knockout mouse model to investigate the physiological functions of NTCP, revealing that its deficiency leads to significant metabolic changes in the plasma and liver of mice. Metabolomics analysis identified numerous differential metabolites in the liver and plasma, with dysregulation in multiple metabolic pathways. The findings suggest potential diagnostic biomarkers and therapeutic strategies for NTCP deficiency.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Review
Virology
Margaux J. Heuschkel, Thomas F. Baumert, Eloi R. Verrier
Summary: Chronic hepatitis D is a severe form of chronic viral hepatitis with a high risk of hepatocellular carcinoma, resulting from co-infection of the liver with HBV and HDV. Current therapies only control HBV infection, while novel strategies are needed for efficient elimination of HDV.
Article
Multidisciplinary Sciences
Khanit Sa-ngiamsuntorn, Piyanoot Thongsri, Yongyut Pewkliang, Suparerk Borwornpinyo, Adisak Wongkajornsilp
Summary: The study introduces an effective hepatocyte model for screening anti-HBV drugs targeting both pre-viral entry and post-viral entry lifecycle stages, providing important insights for finding new approaches to treating hepatitis B.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Editorial Material
Gastroenterology & Hepatology
Y. U. S. U. K. E. Shimakawa, G. I. B. R. I. L. Ndow, A. T. S. U. S. H. Kaneko, K. A. T. S. U. M. Aoyagi, M. A. U. D. Lemoine, Y. A. S. U. H. I. T. O. Tanaka
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Michihiro Yoshida, Hiroshi Yukawa, Kazuki Hayashi, Itaru Naitoh, Katsuyuki Miyabe, Yasuki Hori, Makoto Natsume, Naruomi Jinno, Akihisa Kato, Kenta Kachi, Go Asano, Hidenori Sahashi, Tadashi Toyohara, Kayoko Kuno, Yusuke Kito, Hiromu Kondo, Atsuyuki Hirano, Fumihiro Okumura, Kaiki Anbe, Yoshinobu Baba, Hiromi Kataoka, Yasuhito Tanaka
Summary: This study investigates the potential biomarkers for biliary tract cancers (BTCs) through the analysis of exosomal microRNAs (miRNAs) in bile samples. The results suggest that several exosomal miRNAs in bile show aberrant expression, while no abnormal expression is found in serum samples. MiR-451a and miR-3619-3p are identified as reproducible upregulated markers in bile, and their combination can effectively diagnose BTCs.
Article
Gastroenterology & Hepatology
Korenobu Hayama, Masanori Atsukawa, Akihito Tsubota, Chisa Kondo, Motoh Iwasa, Hiroshi Hasegawa, Koichi Takaguchi, Akemi Tsutsui, Haruki Uojima, Hisashi Hidaka, Hironao Okubo, Tatsuya Suzuki, Kentaro Matsuura, Toshifumi Tada, Naoto Kawabe, Joji Tani, Asahiro Morishita, Toru Ishikawa, Yoshitaka Arase, Yoshihiro Furuichi, Keizo Kato, Kazuhito Kawata, Makoto Chuma, Akito Nozaki, Atsushi Hiraoka, Tsunamasa Watanabe, Tatehiro Kagawa, Hidenori Toyoda, Nobuhiko Taniai, Hiroshi Yoshida, Yasuhito Tanaka, Katsuhiko Iwakiri
Summary: This study aimed to evaluate the outcome in patients with portal vein thrombosis (PVT) who received antithrombin III-based therapy. The results showed that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for PVT patients.
HEPATOLOGY RESEARCH
(2023)
Editorial Material
Gastroenterology & Hepatology
Kotaro Waki, Kenshi Matsuno, Hideaki Miyamoto, Ryosuke Gushima, Hiroki Takeda, Yorihisa Orita, Yasuhito Tanaka
Article
Biochemistry & Molecular Biology
Go Sugahara, Yuji Ishida, Jae Jin Lee, Meng Li, Yasuhito Tanaka, Hyungjin Eoh, Yusuke Higuchi, Takeshi Saito
Summary: This study aimed to define the environmental requirements necessary for maintaining the homeostasis of terminally differentiated hepatocytes. The supplementation of dimethyl sulfoxide (DMSO) was found to be indispensable for mitigating fate deterioration and promoting adaptation to the in vitro environment. Dimethyl sulfone (DMSO2) was identified as a substitute for DMSO, supporting the long-term maintenance of hepatocyte morphology, marker gene expression, and functionality.
Article
Gastroenterology & Hepatology
Harry L. A. Janssen, Jinlin Hou, Tarik Asselah, Henry L. Y. Chan, Fabien Zoulim, Yasuhito Tanaka, Ewa Janczewska, Ronald G. Nahass, Stefan Bourgeois, Maria Buti, Pietro Lampertico, Oliver Lenz, Thierry Verbinnen, Joris Vandenbossche, Willem Talloen, Ronald Kalmeijer, Maria Beumont, Michael Biermer, Umesh Shukla
Summary: The study evaluated the efficacy and safety of JNJ-56136379 in patients with chronic hepatitis B. The results showed that JNJ-56136379+NA significantly reduced HBV DNA and HBV RNA levels, but had limited effects on HBsAg or HBeAg declines in HBeAg-positive patients. Overall, JNJ-56136379 did not demonstrate clear superiority over NA in terms of efficacy.
Article
Gastroenterology & Hepatology
Masanori Atsukawa, Akihito Tsubota, Chisa Kondo, Kaori-Shioda Koyano, Toru Ishikawa, Hidenori Toyoda, Koichi Takaguchi, Tsunamasa Watanabe, Kentaro Matsuura, Chikara Ogawa, Atsushi Hiraoka, Hironao Okubo, Masakuni Tateyama, Haruki Uojima, Akito Nozaki, Makoto Chuma, Keizo Kato, Shigeru Mikami, Joji Tani, Asahiro Morishita, Kazuhito Kawata, Toshifumi Tada, Yoshihiro Furuichi, Tomomi Okubo, Tadamichi Kawano, Taeang Arai, Naoto Kawabe, Naohiro Kawamura, Tadashi Ikegami, Makoto Nakamuta, Ryuta Shigefuku, Motoh Iwasa, Yasuhito Tanaka, Masaru Hatano, Katsuhiko Iwakiri
Summary: This study identified factors associated with a high TRPG in cirrhosis patients and developed a scoring model to identify those at high risk of PoPH, which can be used to select patients who may benefit from echocardiography investigations.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Takanori Suzuki, Kentaro Matsuura, Kenji Urakabe, Fumihiro Okumura, Hayato Kawamura, Satoshi Sobue, Sho Matoya, Tomokatsu Miyaki, Yoshihide Kimura, Daisuke Kato, Atsunori Kusakabe, Yoshito Tanaka, Atsushi Ozasa, Yoshihito Nagura, Kei Fujiwara, Shunsuke Nojiri, Shinya Hagiwara, Shigeru Kusumoto, Takako Inoue, Yasuhito Tanaka, Hiromi Kataoka
Summary: This retrospective study investigated the clinical outcomes of patients with nucleos(t)ide analogs (NAs) therapy for hepatitis B virus (HBV) reactivation prevention. The study showed that there may be a risk of viral relapse after cessation of NA therapy, but most patients had low levels of HBV DNA and no increase in alanine aminotransferase. Thus, proactive cessation of NA therapy may be considered if the primary disease is under remission, but careful follow-up is necessary after stopping NA therapy.
HEPATOLOGY RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Tatsuki Mizuochi, Itaru Iwama, Ayano Inui, Yoshinori Ito, Yugo Takaki, Sotaro Mushiake, Daisuke Tokuhara, Takashi Ishige, Koichi Ito, Jun Murakami, Haruka Hishiki, Hitoshi Mikami, Kazuhiko Bessho, Ken Kato, Ryosuke Yasuda, Yushiro Yamashita, Yasuhito Tanaka, Hitoshi Tajiri
Summary: This study assessed the real-world efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese adolescents with chronic hepatitis C virus (HCV). The results showed that G/P treatment was highly efficacious and well tolerated, with all patients achieving sustained virologic response at 12 weeks after treatment completion.
JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Virology
Yuki Takamatsu, Sanae Hayashi, Hiroki Kumamoto, Shuhei Imoto, Yasuhito Tanaka, Hiroaki Mitsuya, Nobuyo Higashi-Kuwata
Summary: This study investigated the effects of chronic HBV infection on cellular senescence in human hepatocytes and humanized-liver chimeric mice. The results showed that HBV infection perturbed multiple senescence-associated markers in both human hepatocytes and humanized-mice liver, while treatment with the anti-HBV drug E-CFCP restored this phenomenon.
Article
Oncology
Takayuki Tokunaga, Masakuni Tateyama, Yasuteru Kondo, Satoshi Miuma, Shiho Miyase, Kentaro Tanaka, Satoshi Narahara, Hiroki Inada, Sotaro Kurano, Yoko Yoshimaru, Katsuya Nagaoka, Takehisa Watanabe, Hiroko Setoyama, Kotaro Fukubayashi, Motohiko Tanaka, Yasuhito Tanaka
Summary: This study aimed to evaluate the impact of therapeutic modifications of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (uHCC). Patients with therapeutic modifications other than discontinuation of both drugs had favorable overall survival and time to progression, while those with discontinuation of both drugs had unfavorable outcomes. Modified liver function and immune-related adverse events increased the risk of discontinuation without other therapeutic modifications. Avoiding discontinuation without other therapeutic modifications may be the optimal management for uHCC.
Article
Medicine, Research & Experimental
Takeshi Chida, Yuji Ishida, Sho Morioka, Go Sugahara, Christine Han, Bill Lam, Chihiro Yamasaki, Remi Sugahara, Meng Li, Yasuhito Tanaka, T. Jake Liang, Chise Tateno, Takeshi Saito
Summary: Hepatitis delta virus (HDV), a satellite virus of HBV, induces a potent and persistent activation of the IFN system in human hepatocytes, while HBV is not capable of triggering a hepatic antiviral response. HDV's constitutive activation of the hepatic IFN system suppresses HBV but modestly inhibits HDV, creating a paradoxical mode of viral interference. Furthermore, the study reveals that HDV-induced constitutive IFN system activation leads to IFN refractoriness, rendering therapeutic IFNs ineffective.
Article
Gastroenterology & Hepatology
Hiroko Setoyama, Nao Nishida, Shintaro Nagashima, Ko Ko, Taiji Yamazoe, Yasuhito Tanaka, Masashi Mizokami, Junko Tanaka, Tatsuya Kanto
Summary: This study aimed to establish a reliable host genome analysis technique for countries with inadequate infrastructure, and found associations between HLA-DPB1 and hepatitis B in the Cambodian population.
HEPATOLOGY RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Hiroki Kumamoto, Nobuyo Higashi-Kuwata, Sanae Hayashi, Debananda Das, Haydar Bulut, Ryoh Tokuda, Shuhei Imoto, Kengo Onitsuka, Yuka Honda, Yuki Odanaka, Satoko Shimbara-Matsubayashi, Kazuhiro Haraguchi, Yasuhito Tanaka, Hiroaki Mitsuya
Summary: Encouraged by previous findings, we designed and synthesized compound 6 as a hybrid of potent anti-HBV agents 4 and 5. The stereospecific construction of the chiral quaternary carbon portion was achieved through radical-mediated cyclization. The introduction of a fluorine atom was accomplished through stannylation and electrophilic fluorination. Compound (E)-6 displayed highly potent anti-HBV activity and favorable cytotoxicity.
Article
Gastroenterology & Hepatology
Kenshi Matsuno, Hideaki Miyamoto, Hideki Kitada, Shinichi Yoshimatsu, Fumio Tamura, Kouichi Sakurai, Kotaro Fukubayashi, Takashi Shono, Hiroko Setoyama, Taichi Matsuyama, Shinichiro Suko, Rei Narita, Munenori Honda, Masakuni Tateyama, Hideaki Naoe, Jun Morinaga, Yasuhito Tanaka, Ryosuke Gushima
Summary: This study compared the efficacy of endoscopic submucosal resection with band ligation (ESMR-L) and endoscopic submucosal dissection (ESD) in the treatment of small rectal neuroendocrine tumors (NETs). The results showed that both methods had similar high complete resection rates, but ESMR-L had shorter procedure time and hospitalization period, making it a more efficient treatment method, especially for less-experienced endoscopists.