Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Tuesday, 03 / 09 / 2021

Welcome to JCTH

ORIGINAL ARTICLE

A 3D Human Liver Model of Nonalcoholic Steatohepatitis

Marion Duriez1, Agnes Jacquet1Lucile Hoet1Sandrine Roche1Marie-Dominique Bock1Corinne Rocher1Gilles Haussy1Xavier Vigé1Zsolt Bocskei1 Tamara Slavnic2 Valérie Martin3Jean-Claude Guillemot1Michel Didier1Aimo Kannt4,5Cécile Orsini, Vincent Mikol1 and Anne-Céline Le Fèvre*,1

1  Translational Sciences, Sanofi, 1 Avenue Pierre Brossolette, Chilly-Mazarin, France
2  IT&M STATS, Groupe IT&M, Neuilly-sur-Seine, France
3  Non Clinical Biostatistics, Sanofi, Vitry sur Seine, France
4  Diabetes and Cardiovascular Research, Sanofi, Industriepark Höchst, Frankfurt, Germany
5  Present address: Institute of Experimental Pharmacology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
*Correspondence to: Anne-Céline Le Fèvre, Translational Sciences, Sanofi, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France. Tel: +33-160495815, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2020;8(4):359-370 DOI: 10.14218/JCTH.2020.00015
Received: March 2, 2020 Accepted: June 1, 2020 Published online: December 15, 2020

Abstract

Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the development of an in vitro 3D model to mimic liver architecture and the NASH environment.

Methods: We have developed an in vitro preclinical 3D NASH model by coculturing primary human hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by addition of medium containing free fatty acids and tumor necrosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses.

Results: We succeeded in defining suitable culture conditions to maintain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom medium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induction.

Conclusions: This is a new in vitro model of NASH disease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.

Keywords

3D liver model, Human primary cells, Key features of NASH

Journal of Clinical and Translational Hepatology 2020 vol. 8, 359-370  [ Html  ] [ PDF Full-text ]

© The Authors 2020. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

EDITORIAL

Journal of Clinical and Translational Hepatology Has Been Indexed in SCIE: A Milestone towards a Greater Academic Goal

Harry Hua-Xiang Xia, George Y. Wu2 Hong Ren*,3

1  Department of Gastroenterology, First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
2  Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
3  Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
*Correspondence to: Hong Ren, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2020;8(4):357-358 DOI: 10.14218/JCTH.2020.00138
Received: December 2, 2020 Accepted: December 13, 2020 Published online: December 26, 2020

 

On November 10, 2020, the Editorial Office received a notification letter from Clarivate Analytics stating that Journal of Clinical and Translational Hepatology (JCTH) had been selected to be included in citation indexes in the Web of Science, and that articles published in JCTH after December 30, 2017 will be listed in some of the most influential and widely used databases in the world, including Current Contents/Clinical Medicine, Science Citation Index Expanded (SCIE), Essential Science Indicators, and Journal Citation Reports Science.

While indexing in the major databases, including PubMed/PubMed Central in 2015, Emerging Science Citation Resources in 2018 and Scopus in early 2020, was testimony to the excellence of JCTH, there was no assurance that the Journal would be accepted by the most exclusive of indices. We — Prof. Hong Ren, the General Editor-in-Chief; Prof. George Y. Wu, Comprehensive Editor-in-Chief; and Dr. Harry Hua-Xiang Xia, Co-Editor-in-Chief — have attempted to provide strategic vision, effective leadership, and stringent ethical standards for the Journal. But, all of this would have been of little consequence had it not been for the tremendous contributions of the associate editors, editorial board members, reviewers, authors, and staff of the editorial office. It is primarily because of their collective efforts that JCTH has achieved worldwide recognition in the competitive environment of academic publishing. Therefore, we, on behalf of the Journal, wish to take this opportunity to thank all of those individuals who have worked so hard and done so well to date.

On this momentous occasion, it is fitting to review the history of JCTH and the journey that led to its current status. The initiation and preparation for the creation of the Journal began in the Spring of 2010, when Dr. Xia was told by Dr. Qingfeng Sun from The Third Affiliated Hospital to Wenzhou Medical University that Prof. Ren, the Editor-in-Chief of a prestigious Chinese journal named Chinese Journal of Hepatology, intended to launch an English language journal in hepatology for The Second Affiliated Hospital of Chongqing Medical University, China. He approached Prof. Dazhi Zhang, Director of the Editorial Office of Chinese Journal of Hepatology, and the two had a very productive conversation. After several rounds of teleconferences and personal meetings in Xiamen, Chongqing, and Guangzhou, a general consensus was achieved that the project was worthwhile and feasible.

Xia & He Publishing Limited was engaged to undertake the task. Xia & He Publishing Limited had been originally registered since July 29, 2011 in Hong Kong, and was later established as Xia & He Publishing Inc. on January 8, 2015 in the USA under the very capable management of Dr. Hua He. The contract for publishing JCTH was signed by Prof. Ren and Dr. Xia on November 29 and December 8, 2011, respectively. In the meantime, Dr. Xia cordially invited Prof. Wu to be the Comprehensive Editor-in-Chief, owing to his remarkable academic record and international reputation. Dr. Xia and Prof. Wu, along with his wife, Prof. Catherine Wu, first met on November 27, 2010. In that and subsequent meetings and relaxed conversations — of course, over lunch at Chinese restaurants — numerous common views and perspectives were shared on the proposed journal.

After more than 2 years of preparation, JCTH was officially launched in September 2013, with an initial issue that featured an editorial entitled “Found in Translation” by Prof. Wu.1 Since then, JCTH has published quarterly, yielding 29 issues with 361 peer-reviewed articles as of November 10, 2020. Of these articles, 92.0% are original and review articles, and 54.6% have been financially supported from various research funding sources, with The National Institutes of Health and National Natural Science Foundation of China listed as sponsors of the research in 24.9% of the articles. From the outset, JCTH sought to be diverse, international, and inclusive in both its articles and review panels; for the latter, the success of this approach is reflected by the composition of the Editorial Board, which now consists of 143 experts from 23 countries and regions, with 37.1% from China and 32.2% from the USA, followed by Egypt, India, Italy, etc. The corresponding authors of the articles published in JCTH to date are from 32 countries and regions, with 35.5% of them from the USA and 23.0% from China, followed by India, Egypt, Italy, etc. The reviewers are from 40 countries and regions, with 24.8% of them from the USA and 19.2% from China, followed by Japan, India, Italy, etc.

According to the Web of Science, as of November 10, 2020, the most cited JCTH article has been referenced 205 times,2 and one of the articles on COVID-19 published in the early 2020 has already been cited 56 times.3 The readership interest in and academic influence of JCTH have also been reflected by estimated unofficial impact factors for 2017, 2018 and 2019 of 3.615, 3.489 and 4.546, respectively, with a self-citation rate of only 1.4%. In June 2021, JCTH will receive its first official impact factor, which is expected to be around 3.5.

While indexing in SCIE is a major achievement and a remarkable milestone for JCTH, it is obviously not the final goal. As stated in our inaugural issue, “the objective of the Journal of Clinical and Translational Hepatology is to identify and publish articles that represent translations of fundamental research to contributions of direct practical value”.1 In all that JCTH does, this is and will remain the fundamental and paramount mission. That objective is also symbolized in our logo, in which translational research promotes the proper placement of pieces of a puzzle to form an ever more accurate picture of the liver. However, in the pursuit of this objective, we are planning to further increase the international influence of JCTH by inviting more high-profile experts to the editorial board and further increasing the standards for manuscripts to be published in the Journal. Within the next 10 years, we will strive for the Journal to become listed among the top 25% of journals in gastroenterology and hepatology, according to the Web of Science Journal Citation Reports.

In closing, we wish to share reflections that encapsulate the vision for the future of JCTH as composed by Dr. Xia in Chinese, with English translation in parentheses:

同谋肝胆志,

共表中华情.

十年磨一剑,

携手启新程.

(With a graceful ambition and careful preparation,

We determined to launch an internationally influential hepatology journal in China.

With such a major milestone met after 10 years of persistence and endeavor,

We start a new journey toward a greater goal together.)

 

Journal of Clinical and Translational Hepatology 2020 vol. 8, 357-358  [ Html  ] [ PDF Full-text ]

© The Authors 2020. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

ORIGINAL ARTICLE

Association of TCF7L2 rs7903146 Gene Polymorphism with the Risk of NAFLD and CAD in the Chinese Han Population

Xin Yan1,4 , Wenwen Jin1 Jie Zhang1 Mengke Wang1, Shousheng Liu*,2,3 and Yongning Xin*,1,2,3

1  Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
2  Clinical Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China
3  Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
4  Dalian Medical University, Dalian, Liaoning, China
*Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; Shousheng Liu, Clinical Research Center, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-88905831, Fax: +86-532-88905293, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2020;8(4):371-376 DOI: 10.14218/JCTH.2020.00071
ReceivedJuly 26, 2020 Accepted: September 24, 2020 Published online: October 14, 2020

Abstract

Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population.

Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0.

Results: There were no significant differences in the distributions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041).

Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.

Keywords

Nonalcoholic fatty liver disease, Coronary artery disease, TCF7L2, Single nucleotide polymorphism

Journal of Clinical and Translational Hepatology 2020 vol. 8, 371-376  [ Html  ] [ PDF Full-text ]

© The Authors 2020. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

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