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Article

Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study

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Division of Medical Safety Science, National Institute of Health Sciences, Kanagawa 210-9501, Japan
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan
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Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima 730-8619, Japan
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Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
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Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
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Department of Gastroenterology, Fukuoka University Faculty of Medicine, Fukuoka 814-0180, Japan
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Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8648, Japan
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Department of Medicine, Teikyo University School of Medicine, Tokyo 173-8606, Japan
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Daiichi Sankyo Co., Ltd., Tokyo 134-8630, Japan
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Astellas Pharma Inc., Tsukuba 305-8585, Japan
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Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan
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Kihara Memorial Foundation, Yokohama 230-0045, Japan
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Faculty of Medical Technology, Teikyo University, Tokyo 173-8606, Japan
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(9), 355; https://doi.org/10.3390/metabo10090355
Received: 16 July 2020 / Revised: 26 August 2020 / Accepted: 28 August 2020 / Published: 31 August 2020
(This article belongs to the Special Issue Advances in Lipidomics: Biomedicine, Nutrients and Methodology)
Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers. We identified 463 lipids and compared their levels between the acute and recovery phases of the three types of DILI patients. Mixed and cholestatic types demonstrated specific plasma lipid alterations between the phases, but the hepatocellular type did not. Moreover, as specific indicators of mixed-type DILI, levels of several ceramides increased in the acute phase, while those of arachidonic acid-containing ether-linked phosphoglycerolipids decreased. In contrast, as specific indicators of cholestatic-type DILI, levels of palmitic acid-containing saturated or monounsaturated phosphatidylcholines increased in the acute phase, while those of arachidonic acid- or docosahexaenoic acid-containing ether-linked phosphoglycerolipids and phosphatidylinositols decreased. We also identified lipids with a relatively high capacity to discriminate the acute phase from the recovery phase and healthy subjects. These findings may help with understanding the pathophysiology of different DILI types and identify candidate biomarkers. View Full-Text
Keywords: lipidomics; drug-induced liver injury; biomarker; plasma lipid profiles lipidomics; drug-induced liver injury; biomarker; plasma lipid profiles
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MDPI and ACS Style

Saito, K.; Kagawa, T.; Tsuji, K.; Kumagai, Y.; Sato, K.; Sakisaka, S.; Sakamoto, N.; Aiso, M.; Hirose, S.; Mori, N.; Tanaka, R.; Uraoka, T.; Takata, K.; Ogawa, K.; Mori, K.; Sato, M.; Nishiya, T.; Takamatsu, K.; Arakawa, N.; Izumi, T.; Ohno, Y.; Saito, Y.; Takikawa, H. Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study. Metabolites 2020, 10, 355. https://doi.org/10.3390/metabo10090355

AMA Style

Saito K, Kagawa T, Tsuji K, Kumagai Y, Sato K, Sakisaka S, Sakamoto N, Aiso M, Hirose S, Mori N, Tanaka R, Uraoka T, Takata K, Ogawa K, Mori K, Sato M, Nishiya T, Takamatsu K, Arakawa N, Izumi T, Ohno Y, Saito Y, Takikawa H. Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study. Metabolites. 2020; 10(9):355. https://doi.org/10.3390/metabo10090355

Chicago/Turabian Style

Saito, Kosuke, Tatehiro Kagawa, Keiji Tsuji, Yuji Kumagai, Ken Sato, Shotaro Sakisaka, Naoya Sakamoto, Mitsuhiko Aiso, Shunji Hirose, Nami Mori, Rieko Tanaka, Toshio Uraoka, Kazuhide Takata, Koji Ogawa, Kazuhiko Mori, Motonobu Sato, Takayoshi Nishiya, Kazuhiko Takamatsu, Noriaki Arakawa, Takashi Izumi, Yasuo Ohno, Yoshiro Saito, and Hajime Takikawa. 2020. "Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study" Metabolites 10, no. 9: 355. https://doi.org/10.3390/metabo10090355

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