PMID- 36583370
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230430
IS  - 1386-6346 (Print)
IS  - 1386-6346 (Linking)
VI  - 53
IP  - 5
DP  - 2023 May
TI  - Significant association between HLA-B*35:01 and onset of drug-induced liver 
      injury caused by Kampo medicines in Japanese patients.
PG  - 440-449
LID - 10.1111/hepr.13874 [doi]
AB  - AIM: Drug-induced liver injury (DILI) is a severe and life-threatening 
      immune-mediated adverse effect, occurring rarely among treated patients. We 
      examined genomic biomarkers in the Japanese population that predict the onset of 
      DILI after using a certain class of drugs, such as Kampo products (Japanese 
      traditional medicines). METHODS: A total of 287 patients diagnosed as DILI by 
      hepatology specialists were recruited after written informed consent was 
      obtained. A genome-wide association analysis and human leukocyte antigen (HLA) 
      typing in four digits were performed. RESULTS: We found a significant association 
      (p = 9.41 x 10(-10) ) of rs146644517 (G > A) with Kampo product-related DILI. As 
      this polymorphism is located in the HLA region, we evaluated the association of 
      HLA types and found that 12 (63.2%) of 19 Kampo-DILI patients contained 
      HLA-B*35:01, whereas only 15.2% were positive for this HLA among healthy 
      volunteers. The odds ratio was 9.56 (95% confidence interval 3.75-24.46; 
      p = 2.98 x 10(-6) , corrected p = 4.17 x 10(-5) ), and it increased to 13.55 
      compared with the DILI patients not exposed to Kampo products. The individual 
      crude drug components in the Kampo products, including Scutellaria root (ougon in 
      Japanese), rhubarb (daiou), Gardenia fruit (sanshishi), and Glycyrrhiza (kanzou), 
      were significantly associated with HLA-B*35:01. CONCLUSIONS: HLA-B*35:01 is a 
      genetic risk factor and a potential predictive biomarker for Kampo-induced DILI 
      in the Japanese population.
CI  - (c) 2022 Japan Society of Hepatology.
FAU - Nakamura, Ryosuke
AU  - Nakamura R
AUID- ORCID: 0000-0002-7756-3798
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Kawasaki, Japan.
FAU - Arakawa, Noriaki
AU  - Arakawa N
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Kawasaki, Japan.
FAU - Tanaka, Yoichi
AU  - Tanaka Y
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Kawasaki, Japan.
FAU - Uchiyama, Nahoko
AU  - Uchiyama N
AD  - Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of 
      Health Sciences, Kawasaki, Japan.
FAU - Sekine, Akihiro
AU  - Sekine A
AD  - Department of Infection and Host Defense, Chiba University Graduate School of 
      Medicine, Chiba, Japan.
FAU - Mashimo, Yoichi
AU  - Mashimo Y
AD  - Department of Public Health, Chiba University Graduate School of Medicine, Chiba, 
      Japan.
FAU - Tsuji, Keiji
AU  - Tsuji K
AD  - Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic Survivors 
      Hospital, Hiroshima, Japan.
FAU - Kagawa, Tatehiro
AU  - Kagawa T
AD  - Division of Gastroenterology, Department of Internal Medicine, Tokai University 
      School of Medicine, Isehara, Japan.
FAU - Sato, Ken
AU  - Sato K
AUID- ORCID: 0000-0002-3202-7983
AD  - Department of Gastroenterology and Hepatology, Gunma University Graduate School 
      of Medicine, Maebashi, Japan.
FAU - Watanabe, Masaaki
AU  - Watanabe M
AD  - Department of Gastroenterology, Kitasato University Medical Center, Kitamoto, 
      Japan.
FAU - Aiso, Mitsuhiko
AU  - Aiso M
AD  - Department of Medicine, Higashisaitama National Hospital, Hasuda, Japan.
FAU - Hiasa, Yoichi
AU  - Hiasa Y
AUID- ORCID: 0000-0003-4117-339X
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Toon, Japan.
FAU - Takei, Yoshiyuki
AU  - Takei Y
AD  - Department of Gastroenterology, Mie University, Tsu, Japan.
FAU - Ohira, Hiromasa
AU  - Ohira H
AD  - Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan.
FAU - Ayada, Minoru
AU  - Ayada M
AD  - Department of Internal Medicine, Kakegawa Higashi Hospital, Kakegawa, Japan.
FAU - Tsukagoshi, Eri
AU  - Tsukagoshi E
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Kawasaki, Japan.
FAU - Maekawa, Keiko
AU  - Maekawa K
AD  - Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, 
      Kyotanabe, Japan.
FAU - Tohkin, Masahiro
AU  - Tohkin M
AD  - Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 
      Japan.
FAU - Saito, Yoshiro
AU  - Saito Y
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Kawasaki, Japan.
FAU - Takikawa, Hajime
AU  - Takikawa H
AD  - Faculty of Medical Technology, Teikyo University, Tokyo, Japan.
LA  - eng
GR  - Ministry of Health, Labor, and Welfare/
PT  - Journal Article
DEP - 20230114
PL  - Netherlands
TA  - Hepatol Res
JT  - Hepatology research : the official journal of the Japan Society of Hepatology
JID - 9711801
OTO - NOTNLM
OT  - Kampo medicines
OT  - crude drug
OT  - drug-induced liver injury
OT  - genome-wide association study
OT  - human leukocyte antigen
EDAT- 2022/12/31 06:00
MHDA- 2022/12/31 06:01
CRDT- 2022/12/30 04:32
PHST- 2022/12/05 00:00 [revised]
PHST- 2022/08/02 00:00 [received]
PHST- 2022/12/24 00:00 [accepted]
PHST- 2022/12/31 06:01 [medline]
PHST- 2022/12/31 06:00 [pubmed]
PHST- 2022/12/30 04:32 [entrez]
AID - 10.1111/hepr.13874 [doi]
PST - ppublish
SO  - Hepatol Res. 2023 May;53(5):440-449. doi: 10.1111/hepr.13874. Epub 2023 Jan 14.