PMID- 29094205
OWN - NLM
STAT- In-Data-Review
LR  - 20180531
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Linking)
VI  - 53
IP  - 6
DP  - 2018 Jun
TI  - Association between alanine aminotransferase elevation and UGT1A1*6 polymorphisms
      in daclatasvir and asunaprevir combination therapy for chronic hepatitis C.
PG  - 780-786
LID - 10.1007/s00535-017-1405-3 [doi]
AB  - BACKGROUND: Liver damage presented as alanine aminotransferase (ALT) elevation
      and high ALT-caused treatment discontinuation occurs with high frequency in
      Japanese patients receiving daclatasvir plus asunaprevir (DCV/ASV) therapy for
      hepatitis C virus (HCV) infection, and its mechanism is unknown. METHODS: A total
      of 247 Japanese patients consisting of two independent cohorts with genotype-1b
      HCV infection receiving DCV/ASV therapy were included. The association of ALT
      levels during therapy and single nucleotide polymorphisms (SNP) of five
      drug-metabolizing enzyme loci selected for their possible influence on NS3/4A and
      NS5A inhibitors was investigated. RESULTS: Among five SNPs, we found a
      significant correlation between the presence of the UGT1A1 rs4148323 A allele and
      ALT elevation (Grade 3 elevation in AA 57%, AG 18%, and GG 4%, P = 8.4E - 06) and
      drug discontinuation (AA 22%, AG 11%, and GG 2.5%, P = 8.7E - 04), while no
      association was observed with ALT values at baseline (Grade 3 elevation AA 0%, AG
      4%, and GG 2%, P = 0.5). In contrast, patients with risk A allele for
      drug-induced ALT elevation had a tendency to respond more favorably to treatment 
      (AA 100%, AG 93%, and GG 90%, P = 0.29). CONCLUSIONS: Through the analysis we
      suggest that the A allele in UGT1A1 rs4148323 (UGT1A1*6), which is highly
      prevalent in the Japanese population, should be considered a risk for the
      development of DCV/ASV therapy-induced ALT elevation. Pretreatment SNP testing of
      UGT1A1*6 might be beneficial for the prediction of liver damage induced by
      DCV/ASV or even by DCV/ASV plus beclabuvir.
FAU - Maekawa, Shinya
AU  - Maekawa S
AUID- ORCID: http://orcid.org/0000-0002-5643-9472
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
      maekawa@yamanashi.ac.jp.
FAU - Sato, Mitsuaki
AU  - Sato M
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Kuratomi, Natsuhiko
AU  - Kuratomi N
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Inoue, Taisuke
AU  - Inoue T
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Suzuki, Yuichiro
AU  - Suzuki Y
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Tatsumi, Akihisa
AU  - Tatsumi A
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Miura, Mika
AU  - Miura M
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Matsuda, Shuya
AU  - Matsuda S
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Muraoka, Masaru
AU  - Muraoka M
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Nakakuki, Natsuko
AU  - Nakakuki N
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Amemiya, Fumitake
AU  - Amemiya F
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Takano, Shinichi
AU  - Takano S
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Fukasawa, Mitsuharu
AU  - Fukasawa M
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Nakayama, Yasuhiro
AU  - Nakayama Y
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Yamaguchi, Tatsuya
AU  - Yamaguchi T
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Sato, Tadashi
AU  - Sato T
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Sakamoto, Minoru
AU  - Sakamoto M
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
FAU - Murakawa, Miyako
AU  - Murakawa M
AD  - Department of Gastroenterology and Hepatology, Tokyo Medical and Dental
      University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
FAU - Nakagawa, Mina
AU  - Nakagawa M
AD  - Department of Gastroenterology and Hepatology, Tokyo Medical and Dental
      University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
FAU - Asahina, Yasuhiro
AU  - Asahina Y
AD  - Department of Gastroenterology and Hepatology, Tokyo Medical and Dental
      University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
FAU - Enomoto, Nobuyuki
AU  - Enomoto N
AD  - First Department of Internal Medicine, Faculty of Medicine, University of
      Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
LA  - eng
GR  - 16fK0210301h0003/Japan Agency for Medical Research and Development
GR  - 16fk0210102h0001/Japan Agency for Medical Research and Development
GR  - 16fK0210308h0003/Japan Agency for Medical Research and Development
GR  - 16K09349/Japan Society for the Promotion of Science
PT  - Journal Article
DEP - 20171101
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
OTO - NOTNLM
OT  - ALT elevation
OT  - DCV/ASV therapy
OT  - HCV
OT  - UGT1A1*6 SNP
EDAT- 2017/11/03 06:00
MHDA- 2017/11/03 06:00
CRDT- 2017/11/03 06:00
PHST- 2017/07/07 00:00 [received]
PHST- 2017/10/20 00:00 [accepted]
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2017/11/03 06:00 [entrez]
AID - 10.1007/s00535-017-1405-3 [doi]
AID - 10.1007/s00535-017-1405-3 [pii]
PST - ppublish
SO  - J Gastroenterol. 2018 Jun;53(6):780-786. doi: 10.1007/s00535-017-1405-3. Epub
      2017 Nov 1.