Evidence map›Paper›PMID 29094205›Full record

ArticleJournal of gastroenterology2018

Association between alanine aminotransferase elevation and UGT1A1*6 polymorphisms in daclatasvir and asunaprevir combination therapy for chronic hepatitis C.

Shinya Maekawa, Mitsuaki Sato, Natsuhiko Kuratomi, Taisuke Inoue, Yuichiro Suzuki, Akihisa Tatsumi, Mika Miura, Shuya Matsuda, Masaru Muraoka, Natsuko Nakakuki and 11 more

Abstract read
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In one paragraph

Article in Journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Observational
  5. Article
  6. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 1 country.

Shinya MaekawaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. maekawa@yamanashi.ac.jp.ORCID http://orcid.org/0000-0002-5643-9472
Mitsuaki SatoFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Natsuhiko KuratomiFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Taisuke InoueFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Yuichiro SuzukiFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Akihisa TatsumiFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Mika MiuraFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Shuya MatsudaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Masaru MuraokaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Natsuko NakakukiFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Fumitake AmemiyaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Shinichi TakanoFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Mitsuharu FukasawaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Yasuhiro NakayamaFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Tatsuya YamaguchiFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Tadashi SatoFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Minoru SakamotoFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Miyako MurakawaDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
Mina NakagawaDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
Yasuhiro AsahinaDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo, 113-0034, Japan.
Nobuyuki EnomotoFirst Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
University of Yamanashi Hospital · JPTokyo Medical and Dental University · JP

Funding

Japan Agency for Medical Research and Development 16fk0210102h0001Japan Agency for Medical Research and Development 16fK0210301h0003Japan Agency for Medical Research and Development 16fK0210308h0003Japan Society for the Promotion of Science 16K09349
6 · The paper itself

Abstract

backgroundLiver 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.

methodsA 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.

resultsAmong 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).

conclusionsThrough 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.

Indexed as

Polymorphism, Single NucleotideAdultAgedAged, 80 and overAlanine TransaminaseAntiviral AgentsBiomarkersCarbamatesChemical and Drug Induced Liver InjuryDrug Therapy, CombinationFemaleGenetic Predisposition to DiseaseGlucuronosyltransferaseHepatitis C, ChronicHumansImidazolesAlanine TransaminaseAntiviral AgentsasunaprevirBiomarkersCarbamatesdaclatasvirGlucuronosyltransferaseImidazolesIsoquinolinesPyrrolidinesSulfonamidesUGT1A1 EnzymeValineALT elevationDCV/ASV therapyHCVUGT1A1*6 SNP

Identifiers

PMID29094205
OpenAlexW2766856516

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.