Evidence map›Paper›PMID 31291311›Full record

ArticlePloS one2019

Single nucleotide polymorphisms associated with elevated alanine aminotransferase in patients receiving asunaprevir plus daclatasvir combination therapy for chronic hepatitis C.

Keizo Kato, Noritomo Shimada, Masanori Atsukawa, Hiroshi Abe, Norio Itokawa, Yoshihiro Matsumoto, Rie Agata, Akihito Tsubota

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.1field-weighted citation impact, top 49% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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

8 authors at 4 institutions in 1 country.

Keizo KatoLiver Disease Control Science, Graduate School of Organic Pathology and Therapeutics, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.ORCID 0000-0003-2184-6016
Noritomo ShimadaDivision of Gastroenterology and Hepatology, Ootakanomori Hospital, Kashiwa, Chiba, Japan.
Masanori AtsukawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
Hiroshi AbeDivision of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan.
Norio ItokawaDivision of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
Yoshihiro MatsumotoDivision of Gastroenterology and Hepatology, The Jikei University School of Medicine, Kashiwa Hospital, Chiba, Japan.
Rie AgataCore Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
Akihito TsubotaLiver Disease Control Science, Graduate School of Organic Pathology and Therapeutics, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.ORCID 0000-0001-6860-0326
Jikei University School of Medicine · JPChiba Hokusou Hospital · JPNippon Medical School · JPShinmatsudo Central General Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsDrug-induced liver damage characterized by serum alanine aminotransferase (ALT) elevation often occurs in direct-acting antiviral (DAA) combination therapy for chronic hepatitis C virus (HCV) infection. This study explored single nucleotide polymorphisms (SNPs) at drug metabolism- or transport-related genes that were associated with ALT elevation in asunaprevir plus daclatasvir therapy.

methodsSubjects were 185 Japanese patients with chronic HCV genotype 1b infection who received asunaprevir plus daclatasvir therapy. Tag SNPs at possible metabolizing enzyme and transporter genes, which were involved in the pharmacokinetics of asunaprevir and daclatasvir, were selected.

resultsAmong the tag SNPs analyzed, CYP3A4 rs4646437 was significantly associated with ALT elevation (p = 0.013): maximum ALT values in patients with genotype CC were higher than those in patients with genotype non-CC (allele T). The proportion of grades 2-4 in genotype CC patients were significantly greater than those in genotype non-CC patients (p = 0.028). No patients with genotype non-CC showed grade ≥2 ALT elevation. In multivariate analysis, rs4646437 genotype CC and cirrhosis were significant, independent factors associated with grade ≥1 ALT elevation (odds ratio, 2.83 and 1.88; p = 0.040 and 0.045, respectively). In exploratory analyses, although serum concentrations of asunaprevir and daclatasvir were not correlated with maximum ALT values or rs4646437 genotypes, asunaprevir concentrations in patients with grade ≥1 ALT elevation were significantly higher than those in patients with grade <1 ALT elevation (P = 0.023).

conclusionsCYP3A4 rs4646437 was found to be significantly and independently associated with ALT elevation in Japanese patients receiving ASV plus DCV therapy. Notably, none of the patients with rs4646437 genotype non-CC (allele T) had grade ≥2 ALT elevation. SNP genotyping prior to treatment might be useful for carefully monitoring patients to complete treatment safely.

Indexed as

AdultAgedAged, 80 and overAlanine TransaminaseCarbamatesChemical and Drug Induced Liver InjuryCytochrome P-450 CYP3ADrug Therapy, CombinationFemaleGenotypeHepacivirusHepatitis C, ChronicHumansImidazolesIsoquinolinesJapanAlanine TransaminaseasunaprevirCarbamatesCYP3A protein, humanCytochrome P-450 CYP3AdaclatasvirImidazolesIsoquinolinesPyrrolidinesSulfonamidesValine

Identifiers

PMID31291311
PMCPMC6619746
OpenAlexW2958393899

What OpenQuestion holds

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LicenceCC BY
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.