Evidence map›Paper›PMID 27776192›Full record

ArticlePloS one2016

Complex Pattern of Resistance-Associated Substitutions of Hepatitis C Virus after Daclatasvir/Asunaprevir Treatment Failure.

Jun Itakura, Masayuki Kurosaki, Chitomi Hasebe, Yukio Osaki, Kouji Joko, Hitoshi Yagisawa, Shinya Sakita, Hiroaki Okushin, Takashi Satou, Hiroyuki Hisai and 13 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

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  18. Real-world safety and efficacy of sofosbuvir and ledipasvir for elderly patients.JGH open : an open access journal of gastroenterology and hepatology · 2018
    Article
  19. Article
  20. Use of a hepatitis C virus (HCV) RNA-positive donor in a treated HCV RNA-negative liver transplant recipient.Transplant infectious disease : an official journal of the Transplantation Society · 2018
    Article
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

23 authors.

Jun ItakuraDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Masayuki KurosakiDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Chitomi HasebeDepartment of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Hokkaido, Japan.
Yukio OsakiDepartment of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Osaka, Japan.
Kouji JokoCenter for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
Hitoshi YagisawaDepartment of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Akita, Japan.
Shinya SakitaDepartment of Gastroenterology, Yokohama City Minato Red Cross Hospital, Yokohama, Kanagawa, Japan.
Hiroaki OkushinDepartment of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan.
Takashi SatouDepartment of Gastroenterology, Nasu Red Cross Hospital, Otawara, Tochigi, Japan.
Hiroyuki HisaiDepartment of Gastroenterology, Date Red Cross Hospital, Date, Hokkaido, Japan.
Takehiko AbeDepartment of Gastroenterology, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
Keiji TsujiDepartment of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Hiroshima, Japan.
Takashi TamadaDepartment of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan.
Haruhiko KobashiDepartment of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Okayama, Japan.
Akeri MitsudaDepartment of Gastroenterology, Japanese Red Cross Tottori Hospital, Tottori, Tottori, Japan.
Yasushi IdeDepartment of Gastroenterology, Japanese Red Cross Karatsu Hospital, Karatsu, Saga, Japan.
Chikara OgawaDepartment of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan.
Syotaro TsurutaDepartment of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Nagasaki, Japan.
Kouichi TakaguchiDepartment of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan.
Miyako MurakawaDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan.
Yasuhiro AsahinaDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan.
Nobuyuki EnomotoFirst Department of Internal Medicine, University of Yamanashi, Chuou, Yamanashi, Japan.
Namiki IzumiDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUNDS &

aimsWe aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection.

methodsThis is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing.

resultsThe frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients.

conclusionTreatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors.

Indexed as

AgedCarbamatesDrug Therapy, CombinationFemaleHepacivirusHepatitis C, ChronicHumansImidazolesIsoquinolinesMaleMiddle AgedPyrrolidinesSulfonamidesTreatment OutcomeValineasunaprevirCarbamatesdaclatasvirImidazolesIsoquinolinesPyrrolidinesSulfonamidesValine

Identifiers

PMID27776192
PMCPMC5077083

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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.