Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

Altunok, Elif Sargın; Sayan, Murat; Akhan, Sıla; Aygen, Bilgehan; Yıldız, Orhan; Koruk, Süda Tekin; Mıstık, Reşit; Demirtürk, Neşe; Ural, Onur; Köse, Şükran; Aynıoğlu, Aynur; Korkmaz, Fatime; Ersöz, Gülden; Tuna, Nazan; Ayaz, Celal; Karakeçili, Faruk; Keten, Derya; İnan, Dilara; Yazıcı, Saadet; Koçulu, Safiye; Yıldırmak, Taner

doi:10.1016/j.ijid.2016.07.003

Cited by 8 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Regardless of genotype and exposure to treatment, resistance mutations against DAAs were found in HCV isolates worldwide, as proofed by studies conducted on sequence databases (25,26). Furthermore, studies have shown the presence of DAAs resistance mutations in different unexposed populations (27,28). However, there are no clear indications for baseline screening of NS3 PIs resistance mutations in the absence of prior PIs exposure, nevertheless clinicians should be aware of Q80K polymorphism in 1a subtype isolates and resistant variants at positions 155, 156 and 168 in genotype 1 isolates (29).…”

Section: Discussionmentioning

confidence: 87%

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Dinu

Țârdei

Ceauşu

et al. 2018

Revista Romana De Medicina De Laborator

View full text Add to dashboard Cite

Background: Severe complications of chronic hepatitis C -i.e. cirrhosis and hepatocellular carcinoma -are important causes of morbidity and mortality worldwide. Despite the overwhelming rates of sustained virologic response achieved after therapy with different combinations of direct-acting antiviral drugs (DAAs), treatment failure is still recorded, and is due to the mutations harboured by hepatitis C virus (HCV) resistance associated variants (RAVs) selected during therapy. Baseline RAVs testing was found significant for guiding treatment in the cases of treatment failure and, sometimes, in naïve patients.Methods: Romanian chronic hepatitis C patients unexposed to DAAs and infected with subtype 1b HCV were studied. Serum samples were used for Sanger population sequencing of a fragment containing NS3 viral protease, known to harbour resistance mutation against protease inhibitors (PIs).Results: Catalytic triad and zinc-binding site in the studied sequences were conserved. Low-intermediate resistance mutations to first generation PIs were detected either alone or in conjunction with resistance substitutions associated with second generation PIs. Cross-resistance and reduced susceptibility to certain DAAs were observed.Discussion: This study focused on HCV patients infected with subtype 1b strains, the most prevalent in Romania. The rate of RAVs found in this work is consistent with the results reported by similar studies from other countries. Noticeably, numerous polymorphisms of unknown significance to DAAs resistance, but reflecting the

show abstract

Section: Discussionmentioning

confidence: 87%

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Dinu

Țârdei

Ceauşu

et al. 2018

Revista Romana De Medicina De Laborator

View full text Add to dashboard Cite

show abstract

“…The Y93H is a mutation related to cross-resistance in the NS5A inhibitor group (34). However, Y93H mutation was the first case to be reported in Turkey (35,36). These findings suggested the resistance analysis, as experienced in CHC patients on therapy should remain a basic part of the management.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Direct Acting Antivirals Efficiency in Turkish Patients with Chronic Hepatitis C Under Strict Rules

Sarıgül¹,

Sayan

User³

et al. 2019

Hepat Mon

Self Cite

View full text Add to dashboard Cite

In chronic hepatitis C treatment, direct acting antivirals have a strong effect and are well tolerated since 2014, yet it is unclear whether resource-constrained countries have the same achievement. This study aimed at evaluating direct acting antivirals used to treat Turkish chronic hepatitis C patients between the years of 2016 to 2017. Within the one-year period, 101 out of 105 patients reached a sustained virological response rate. The type of direct acting antivirals and treatment length were chosen according to the Health Implementation Guideline of Turkey. The analyses of effectiveness according to therapeutic regimes showed the following sustained virological response rate: Ledipasvir/sofosbuvir and +/-; ribavirin (97%), ombitasvir/paritepravir/dasabuvir and +/-; ribavirin (100%) and sofosbuvir + ribavirin (100%). One patient had virological relapse on the 12th week by the end of the therapy. In this patient, cross-resistance mutation Y93H was specified for the NS5A region. On the other hand, amino acid changes, S282G and C316S, were determined in the NS5B region. The adverse effects were 22% in all patients. Most of them were mild or moderate. The researchers concluded that the results of the highly efficient and well-tolerated therapy with direct acting antivirals could be examples in resource-constrained countries. In addition, resistant variants should be detected after unsuccessful treatment in the management of new therapy options.

show abstract

“…Ciddi fibrozu olan hastalar da siroz açısından klinik (splenomegali, karında asit, portal hipertansiyon, özofagus varisi, palmar eritem, periferik telanjiyektaziler) ve laboratuvar (serum bilirübin ve albümin değerleri, protrombin zamanı) olarak değerlendirilmelidir (57)(58)(59). İleri derecede fibrozu (METAVIR skoru F3/4 evresinde) olan sirotik hastalar HSK gelişmesi açısından 6 ayda bir izlenmelidir (51,60).…”

Section: Karaciğer Hastalığının şIddeti Ve Bazal Virolojik Parametrelerunclassified

“…Ayrıca doğal dirençlerin KVY üzerine önemli bir etkisi de gösterilmemiştir. Bu nedenle tedavi öncesinde rutin direnç analizi yapılması bugün için önerilmemektedir (51,60,61 …”

Section: Karaciğer Hastalığının şIddeti Ve Bazal Virolojik Parametrelerunclassified

“…Türk Klinik Mikrobiyoloji ve İnfeksiyon Hastalıkları Derneği Viral Hepatit Çalışma Grubu'nun (VHÇG) 2013 yılında ulusal düzeyde yaptığı bir çalışmada Türkiye'de doğal TVR, BOC, SMV ve faldaprevir (FDV) direnci mutasyonları sırasıyla %15, %14, %6 ve %7 olarak tanımlanmıştır (60). Ülkemizde yapı-lan güncel bir olgu sunumuna göre PegIFN ve RBV tedavisine yanıtsız ve TVR'li kombinasyon tedavisinin 12. haftasında viral "rebound" gelişen bir KHC'li hastada T54S, Q80L, A156T ve N174S mutasyonlarıyla PTV'ye duyarlılık, TVR, BOC ve SMV'ye çapraz direnç tanımlanmıştır (136).…”

Section: Doğrudan Etkili Antiviraller Ve Direnç Sorunuunclassified

See 1 more Smart Citation

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

Aygen¹,

Demirtürk²,

Türker³

et al. 2017

Klimik Dergisi

Self Cite

View full text Add to dashboard Cite

show abstract

Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

Abstract: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Cited by 8 publications

References 35 publications

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Evaluation of Direct Acting Antivirals Efficiency in Turkish Patients with Chronic Hepatitis C Under Strict Rules

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

Contact Info

Product

Resources

About