{"id":9939,"date":"2020-04-23T03:51:50","date_gmt":"2020-04-23T00:51:50","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/virusul-hepatitei-c-genotipare\/"},"modified":"2026-03-05T13:21:26","modified_gmt":"2026-03-05T11:21:26","slug":"virusul-hepatitei-c-genotipare","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/virusul-hepatitei-c-genotipare\/","title":{"rendered":"\u0412\u0438\u0440\u0443\u0441 \u0433\u0435\u043f\u0430\u0442\u0438\u0442\u0430 \u0421 \u2013 \u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435"},"content":{"rendered":"<p><strong><em>Informa\u0163ii generale \u015fi recomand\u0103ri<\/em><\/strong><\/p>\n<p>Virusul hepatitei C (VHC) constituie un agent patogen cu prevalen\u021b\u0103 global\u0103 \u0219i o cauz\u0103 principal\u0103 de morbiditate \u0219i mortalitate. Conform celor mai recente estim\u0103ri, seroprevalen\u021ba VHC a crescut \u00een ultimii 15 ani la 2.8%, echivalent\u0103 cu &gt; 185 milioane de infec\u021bii \u00een \u00eentreaga lume. Infec\u021bia VHC persistent\u0103 este asociat\u0103 cu dezvoltarea cirozei hepatice, a carcinomului hepatocelular \u0219i a insuficien\u021bei hepatice cu o rat\u0103 \u00eenalt\u0103 de deces.<\/p>\n<p>Asemenea altor virusuri ARN, VHC prezint\u0103 la nivel nucleotidic o diversitate genetic\u0103 considerabil\u0103 ceea ce constituie o provocare major\u0103 at\u00e2t pentru dezvoltarea\u00a0 vaccinurilor anti-VHC c\u00e2t \u0219i a terapiilor pangenotipice.<\/p>\n<p>Pe baza analizei filogenetice a secven\u0163ei genomice tulpinile VHC sunt clasificate \u00een momentul de fa\u021b\u0103 \u00een 7 genotipuri distincte (VHC 1-7) ce difer\u0103 unul de cel\u0103lalt la nivelul secven\u0163elor nucleotidice \u00een propor\u0163ie de 30-35% \u0219i \u00een peste 50 de subtipuri \u00eentre care se \u00eenregistreaz\u0103 o diferen\u0163\u0103 de 15-25%. \u00cen plus, la persoanele infectate, VHC circul\u0103 \u015fi se comport\u0103 ca un amestec de popula\u0163ii virale distincte denumite cvasispecii<sup>1;2<\/sup>.<\/p>\n<p>Genomul VHC este alc\u0103tuit din domenii care difer\u0103 mult \u00een ceea ce prive\u015fte rata muta\u0163iilor \u015fi variabilitatea secven\u0163elor nucleotidice. Astfel, regiunea netranslatat\u0103 de la cap\u0103tul 5\u2019 al genomului (5\u2019UTR) reprezint\u0103 domeniul cel mai bine conservat, cu rata evolutiv\u0103 cea mai lent\u0103. Urmeaz\u0103 apoi gena C (core) care codific\u0103 miezul nucleocapsidic proteic \u015fi care evolueaz\u0103 de trei ori mai rapid \u00een compara\u0163ie cu regiunea 5\u2019UTR. Genele care codific\u0103 proteinele de \u00eenveli\u015f E1 \u015fi E2 constituie regiunea hipervariabil\u0103, care difer\u0103 de la un izolat la altul. Aceasta permite virusului s\u0103 evite mecanismele imunologice ale gazdelor \u00eendreptate \u00eempotriva proteinelor accesibile din \u00eenveli\u015ful viral<sup>3<\/sup>.<\/p>\n<p>Distribu\u021bia geografic\u0103 global\u0103 actual\u0103 a genotipurilor VHC este complex\u0103. Este larg recunoscut faptul c\u0103 subtipurile 1a, 1b, 2a \u015fi 3a ce apar\u021bin \u201cgrupului epidemic\u201d au o distribu\u0163ie global\u0103 \u015fi sunt responsabile pentru majoritatea infec\u0163iilor din \u00eentreaga lume. R\u0103sp\u00e2ndirea global\u0103 rapid\u0103 a acestor subtipuri a rezultat din transmiterea lor eficient\u0103 prin produse de s\u00e2nge infectate \u015fi administrarea de droguri intravenoase. Subtipurile 1b \u015fi 2a sunt asociate predominant cu transmiterea prin produse de s\u00e2nge iar prevalen\u0163a lor relativ\u0103 a sc\u0103zut \u00een ultimii ani ca urmare a \u00eembun\u0103t\u0103\u0163irii screening-ului donatorilor. Subtipurile 1a \u015fi 3a se \u00eent\u00e2lnesc \u00een principal la dependen\u0163ii de droguri iar prevalen\u0163a acestora este \u00een cre\u015ftere. Alte subtipuri VHC sunt considerate \u201cendemice\u201d; acestea sunt mai rare \u0219i au circulat o perioad\u0103 de timp \u00eendelungat\u0103 \u00een arii geografice restr\u00e2nse. Astfel, subtipuri endemice ale genotipului 1 sunt descrise \u00een Africa de Vest iar ale genotipului 3 \u00een sudul Asiei. Genotipul 4 este predominant \u00een Africa Central\u0103 \u0219i Orientul Mijlociu iar genotipurile 5 \u0219i 6 sunt limitate la Africa de Sud \u0219i respectiv sud-estul Asiei<sup>1;2;3<\/sup>. P\u00e2n\u0103 \u00een prezent, a fost raportat\u0103 o singur\u0103 infec\u021bie cu genotipul VHC 7 \u00een Canada la o persoan\u0103 provenind din Africa Central\u0103<sup>1<\/sup>.<\/p>\n<p>Conform unor date recente de prevalen\u021b\u0103 global\u0103 VHC, genotipul 1 este cel mai prevalent (46.2% din toate cazurile de infec\u021bie VHC), fiind urmat de genotipul 3 (30.1%); genotipurile 2, 4 \u0219i 6 sunt responsabile de 22.8% din cazuri iar genotipul 5 de &lt; 1% din cazurile de infec\u021bie VHC. \u00cen timp ce genotipurile 1 \u0219i 3 predomin\u0103 \u00een majoritatea \u021b\u0103rilor indiferent de situa\u021bia lor economic\u0103, genotipurile 4 \u0219i 5 sunt prevalente \u00een \u021b\u0103rile cu nivel economic sc\u0103zut<sup>1<\/sup>.<\/p>\n<p>\u00cen \u0163ara noastr\u0103 predomin\u0103 genotipul 1b \u015fi un amestec de genotipuri 1a \u015fi 1b<sup>4<\/sup>. Un studiu efectuat la Institutul Matei Bal\u015f \u00een Bucure\u015fti pe 670 pacien\u0163i a indicat o prevalen\u0163\u0103 de 99.7% a \u00a0genotipului 1 VHC<sup>5<\/sup>.<\/p>\n<p>\u021ainta terapiei antivirale este vindecarea infec\u021biei VHC. R\u0103spunsul virusologic sus\u021binut (RVS) \u00a0este definit printr-un ARN VHC nedetectabil la 12 \u0219i 24 s\u0103pt\u0103m\u00e2ni de la \u00eencheierea tratamentului. Infec\u021bia VHC este vindecat\u0103 \u00een peste 99% din cazurile \u00een care s-a ob\u021binut RVS. La pacien\u021bii f\u0103r\u0103 ciroz\u0103 RVS este asociat \u00een general cu rezolu\u021bia bolii hepatice, \u00een timp ce la cei cu ciroz\u0103, de\u0219i fibroza hepatic\u0103 poate regresa \u0219i se reduce riscul de a dezvolta insuficien\u021b\u0103 hepatic\u0103 \u0219i hipertensiune portal\u0103, nu este eliminat complet riscul de carcinom hepato-celular.<\/p>\n<p>P\u00e2n\u0103 \u00een 2011 tratamentul s-a bazat pe combinarea interferonului \u03b1 pegylat cu ribavirina, rata de r\u0103spuns fiind diferit\u0103 \u00een func\u021bie de genotipul VHC. Cu aceast\u0103 abordare terapeutic\u0103 s-a ob\u021binut pentru genotipul 1 VHC o rat\u0103 de RVS de aproximativ 40% \u00een America de Nord \u0219i de 50% \u00een Europa de Vest. Rate mai mari de RVS (p\u00e2n\u0103 la 80%) au fost ob\u021binute pentru genotipurile 2, 3, \u00a05 \u0219i 6, \u00een timp ce pentru genotipul 4 s-au ob\u021binut rate de RVS intermediare<sup>6<\/sup>.<\/p>\n<p>Introducerea medicamentelor cu ac\u021biune antiviral\u0103 direct\u0103 a \u00eembun\u0103t\u0103\u021bit dramatic rata de succes a tratamentului \u00een compara\u021bie cu regimul terapeutic clasic. Prima genera\u021bie de antivirale directe a inclus inhibitorii de proteaze NS3\/4A \u2013 telaprevir \u0219i boceprevir \u2013 care administra\u021bi \u00eempreun\u0103 cu tratamentul clasic \u2013 interferonul \u03b1 pegylat cu ribavirina (\u201ctripla terapie\u201d) la pacien\u021bii cu genotipul 1 VHC a condus la rate de RVS de 60-75%. Cu toate acestea, datorit\u0103 riscului mare de reac\u021bii adverse \u0219i a costului ridicat acest protocol nu mai este recomandat \u00een prezent. \u00cen 2014, 3 noi medicamente au primit aprobare pentru a fi utilizate \u00een UE: <em>sofosbuvir<\/em> (analog nucleotidic pangenotipic, inhibitor al ARN polimerazei ARN-dependente VHC), <em>simeprevir<\/em> (inhibitor de proteaze NS3\/4A pentru genotipurile 1 \u0219i 4) \u0219i <em>daclatasvir<\/em> (inhibitor NS5A pangenotipic). Fiecare din aceste 3 antivirale poate fi folosit ca un component al triplelor terapii cu interferon \u03b1 pegylat cu ribavirin\u0103, ob\u021bin\u00e2ndu-se rate de RVS de 60-100% \u00een func\u021bie de preparatul utilizat, genotipul VHC, prezen\u021ba unor substitu\u021bii de aminoacizi preexistente care confer\u0103 rezisten\u021b\u0103 la antiviralul cu ac\u021biune direct\u0103\u00a0 folosit \u0219i severitatea afec\u021biunii hepatice. Odat\u0103 cu aprobarea acestor 3 noi medicamente au \u00eenceput s\u0103 fie utilizate \u00een Europa, pe parcursul anului 2014, combina\u021bii de antivirale f\u0103r\u0103 interferon, ini\u021bial la pacien\u021bii cu boal\u0103 hepatic\u0103 \u00een stadiu avansat (scor METAVIR F3, F4). Combina\u021bia de sofosbuvir \u0219i ribavirin\u0103 este indicat\u0103 la pacien\u021bii infecta\u021bi cu genotipurile VHC 2 (12 s\u0103pt\u0103m\u00e2ni) \u0219i 3 (24 s\u0103pt\u0103m\u00e2ni) cu rate de RVS de 80-95%. Administrarea combinat\u0103 de sofosbuvir \u0219i simeprevir, cu sau f\u0103r\u0103 ribavirin\u0103 s-a bazat pe studiul de faz\u0103 II\u00a0 COSMOS care a raportat o rat\u0103 de RVS de 93-100% pentru genotipul 1. De asemenea, administrarea combinat\u0103 de sofosbuvir \u0219i daclatasvir, cu sau f\u0103r\u0103 ribavirin\u0103, la pacien\u021bii cu boal\u0103 hepatic\u0103 \u00een stadiu avansat \u0219i genotip 1 s-a bazat pe rezultatele unui studiu de faz\u0103 II \u00een care s-au \u00eenregistrat de rate de RVS de 95-100%<sup>2;6;7<\/sup>.<\/p>\n<p>La \u00eenceputul anului 2015 Comisia European\u0103 a autorizat punerea pe pia\u021b\u0103 a unui nou medicament \u2013 <em><strong>Viekirax+Exviera<\/strong><\/em><strong>, <\/strong>iar tratamentul a fost aprobat pentru administrare cu sau f\u0103r\u0103 ribavirin\u0103 pentru pacien\u021bii cu infec\u021bie cronic\u0103 VHC genotipul 1, inclusiv pentru cei cu ciroz\u0103 hepatic\u0103 compensat\u0103, pacien\u021bi coinfecta\u021bi cu HIV-1, pacien\u021bi afla\u021bi \u00een tratament substitutiv al dependen\u021bei de opiacee \u0219i pacien\u021bi care primesc transplant hepatic. \u00cen plus, medicamentul a fost aprobat \u00een combina\u021bie cu ribavirina pentru pacien\u021bii cu hepatit\u0103 C cronic\u0103 genotip 4.\u00a0\u00a0 Viekirax const\u0103 din combina\u021bia \u00een doz\u0103 fix\u0103 de paritaprevir 150 mg (inhibitorul de proteaz\u0103 NS3\/4A) \u015fi ritonavir 100 mg (inhibitor de CYP3A4 ce cre\u0219te concentra\u021bia plasmatic\u0103 de paritaprevir) \u00een asociere cu ombitasvir 25 mg (inhibitor NS5A), administrat\u0103 o dat\u0103 pe zi, iar Exviera const\u0103 din dasabuvir 250 mg (inhibitor non-nucleozidic al ARN polimerazei ARN dependente) administrat de dou\u0103 ori pe zi, cu sau f\u0103r\u0103 ribavirin\u0103. Aceast\u0103 combina\u021bie de antivirale f\u0103r\u0103 interferon \u021binte\u0219te sinergic replicarea VHC la 3 nivele distincte. Conform rezultatelor din 6 trialuri de faz\u0103 III \u0219i 2 studii de faz\u0103 II RVS global la 12 s\u0103pt\u0103m\u00e2ni pentru pacien\u021bii infecta\u021bi cu genotipul 1 a fost de peste 96%<sup>6;7<\/sup>.<\/p>\n<p>\u00cen concluzie, se recomand\u0103 ca genotiparea HCV s\u0103 fie efectuat\u0103 \u00een toate infec\u0163iile cu virus C \u00eenaintea \u00eenceperii oric\u0103rui tratament, \u00een vederea select\u0103rii protocolului adecvat<sup>6<\/sup>.<\/p>\n<p>Testul efectuat \u00een laboratorul nostru folose\u015fte tehnica RT-PCR (transcrierea invers\u0103 a ARN-ului \u021bint\u0103 cu generarea de ADN complementar ce va fi amplificat prin reac\u021bia PCR, cu detec\u021bia \u00een timp real a ampliconului) \u0219i sonde oligonucleotidice marcate fluorescent specifice fiec\u0103rui genotip pentru identificarea genotipurilor HCV de la 1 la 6 \u015fi a subtipurilor a \u015fi b ale genotipului 1<sup>8<\/sup>.<\/p>\n<p><em><strong>Specimen recoltat<\/strong><\/em> \u2013 s\u00e2nge venos<sup>8<\/sup>.<\/p>\n<p><em><strong>Recipient de recoltare<\/strong><\/em>\u00a0-\u00a0<span data-olk-copy-source=\"MessageBody\">Plasma EDTA congelat, trebuie recoltate\u00a0 2 eprubete EDTE (ambele se legati cu elastic)<\/span>.<\/p>\n<p><em><strong>Prelucrare necesara dup\u0103 recoltare <\/strong><\/em>\u2013 se separ\u0103\u00a0 plasma prin centrifugare<sup>8<\/sup>.<\/p>\n<p><em><strong>Volum\u00a0de prob\u0103\u00a0<\/strong><\/em>\u2013 minim\u00a01 mL plasm\u0103<sup>8<\/sup>.<\/p>\n<p><em><strong>Stabilitate prob\u0103<\/strong><\/em> \u2013\u00a0probele de plasm\u0103 sunt\u00a0stabile\u00a0<em>1 lun\u0103\u00a0<\/em>\u00a0la -20\u00b0C<sup>8<\/sup>.<\/p>\n<p><strong><em>Metod\u0103 <\/em><\/strong>- <u>Real-time PCR pe platforma automat\u0103 m2000 (Abbott)<\/u>; testul utilizeaz\u0103 ca \u021binte ale amplific\u0103rii o secven\u021b\u0103 din regiunea 5\u2019UTR a genomului viral pentru detectarea genotipurilor 1-6 \u0219i regiunea NS5B pentru identificarea separat\u0103 a subtipurilor 1a \u0219i 1b; sunt folosite 4 seturi de primeri fiind necesare 3 tipuri de reac\u021bii separate:<\/p>\n<ul>\n<li>reac\u021bia A: detecteaz\u0103 toate izolatele VHC, izolatele cu subtipul 1a \u0219i izolatele cu genotipul 3;<\/li>\n<li>reac\u021bia B: detecteaz\u0103 izolatele cu genotipul 2, subtipul 1b \u0219i genotipul 1;<\/li>\n<li>reac\u021bia C: detecteaz\u0103 izolatele cu genotipurile 4, 5 \u0219i 6.<\/li>\n<\/ul>\n<p>\u00cen\u00a0 momentul prepar\u0103rii fiec\u0103rei probei de pacient se introduce o secven\u021b\u0103 ARN f\u0103r\u0103 leg\u0103tur\u0103 cu genomul VHC ce va servi drept control intern pentru toate etapele procesului. Sunt utilizate de asemenea \u0219i probe de control (pozitiv \u0219i negativ) la fiecare rulare a probelor.<\/p>\n<p>Acurate\u021bea testului a fost demonstrat\u0103 prin analiza a 162 de izolate VHC av\u00e2nd genotipul 1 (110 cu genotipul 1a \u0219i 58 cu genotipul 1b), 41 izolate VHC genotipul 2, 27 izolate VHC genotipul 3, 28 izolate VHC genotipul 4, 14 izolate VHC genotipul 5 \u0219i 12 izolate VHC genotipul 6. Pentru stabilirea genotipului de referin\u021b\u0103 din fiecare prob\u0103 analizat\u0103 a fost utilizat\u0103 tehnica de secven\u021biere a acizilor nucleici. Concordan\u021ba dintre cele 2 metode (genotipare prin PCR \u0219i secven\u021biere) a fost de 97.59% pentru toate genotipurile identificate, de 97.27% pentru subtipul 1a \u0219i de 91.38% pentru subtipul 1b<sup>8<\/sup>.<\/p>\n<p><strong><em>Limite \u015fi interferen\u0163e<\/em><\/strong><\/p>\n<p>Efectuarea genotip\u0103rii HCV nu este recomandat\u0103 pentru screening-ul sau confirmarea infec\u0163iei HCV. Testul este posibil numai \u00een cazul existen\u0163ei unei viremii C &gt; 500 UI\/mL.<\/p>\n<p>Sonda oligonucleotidic\u0103 corespunz\u0103toare regiunii 5\u2019UTR a genomului VHC de genotip 1 nu reac\u021bioneaz\u0103 \u00eencruci\u0219at cu probele ce con\u021bin VHC subtipul 6a dar poate prezenta reactivitate \u00eencruci\u0219at\u0103 cu subtipul 6b \u0219i cu unele subtipuri non6a\/6b ale genotipului 6.<\/p>\n<p>\u00cen anumite cazuri se pot ob\u0163ine rezultate neinterpretabile datorit\u0103 heterogenit\u0103\u0163ii secven\u0163elor genomului HCV, infec\u0163iior mixte sau existen\u0163ei (rare) de tulpini VHC recombinate<sup>8<\/sup>.<\/p>\n<p align=\"center\"><span style=\"font-family: 'Arial Narrow',sans-serif; font-size: 10pt;\"><span style=\"color: #000000;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/span><\/p>\n<ol>\n<li>Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. Global distribution and prevalence of hepatitis C virus genotypes. <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25069599\" rel=\"nofollow noopener\" target=\"_blank\">Hepatology.<\/a> 2015 Jan;61(1):77-87.<\/li>\n<li>Cuypers L, Li G, Libin P, Piampongsant S, Vandamme AM, Theys K. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance. Viruses. 2015 Sep 6;7(9):5018-39.<\/li>\n<li>Stumpf MP, Phybus OG. Genetic diversity and models of viral evolution for the hepatitis C virus.\u00a0FEMS Microbiol Lett. 2002 Sep 10;214(2):143-52.<\/li>\n<li>Ileana Constantinescu, Institutul Clinic Fundeni. Genotiparea virusurilor hepatitice \u00een Rom\u00e2nia. Simpozion iunie 2008, Tg. Mure\u015f: Rolul tehnicilor de biologie molecular\u0103 \u00een elucidarea mecanismelor infec\u0163iei cu virusul\u00a0\u00a0hepatitic de tip C, precum \u015fi \u00een descoperirea de noi markeri pentru fibroz\u0103 \u015fi carcinomul hepatocelular asociate cu aceast\u0103 infec\u0163ie.<\/li>\n<li>Neaga Emil. Prevalen\u0163a genotipului 1 HCV \u00een Rom\u00e2nia. Simpozion iunie 2008, Tg. Mure\u015f: Rolul tehnicilor de biologie molecular\u0103 \u00een elucidarea mecanismelor infec\u0163iei cu virusul hepatitic de tip C, precum \u015fi \u00een descoperirea de noi markeri pentru fibroz\u0103 \u015fi carcinomul hepatocelular asociate cu acast\u0103 infec\u0163ie.<\/li>\n<li>European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015 Jul;63(1):199-236.<\/li>\n<li>Lam BP, Jeffers T, Younoszai Z, Fazel Y, Younossi ZM. The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment. Therap Adv Gastroenterol. 2015;8(5):298-312.<\/li>\n<li>Laborator Synevo. Referin\u021bele specifice tehnologiei de lucru utilizate 2015. Ref Type: Catalog.<\/li>\n<\/ol>\n<p style=\"text-align: center;\"><span style=\"font-size: small;\">\u00a0<\/span><\/p>","protected":false},"excerpt":{"rendered":"<p>\u0412\u0438\u0440\u0443\u0441 \u0433\u0435\u043f\u0430\u0442\u0438\u0442\u0430 \u0421 (\u0412\u0413\u0421) \u0441\u043f\u043e\u0441\u043e\u0431\u0435\u043d \u043f\u043e\u0440\u0430\u0436\u0430\u0442\u044c \u043a\u043b\u0435\u0442\u043a\u0438 \u043f\u0435\u0447\u0435\u043d\u0438, \u0430 \u0442\u0430\u043a\u0436\u0435 \u043d\u0435\u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u043a\u043b\u0435\u0442\u043a\u0438 \u043a\u0440\u043e\u0432\u0438 (\u043d\u0435\u0439\u0442\u0440\u043e\u0444\u0438\u043b\u044b, \u043c\u043e\u043d\u043e\u0446\u0438\u0442\u044b, \u0412-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b). \u0412 \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u043c \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u044f \u043f\u0435\u0440\u0435\u0434\u0430\u0435\u0442\u0441\u044f \u0447\u0435\u0440\u0435\u0437 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decoding=\"async\" class=\"alignnone wp-image-62297 size-full\" src=\"https:\/\/www.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441.png\" alt=\"\" width=\"801\" height=\"312\" srcset=\"https:\/\/old.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441.png 801w, https:\/\/old.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441-300x117.png 300w, https:\/\/old.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441-768x299.png 768w, https:\/\/old.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441-18x7.png 18w, https:\/\/old.synevo.md\/wp-content\/uploads\/2020\/04\/\u0433\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435_\u0433\u0435\u043f\u0430\u0442\u0438\u0442_\u0441-600x234.png 600w\" sizes=\"(max-width: 801px) 100vw, 801px\" 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