Nel 1989 comparvero due articoli su Science che recitavano che era stato isolato per la prima volta un virus ad RNA appartenente alla famiglia dei flavivirus e responsabile di quella strana epatite virale clinicamente non classificabile (Epatite NANB, non A non B) che stava allarmando l’occidente quando l’epoca dei controlli trasfusionali non era ancora iniziata. Questo virus oggi lo conosciamo tutti con il nome di virus dell’epatite C.

Da moltissimi anni, a causa della particolari proprietà del virus, si è cercato invano di trovare una strategia terapeutica che non fosse solo in grado di controllare i sintomi ma di eradicare completamente la malattia ma senza successo. Difatti HCV è un virus epatotropico con caratteristica di dare in oltre l’80% dei casi infezioni croniche. Queste ultime nel 20-30% dei casi a lungo andare si possono trasformare in cirrosi epatica e di queste un 2-3% si possono trasformare in carcinoma epatocellulare. Questo accade fondamentalmente poiché HCV è un virus capace di evadere il sistema immunitario grazie alla regione ipervariabile all’ E2 cambiando continuamente mediante processi di drift antigenici gli epitopi del suo envelope proteico di rivestimento esprimendosi quindi in una condizione di ‘quasi specie’ all’interno dell’organismo ospite. Esistono 4  genotipi di HCV ognuno dei quali caratteristicamente dotati di un certo grado di aggressività. La presenza di un genotipo piuttosto che di un altro nelle infezioni incide sul successo delle terapie e quindi in definitiva sulla prognosi. Inoltre esiste anche un particolare polimorfismo cioè quello per l’IL-28 che incide sulla risposta terapeutica all’interferone.

Difatti fino a non molto tempo fa lo schema terapeutico per l’epatite C si basava fondamentalmente sulla terapia combinata a base di Ribavirina ed INF-alpha. La ribavirina è un analogo nucleosidico mentre l’interferone alpha è un immunostimolatore che induce l’espressione di MHC1 sulle cellule infette favorendone il riconoscimento a linfociti T CD8+ e quindi la citotossicità nonché aumenta l’espressione di citochine antivirali, l’attività di cellule NK e macrofagi

Negli ultimi anni si è poi passati a considerare una terapia per HCV simile a quella già esistente per l’HIV e cioè si è pensato di sviluppare inibitori di proteasi del virus allo scopo di smantellare tutto il macchinario enzimatico consentente al virus di stabilire un’infezione nella cellula ospite sfruttandone le strutture per la replicazione.

A tale scopo negli anni passati sono stati investiti delle industrie farmaceutiche miliardi di dollari per sviluppare smart drugs capaci di inibire selettivamente le proteasi del virus ma aventi bassa affinità per quelle dell’ospite. Così facendo è nata la classe degli inibitori delle proteasi NS3-4 di prima generazione come il Boceprevir o Telaprevir nei pazienti con HCV genotipo 1 e resistenti al trattamento classico che non avevano ancora iniziato alcun trattamento con altri antivirali. Successivamente fu sviluppato il Simeprevir attivo contro i genotipi 1,2 e 4 ma NON il 3 di HCV.
In tutti questi casi i pazienti svilupparono grandi resistenze e le terapie fallirono.

Negli ultimissimi anni però sono stati sviluppati inibitori di 3° generazione come il Grazoprevir con attività verso TUTTI i genotipi di HCV cui sono stati associati dei nuovi inibitori di proteasi e diretti anche contro la polimerasi del virus codificata da NS5B come il sofosbuvir o l’elbasivir con risultati eccellenti nelle terapie combinate sia nei soggetti naive al trattamento che già precedentemente trattati.

I dati dicono che i tassi di risposta virologica sostenuta a 12 settimane nel trattamento grazoprevir/elbasivir sono stati del 97% per i pazienti naïve al trattamento, non-cirrotici e co-infetti HIV, del 97% dei pazienti naïve al trattamento con cirrosi e dal 91% dei pazienti con precedente risposta nulla, con o senza cirrosi

Ciò significa che più di nove pazienti su 10 con questo trattamento guarisce dal virus in modo DEFINITIVO. Attualmente questi farmaci sono ancora in sperimentazione clinica (il Sofosbuvir già è stato commercializzato) ma dati i risultati si sta accelerando per la fine dello studio e la messa in commercio prevista per l’anno 2015 (in USA). Anche l’Agenzia europea del farmaco dovrebbe muoversi in breve tempo in tale direzione. Unico problema di questi farmaci sono i costi elevati ma, a dispetto dei benefici, crediamo che investire su di loro sia una grande anzi grandissima vittoria per tutto il mondo della scienza medica poiché significa aver battuto una volta e per sempre un virus problematico come quello dell’epatite C

Redazione | Nato a Torre del greco il 27/03/1992 5°anno facoltà di medicina e chirurgia Federico II Napoli Appassionato di molte discipline diverse la medicina rappresenta sicuramente la più importante. Non disdegno alcun settore ma le branche che più mi interessano sono quelle della diagnostica clinica, della dermatologia, della ricerca oncologica, della farmacologia, della pediatria e della medicina interna. La mia idea di medico è quella di un lavoro di gruppo che possa essere parte di un team multidisciplinare ben strutturato che garantisca ai pazienti un iter di cura completo ed efficace. Spero un giorno di poter fare esperienze anche in zone di guerra specialmente in medio oriente magari con MSF o Emergency

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