Evidenze II - HCV

Aggiornato il 20/03/2026

di Daniele

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Appunti di Evidenze medico chirurgiche II del professor Coppola sulla terapia dell'epatite cronica da HCV con analisi dei seguenti argomenti: statistiche dell'infezione, genotipi HCV, …

Esame Evidenze II

Facoltà Medicina e chirurgia

Dal corso del Prof. Coppola Nicola

Università Università degli studi della Campania "Luigi Vanvitelli"

A.A. 2012-2013

76 pagine

Appunto

Scarica

Estratto del documento

Corso integrato di evidenze medico-chirurgiche

Terapia dell'epatite cronica da HCV

48 weeks (AI)

Genotype 1: Low viral load and negative at week 4 24 weeks (BII) - without early virological response - 72 weeks (BII)
Genotype 2: 24 weeks (AI)
Genotype 3: 24 weeks (AI)
Genotype 3 and low viral load: 12 weeks (BI)
Genotype 3 and high viral load: 24 weeks (BI) or 48 weeks (BIII)

Terapia anti-HCV

Peg IFN alpha 2a vs 2b Futuro NEJM 09 NEJM 0940% SVR SVR200 Peg a2b low Peg a2b high Peg a2a

N° of pts: 1016 1019 1035 NEJM 09

Treatment-naïve patients with chronic hepatitis C were randomly (1:1) assigned after stratification for HCV genotype to either regimen for 24 or 48 weeks according to virus genotype. RBV was weight dosed in all genotype patients receiving 1.5 mcg/Kg/week PegIFNα2b (800-1200 mg/day) and in HCV-1 and HCV-4 patients treated with 180 mcg/week PegIFNa2a (1000-1200 mg/day). Patients with HCV-2 and HCV-3 on PegIFNα2a received a fixed dose of 800 mg/day RBV. Gastroenterology 2010

Patients with Ribavirin >13.1 mg/kg/die806040% pts 200 Peg a2b low Peg a2b high Peg a2a

N° of pts: 1016 1019 1035 NEJM 09 Gastroenterology 2010 SVR Hepatology 2010 Hepatology 2009

IL28B Genotype: A strong predictor of SVR with PegIFN/RBV

Whites (n = 871) Blacks (n = 191) Hispanics (n = 75)

Factor Associated With SVR Odds Ratio (95% CI) 7.3 IL28B rs12979860 4.2 genotype (CC vs TT) 3.0 6.1 Baseline HCV RNA 5.1 (< vs 600,000 IU/mL) ≥ 1.1 5.6 Baseline fibrosis 2.4 (METAVIR F0-F2 vs F3-F4) 4.10.1 1.0 10.0 Ge D, et al. Nature. 2009;461:399-401.

Nuovi farmaci

Receptor binding Transport and endocytosis and release Fusion and uncoating ER lumen Virion(+) RNA LD assemblyLD Translation and LDNS3/4 Membranous protease polyprotein NS5B polymerase RNA replication web inhibitors inhibitors processing ER lumen NS5A* inhibitors *Role in HCV lifecycle not well defined Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.

HCV inhibitors

Drug	Phase
NS3/4A protease inhibitors	Telaprevir III, Boceprevir III, MK-7009 II, Narlaprevir (SCH 900518) II, BI 201335 II, TMC435 II, R7227 (ITMN-191) II
NS5B polymerase (RdRp) inhibitors	Nucleos(t)ide analogue R7128 (RO5024048) II, IDX184 II, Nonnucleos(t)ide Filibuvir (PF-00868554) II, ANA598 II, GS 9190 II, ABT-333 II
NS5A inhibitors	BMS-790052 II

Randomized, placebo-controlled, phase II trial in USA

Week 12 Week 24 Week 48 µg/wk Placebo + PegIFN alfa-2a 180 + RBV 1000/1200 mg QD EOT (n = 75) TVR 750 mg every 8 hrs + EOT Treatment-naive PegIFN alfa-2a + RBV PegIFN alfa-2a + RBV patients infected (n = 79) with HCV TVR + †24-week PegIFN alfa-2a + genotype 1* SVR PegIFN alfa-2a + RBV RBV follow-up (n = 79) (N = 250) TVR + †24-week SVR PegIFN alfa-2a + RBV follow-up (n = 17) *Patients received TVR 1250-mg loading dose or placebo based on the arm to which they were †randomized. Patients must achieve undetectable HCV RNA at Week 4 (< 10 IU/mL) and at last test before stopping therapy at 12 or 24 weeks. NEJM 2009

Randomized, placebo-controlled, phase II trial in Europe

Week 12 Week 24 Week 48 µg/wk Placebo + PegIFN alfa-2a 180 + RBV 1000/1200 mg QD EOT (n = 82) †24-week TVR + SVR PegIFN alfa-2a + Treatment-naive PegIFN alfa-2a + RBV follow-up RBV patients infected (n = 81) with HCV TVR 750 mg every 8 hrs + †24-week genotype 1* PegIFN alfa-2a + RBV SVR (n = 82) follow-up (N = 334) TVR + †24-week SVR PegIFN alfa-2a follow-up (n = 78) *Patients received TVR 1250-mg loading dose or placebo based on the arm to which they were †randomized. Patients must achieve undetectable HCV RNA at Week 4 (< 10 IU/mL) and at last test NEJM 2009 before stopping therapy at 12 or 24 weeks.

Telaprevir nei pazienti naive, genotipo 1

[2]PROVE 2[1]PROVE 1100 P = .004 P = .002 P = .12 P = .02080 6967 P = .20% 61 60 Rate, 60 4641 36 SVR 3540200 T12/PR12 T12/PR24 PR48PR48 T12/PR48 T12/P12 T12/PR12 T12/PR24 (n = 17) (n = 82)(n = 75) (n = 79) (n = 79) (n = 78) (n = 82) (n = 81)1. McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838. 2. Hézode C, et al. N Engl J Med. 2009;360:1839-1850.

Oggi

Genotipo Durata del trattamento Dose di Ribavirina

1 Peg-IFN+Riba 48 settimane 1000-1200 mg
2 Peg-IFN+Riba 24 settimane 800 mg
3 Peg-IFN+Riba 24 settimane 800 mg
4 Peg-IFN+Riba 36 settimane 800-1000 mg

Futuro

Genotipo Durata del trattamento Dose di Ribavirina

1 Telapravir 12+ Peg+Riba 48 1000-1200 mg (24 week)
2 Peg-IFN+Riba 24 settimane* 800 mg
3 Peg-IFN+Riba 24 settimane 800 mg
4 Peg-IFN+Riba 36 settimane 800-1000 mg

Potential targets and approaches

Potential targets and approaches in the next 5 years

Immuno-specific Ribavirin modulators
New IFNs antivirals analogues
Therapeutic vaccines

Anteprima

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