November 17, 2013

A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: The TT4 randomized trial

Digestive and Liver Disease

Available online 13 November 2013

In Press, Corrected ProofNote to users

Liver, Pancreas and Biliary Tract

Simona FranciosoaCristiana Almerighia, Paolo Forteb, Franco BandieracLorenzo NosottidRaffaella Lionettie, Gloria Talianif, Maria Rosaria Pirasg, Maria Laura Pontig, Giustino Parrutih, Francesco Di Candiloi, Silvia Gentilea, Paola Piccoloa, Angela Salsoa, Francesca Riccobellia, Sara Renzib, Maria Antonella Longoe, Marzia Montalbanoe, Salvatore Zaruc, Elisa Biliottif, Francesco Di Masih, Francesco Santopaoloa, Mario Angelicoa

a Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
b G. Careggi Hospital, University of Florence, Italy
c SS Annunziata Hospital, Sassari, Italy
d National Institute for Health Migration and Poverty (NIHMP), Rome, Italy
e National Institute of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy
f Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy
g G. Brotzu Hospital, Cagliari, Italy
h Ospedale Civile, Pescara, Italy
i S.M. Misericordia Hospital, Perugia, Italy


Background Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4).

Method 267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n = 180) or current standard-of-care (SoC, n = 87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2 log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment.

Results Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25 ± 15 vs. 36 ± 12.1 weeks], and for subgroups: G1 [35.3 ± 16.7 vs. 47.3 ± 2.6 weeks], G2 [18.3 ± 7.5 vs. 24 ± 2.8 weeks], G3 [15.2 ± 8.7 vs. 22.8 ± 3 weeks] and G4 [26.9 ± 13 vs. 48 weeks].

Conclusions In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.

Keywords HCV treatment; Dual therapy; Pegylated interferon; Ribavirin; Rapid viral response; Response-guided therapy; Individualized therapy


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