Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis

Gambato M, Canini L, Lens S, Graw F, Perpinan E, Londono MC, Uprichard SL, Marino Z, Reverter E, Bartres C, Gonzalez P, Pla A, Costa J, Burra P, Cotler SJ, Forns X, Dahari H (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Liver International Wiley-Blackwell

Book Volume: 39

Pages Range: 826-834

Journal Issue: 5

DOI: 10.1111/liv.14014

Abstract

Background & Aims: Detailed hepatitis C virus (HCV) kinetics modelling is scarce in patients with advanced liver disease receiving direct-acting antivirals (DAAs). Due to budget restrictions, patients and health systems would benefit from the shortest possible treatment course. We investigated whether modelling very early HCV kinetics in cirrhotic patients under DAAs therapy could be used to individualize care and reduce treatment duration to achieve cure. Methods: We included 74 patients with HCV-related cirrhosis who received interferon-free treatments for 12-24 weeks. HCV genotype, liver disease stage and treatment regimen were recorded. Viral load was determined prospectively at very frequent intervals until target not detected (TND, <15 IU/mL). A viral kinetic model was used to predict time to cure based on HCV clearance in extracellular body fluid (CL-EF). Results: Sixty-eight patients (92%) achieved cure. Thirteen (18%) had MELD ≥15, 35 (47%) were Child-Pugh (CTP) ≥7. Median time to reach TND was 2 weeks (IQR: 1-4 weeks). Modelling indicated an average DAAs efficacy in blocking viral production of ε = 99.1%. HCV half-life (t 1/2 ) was significantly shorter in patients with CTP <7, LSM <21 kPa or MELD <15 (1.5 vs 2.5 hours; P = 0.0057). The overall median CL-EF was 5.6 weeks (4.1-7.8). A CTP >7 and a LSM ≥21 kPa were significantly (P = 0.016) associated with longer CL-EF. Conclusions: The study provides insights into HCV dynamics during DAAs therapy in patients with compensated and decompensated cirrhosis. Viral kinetics modelling suggests that treatment duration may be optimized in patients with compensated cirrhosis.

Authors with CRIS profile

Frederik Graw

Involved external institutions

Universitat de Barcelona (UB) / University of Barcelona ES Spain (ES) Loyola University Medical Center US United States (USA) (US) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Azienda Ospedaliera di Padova IT Italy (IT)

How to cite

APA:

Gambato, M., Canini, L., Lens, S., Graw, F., Perpinan, E., Londono, M.-C.,... Dahari, H. (2019). Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis. Liver International, 39(5), 826-834. https://doi.org/10.1111/liv.14014

MLA:

Gambato, Martina, et al. "Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis." Liver International 39.5 (2019): 826-834.

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