Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 8, 2017; 9(34): 1270-1277
Published online Dec 8, 2017. doi: 10.4254/wjh.v9.i34.1270
Liver decompensation predicts ribavirin overexposure in hepatitis C virus patients treated with direct-acting antivirals
Viola Guardigni, Lorenzo Badia, Matteo Conti, Matteo Rinaldi, Rita Mancini, Pierluigi Viale, Gabriella Verucchi
Viola Guardigni, Lorenzo Badia, Matteo Rinaldi, Pierluigi Viale, Gabriella Verucchi, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna 40138, Italy
Viola Guardigni, Lorenzo Badia, Gabriella Verucchi, Research Centre for the Study of Hepatitis, University of Bologna, Bologna 40138, Italy
Matteo Conti, Rita Mancini, Metropolitan Laboratory, Maggiore Hospital, Bologna 40133, Italy
Author contributions: Guardigni V carried out the statistical analysis and drafting the manuscript; Guardigni V and Badia L developed concept and design of the study; all authors were involved in data collection, interpretation of data and editing of the manuscript.
Institutional review board statement: Formal institutional approval was not deemed necessary since anonymised data routinely collected in our centre for clinical practice purposes were used.
Informed consent statement: All study participants provided informed consent prior to study inclusion.
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Viola Guardigni, MD, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, via G. Massarenti 9, Bologna 40138, Italy. viola.guardigni2@unibo.it
Telephone: +39-0512-144301 Fax: +39-0512-144301
Received: May 29, 2017
Peer-review started: June 1, 2017
First decision: July 4, 2017
Revised: August 2, 2017
Accepted: October 15, 2017
Article in press: October 16, 2017
Published online: December 8, 2017
Processing time: 189 Days and 17.4 Hours
Abstract
AIM

To determine whether ribavirin (RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens.

METHODS

We included patients with hepatitis C virus and cirrhosis [Child-Pugh (CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weight-based RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy.

RESULTS

We studied 68 patients: 54 with compensated (CP-B) and 14 with decompensated (CP-A) cirrhosis. Patients with decompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8 (P < 0.035). RBV levels were positively correlated with Hb loss over the treatment (P < 0.04). Majority (71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated (95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage.

CONCLUSION

Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease (CP-B) treated with direct-acting antivirals.

Keywords: Hepatitis C; Direct-acting antivirals; Ribavirin; Therapeutic drug monitoring; Decompensated cirrhosis

Core tip: In this study, patients with decompensated cirrhosis displayed higher plasma ribavirin concentrations in comparison to compensated patients, when treated with Interferon-free regimens for hepatitis C. Higher ribavirin levels were found to lead to greater rates of related toxicities and Child-Pugh class resulted independently associated with ribavirin plasma levels, in our population. Our findings suggest that ribavirin concentrations should be strictly monitored in subjects with advanced liver disease, during direct-acting antivirals-treatment. An early dosage adjustment of ribavirin should be performed when high levels of this antiviral are detected in patients’ plasma, in order to avoid toxicities among these frail individuals.