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Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients

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Abstract

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344–13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

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Acknowledgements

Other members of the GEHEP-SEIMC/HEPAVIR Group are: Helena Albendín, María Remedios Alemán, María del Mar Alonso, Victor Asensi, María José Blanco, Javier Borrallo, Rebeca Cabo, Ángela Camacho, Mario Frías Casas, Ángeles Castro, Antonio Collado, Sandra Cuellar, Francisca Cuenca, Marcial Delgado, Carlos Dueñas, Elisa Fernández, Carlos Galera, María Carmen Gálvez, Dácil García, Paloma Geijo Martínez, Ana Gómez, Juan Luis Gómez, Félix Gutiérrez, José Hernández, Jehovana Hernández, Jara Llenas-García, María Mancebo, José María Martín, Lorena Martínez, Rosa Martínez-Álvarez, Onofre Martínez Madrid, María del Mar Masiá, Nicolás Merchante, Patricia Monje, Marta Montero-Alonso, Rocío Nuñez, Guillermo Ojeda, Sergio Padilla, Catarina Robledano, Ricardo Pelazas, Elisabet Pérez, Inés Pérez-Camacho, Montserrat Pérez-Pérez, Berta Pernas, José Joaquín Portu, Miguel Raffo, Luis M. Real, Gabriel Reina, Sergio Reus, María José Ríos, Antonio Rivero, Joaquín Portilla, Purificación Rubio, Pablo Saíz de la Hoya, Ignacio de los Santos-Gil, Jesús Santos, Miriam Serrano, Marta Suárez-Santamaría, Francisco Téllez, Carla Toyas, Francisco Jesús Vera-Méndez, Antonio Vergara, David Vinuesa García.

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Authors and Affiliations

  1. Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain

    K. Neukam, J. Macías & J. A. Pineda

  2. Unit of Infectious Pathology, Hospital Universitario Alvaro Cunqueiro, Vigo, Spain

    L. E. Morano-Amado

  3. Unit of Infectious Diseases, Hospital Universitario Reina Sofía, Maimónides Institute of Biomedical Investigation of Cordoba (IMIBIC), University of Cordoba, Cordoba, Spain

    A. Rivero-Juárez

  4. Unit of Infectious Diseases, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain

    R. Granados

  5. Unit of Infectious Diseases, Hospital Universitario Puerto Real, Puerto Real, Spain

    A. Romero-Palacios

  6. Unit of Infectious Diseases, Hospital Universitario Virgen de la Victoria, Malaga, Spain

    M. Márquez

  7. Unit of Infectious Diseases, Complejo Hospitalario Universitario de Huelva, Huelva, Spain

    D. Merino

  8. Unit of Infectious Diseases, Consorcio Hospital General Universitario de Valencia, Valencia, Spain

    E. Ortega

  9. Unit of Infectious Diseases and Microbiology, AGS Norte de Cádiz, Jerez de la Frontera, Spain

    J. C. Alados-Arboledas

  10. Service of Internal Medicine, Hospital de Figueres-Fundació Salut Empordà, Figueres, Spain

    J. Cucurull

  11. Unit of Infectious Diseases, Complejo Hospitalario de Jaén, Jaen, Spain

    M. Omar

  12. Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain

    P. Ryan-Murua

Authors
  1. K. Neukam
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  2. L. E. Morano-Amado
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  3. A. Rivero-Juárez
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  4. J. Macías
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  5. R. Granados
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  6. A. Romero-Palacios
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  8. D. Merino
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  9. E. Ortega
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  14. J. A. Pineda
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Consortia

On behalf of the Grupo de Estudio de Hepatitis Vírica, of the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica: GEHEP-SEIMC and Grupo de Estudio de Hepatitis Vírica, of the Sociedad Andaluza de Enfermedades Infecciosas y Microbiología Clínica: HEPAVIR/Red de Investigación en SIDA (RIS-HEP07)

Corresponding author

Correspondence to K. Neukam.

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Funding

This work has been partially funded by the RD12/0017/0012 project as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluación, the Fondo Europeo de Desarrollo Regional (FEDER) and the Consejería de Salud of the Junta de Andalucía (grant numbers AC-0095-2013 and PI-0492-2012). K.N. is the recipient of a Miguel Servet research grant from the Instituto de Salud Carlos III (grant number CP13/00187). A.R.-J. is the recipient of a post-doctoral perfection grant from the Consejería de Salud of the Junta de Andalucía (grant number RH-0024/2013). J.M. is the recipient of a grant from the Servicio Andaluz de Salud of the Junta de Andalucía (grant number B-0037). J.A.P. is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS).

Conflict of interest

K.N. has received lecture fees from Janssen-Cilag, Roche, Bristol-Meyers Squibb and Merck Sharp & Dohme, research support from Janssen-Cilag, Bristol-Meyers Squibb, Merck Sharp & Dohme, Gilead Sciences and Abbott Pharmaceuticals and travel expenses from Janssen-Cilag, ViiV Healthcare, Roche, Bristol-Meyers Squibb and Merck Sharp & Dohme. A.R.-J. has received lecture fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, ViiV Healthcare and Roche. J.M. has been an investigator in clinical trials supported by Roche, Bristol-Myers Squibb and Abbott Pharmaceuticals and has received lecture fees from Roche, Gilead Sciences, Boehringer Ingelheim and Bristol-Myers Squibb and consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme and Schering-Plough. R.G. reports having received lecture fees from Roche, Gilead Sciences, Janssen Cilag and Merck Sharp & Dohme. He has received consultancy fees from Janssen Cilag and Abbvie. M.M. reports having received consulting fees from Gilead Sciences and Janssen-Cilag and lecture fees from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck-Sharp & Dome and ViiV Healthcare. D.M. reports having received consultancy fees from Janssen Cilag, Merck Sharp & Dohme, Bristol-Myers Squibb, Gilead Sciences, Abbvie and ViiV Healthcare. J.C. has received consultancy fees from Janssen Cilag, Bristol-Myers Squibb and Gilead Sciences and lecture fees from Janssen Cilag, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare and Merck Sharp & Dohme. M.O. has received lecture fees from Abbvie, ViiV Healthcare, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb and Merck Sharp & Dohme. J.A.P. reports having received consulting fees from GlaxoSmithKline, Bristol-Myers Squibb, Abbott Pharmaceuticals, Gilead Sciences, Merck Sharp & Dohme, Schering-Plough, Janssen-Cilag and Boehringer Ingelheim. He has received research support from GlaxoSmithKline, Roche, Bristol-Myers Squibb, Schering-Plough, Abbott Pharmaceuticals and Boehringer Ingelheim and has received lecture fees from GlaxoSmithKline, Roche, Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, Janssen-Cilag, Boehringer Ingelheim and Schering-Plough. All other authors: none to declare.

Ethical approval

The study was designed and performed according to the Helsinki declaration and was approved by the Ethics Committee of the Valme University Hospital (Seville, Spain).

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All patients gave their written informed consent before being included in the study.

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Neukam, K., Morano-Amado, L.E., Rivero-Juárez, A. et al. Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients. Eur J Clin Microbiol Infect Dis 36, 853–861 (2017). https://doi.org/10.1007/s10096-016-2871-x

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