HEPATOLOGY Peginterferon alpha-2a and ribavirin in patients with hepatitis C virus genotype 1 infection with persistently normal alanine aminotransferase levels José-Luis Calleja,* Javier García-Samaniego, ‡ Belén Ruiz-Antorán, † María Trapero, § Rosa Morillas,** Juan de la Revilla,* José Carlos Erdozaín, ¶ María-Dolores Espinosa, †† Dolores Suárez, ‡‡ Ricard Solá, §§ Manuel Romero-Gómez, ¶¶ Fernando Baños,*** Marco-Antonio Álvarez ††† and for the Management of HCV Infection and Normal Transaminases Spanish Study Group 1 *Department of Gastroenterology and Hepatology, † Clinical Pharmacology Department, University Hospital Puerta de Hierro Mahadahonda Madrid, ‡ Liver Unit, Hospital Carlos III, CIBERehd, § Liver Unit, Department of Gastroenterology, University Hospital La Princesa, Institute of investigation La Princesa and CIBERehd, ¶ Department of Gastroenterology, University Hospital “Infanta Sofía,” Madrid, **Liver Unit, CIBERehd, Department of Gastroenterology, Germans Trias i Pujol University Hospital, Badalona, Badalona, †† Department of Gastroenterology, University Hospital Virgen de las Nieves, Granada, ‡‡ Department of Internal Medicine, Liver Unit, Complejo Hospitalario Arquitecto Marcide, Ferrol, §§ Liver Unit, Department of Gastroenterology, Hospital del Mar, Barcelona, ¶¶ Liver Unit, Hospital Nuestra Señora de Valme, CIBERehd, Sevilla, ***Department of Gastroenterology, Consorci Sanitari Integral, Hospital de L’Hospitalet, L’Hospitalet de Llobregat, and ††† Department of Gastroenterology, Althaia, Xarxa Assistencial de Manresa, Manresa, Spain Abstract Background and Aim: To evaluate the efficacy and safety of peginterferon a-2a plus ribavirin at standard doses in patients with hepatitis C virus (HVC) genotype 1 infection with persistently normal alanine aminotransferase (ALT) levels. Methods: Patients aged 18 to 65 years were included in this observational, prospective study if they had evidence of a HCV genotype 1 infection. The serum HCV RNA concen- tration was determined at baseline and week 12. A qualitative HCV RNA test was per- formed at baseline and at weeks 48 and 72. Liver function tests were performed at each study visit. The primary efficacy measure was the sustained virological response in the intention-to-treat population. Logistic regression analyses were also performed to explore predictors of virological response. Results: A sustained virological response was observed in 100 of the 175 patients (57%). An early virological response and end-of-treatment response were seen in 159 patients (91%) and 133 patients (76%), respectively. Thirty-seven of the 122 evaluable patients for this outcome (30%) showed a rapid virological response. A higher viral load was a significant predictor for a lack of rapid virological response and lack of sustained virologi- cal response. There were not any unexpected safety or tolerability findings. Conclusions: Our study suggests that the efficacy of the combination of peginterferon a-2a and ribavirin in patients with HCV genotype 1 infection and normal ALT levels is at least similar to that reported in patients with elevated ALT levels. Key words Hepatitis C, peginterferon, persistently normal alanine aminotransferase, ribavirin, sustained virological response. Accepted for publication 11 June 2012. Correspondence Dr José-Luis Calleja, Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, C/Manuel de Falla 1, 28222 Majadahonda, Madrid, Spain. Email: joseluis.calleja@uam.es 1 Management of HCV Infection and Normal Transaminases Spanish Study Group: Dr José Luis Calleja; Dra Belén Ruiz-Antorán; Dr J de la Revilla; Dr Javier García Samaniego; Dra Miriam Romero; Dra Angelica Moreno; Dra María Trapero; Dr Ramón Planas; Dra Rosa M a Morillas; Dr José Carlos Erdozaín; M a Dolores Espinosa; Dra Flor Nogueras; Dra Dolores Suárez; Dr Ricard Solá; Dra Lourdes Grande; Dr M. Romero-Gómez; Dr Fernando Baños; Dr Marco Antonio Álvarez; Dr José Antonio Pons; Dra Angeles Castro; Dr Javier Salmerón Escobar; Dr Luis Rodriguez; Dr Miguel Jiménez Pérez; Dra Mercedes Vergara Gómez; Dra Mireia Miguel Planas; Dra Emilia García; Dra María Moreno; Dr Francisco Jorquera; Dra Rosa Durández; Dr Senador Morán; Dra Pilar Castillo; Dr Pere Vaquer; Dra Lucía Bonet; Dra María Jesús Suárez; Dra Milagros Testillanc; Dr José M a Navarro; Dr P. Moreno Mejías; Dr José Aguilar; Dr Santiago Tomé; Dr Esteban Otero; Dr Agustín Domínguez; Dr Jaime Enríquez; Dr Adolfo Gallego Moya; Dr Jordi Ortiz; Dr Jaume Boadas; Dra Mercè Roget; Dra Mercé Barenys De Lacha; Dr Oscar Núñez; Dr Javier Rodríguez Gil; Dr Vicente Torrente González; Dr Manuel Miras; Dra Sonia Blanco Sampascual; Dr José Manuel González; Dr Fermín Santalla Reciña; Dr Raúl Andrade; Dr Ramón Barniol; Dr Miguel Torres; Dr Juan Carlos Quer; Dra Silvia Montoliu; Dr Benjamín Polo y Dr Manuel García Bengoechea. Authors’ declaration of personal interests: Dr Calleja has received fees for serving as an advisory board member for Roche, Gilead, MSD and Janssen. Dr García-Samaniengo has received fees for serving as a speaker and/or consultant for Roche, Gilead, MSD, BMS and Boehringer. Dr Solá has received fees for serving as an advisory board member for Roche, Gilead, MSD and BMS. Dr Romero has received fees for serving as a consultant and an advisory board member for Roche, Janssen, MSD, BMS and Boehringer. Dr Ruiz-Antorán, Dr, Trapero, Dr Morillas, Dr de la Revilla, Dr Erdozaín, Dr Espinosa, Dr Suarez, Dr Baños and Dr Alvarez have declared not having any conflict of interest within the last 3 years which may arise from being named as an author on this manuscript. doi:10.1111/j.1440-1746.2012.07214.x 1705 Journal of Gastroenterology and Hepatology 27 (2012) 1705–1710 © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd