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Aim: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain., Material and Methods: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded., Results: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin., Conclusions: Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV., Competing Interests: José Manuel Sousa has received fees as speaker from AbbVie, MSD and Gilead. Mercedes Vergara has received fees as an advisory board member from Gilead and has given lectures for AbbVie, Intercept, MSD, Janssen-Cilag and Gilead. Federico Pulido has received fees as speaker and advisor from AbbVie, Gilead, Janssen and MSD. Gloria Sánchez-Antolín has acted as speaker for AbbVie, MSD, Gilead Science, Novartis and Astellas. Diego Rincón has given lectures for AbbVie and MSD. Javier Salmerón has received speaker fees and grant funding from AbbVie; he declares no further conflict of interest. Luisa García-Buey has received speaker fees and travel grants from Abbvie, MSD and Gilead. José A. Carrión has received speaker fees from Abbvie, Gilead and MSD and has received fees as Advisor for AbbVie. Manuel Hernández-Guerra has been a consultant to Gilead Sciences, Intercept Pharmaceuticals, Abbvie and Bayer; he has received grant funding from Gilead Sciences and Abbvie. Nuria Espinosa has participated in Clinical Trials managed by Gilead and ViiV Healthcare; she has received advisory board, conference and course fees as well as expenses for attending congresses from Janssen-Cilag, Gilead Sciences, ViiV Healthcare, MSD and Abbvie. Rosa Mª Morillas has acted as a speaker for Gilead, Merck, AbbVie and Intercept, and has participated in advisory boards for AbbVie, Gilead and Intercept. Raul J. Andrade: Advisor/Speaker Bureau: Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen; Research Grants: Willmar Schwabe GmbH & Co, Gedeon Richter/Preglem S.A. Manuel Delgado has received scientific advisor fees from Abbie, Gilead, MSD. José M Moreno-Planas has received speaker fees from AbbVie, MSD, Gilead and Bayer. Fernando Menéndez has received fees as advisor from Bayer. Luis Morano has acted as speaker, advisor and/or investigator for Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen, Boehringer Ingelheim, Novartis, and Roche Farma. Manuel Rodríguez consults for and is on the speaker’s bureau for Gilead and AbbVie. Sara Lorente has received lecture fees from Abbvie, Gilead Sciences and MSD. Miguel Ángel Von-Wichmann has received fees as speaker and advisor from Abbvie, BMS, Gilead, Janssen, MSD and VIIV. Amanda Manzanares is employee of AbbVie and may hold stock or options. Lander Hijona, Fernando Carnicer, Beatriz Mateos-Muñoz, Antoni Jou, Benjamín Polo-Lorduy, Ángel Rubín, Ana Escarda, Patricia Aguilar, Teresa Aldámiz-Echevarría, Sonia Chimeno-Hernández, Adolfo Gallego, Marta Magaz, Ángel Estébanez, Mikel Rico, Blanca Sampedro, Sonia Izquierdo, José Manuel Zozaya, Senador Morán-Sánchez, Ignacio Martín-Granizo, Marcial Delgado declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C, including transplant recipients with an advanced fibrosis stage. Our aim in this study was to assess the clinical and functional benefits and improvement in liver fibrosis after treatment with DAAs in liver transplant recipients with chronic hepatitis C virus who achieved sustained virologic response (SVR)., Methods: We retrospectively analyzed 42 patients who underwent liver transplantation (LT) at our institution and were treated with DAAs from June 2014 to December 2015. Two patients died, so we ultimately included 40 transplant patients with chronic hepatitis C who received DAAs and achieved SVR. We assessed liver function, fibrosis stage, and clinical features at the start of the treatment, and then at 6 and 12 months after SVR. The indication for LT was hepatocellular carcinoma in 8 patients (20%) and Child-Pugh score B/C in 32 patients (80%)., Results: The DAAs regimens were sofosbuvir plus daclatasvir (45.0%), simeprevir plus sofosbuvir (42.5%), sofosbuvir plus ledipasvir (7.5%), and ombitasvir/paritaprevir/ritonavir (5%). The mean Modified End-stage Liver Disease (MELD) score pretreatment was 10.78, and was 8.46 at 1 year after treatment (P < .05). In addition, fibrosis stage decreased significantly from 14.81 kPa to 9.07 kPa (FibroScan) at 12 months after SVR. Clinically, there was a significant improvement, including control of ascites and chronic hepatic encephalopathy., Conclusion: DAAs were used successfully in the treatment of hepatitis C after orthotopic liver transplantation and resulted in significant improvement in liver function as measured by MELD score, fibrosis level, and cirrhotic clinical condition, even in patients with very advanced disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Rational: Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220)., Results: The mean patient age was 55 years, 67% male. Type of prior response was 22% naïve, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naïve patients (78%) compared with F3/F4-naïve patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001)., Conclusions: This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.

Introduction: Gene expression profiling in the first weeks of treatment of patients with chronic hepatitis C may contribute to better evaluate the response to interferon-based therapy. The objective of this study was to evaluate the gene expression profiles of early responders and non-responders before, and after 12 weeks of treatment with peginterferon alfa and ribavirin., Methods: Gene expression profiles were analysed in 12 patients with chronic hepatitis C, and scheduled for treatment with peginterferon alpha and ribavirin., Results: Of the 12 patients studied, six showed a complete early virological response, while six failed to control viremia. In early responders, treatment with peginterferon and ribavirin induced an increased expression of a larger number of interferon-induced genes (ISG15, IFI6, IFI44L, IFI27, MX1, OASL, IRF7, IFIT3, IFITM1, EIF2AK2, HERC5 and APOBEC3) than in non-responders (ISG15, IFI44L, IFI27, IRF7, USP18) in the first twelve weeks of treatment (P<0.05). In both groups, there were changes in the levels of certain genes poorly described in the treatment of hepatitis C so far., Conclusions: The gene expression profiles described in this study provide a new insight to understanding the pathogenesis of the disease and treatment effect. The more marked effect of the treatment on the expression of interferon-response genes observed in early responders could explain their better control of viral load., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Cases of red fingers syndrome and nodular vasculitis in patients with hepatitis C have rarely been described. Both red fingers syndrome and nodular vasculitis are characterized by microscopic vasculitis, and it has been hypothesized that hepatitis C plays a role in the pathogenesis of cutaneous disorders such as vasculitis, especially in cryoglobulinaemic vasculitis. We describe the case of a 75-year-old woman diagnosed with chronic hepatitis C who presented with nodular lesions on her right thigh and red fingers syndrome. A skin biopsy taken from a nodule showed infiltration of the vessel walls by mononuclear cells and septal and lobular panniculitis. The diagnosis of nodular vasculitis was established. In our opinion, red fingers syndrome and nodular vasculitis might be related to a vascular reaction of immune-mediated mechanisms induced by hepatitis C.