Incidence of depression in patients with hepatitis C treated with direct-acting antivirals

Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs. The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment. The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p > 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]). The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors

A Metabolomics Signature Linked To Liver Fibrosis In The Serum Of Transplanted Hepatitis C Patients

Liver fibrosis must be evaluated in patients with hepatitis C virus (HCV) after liver transplantation because its severity affects their prognosis and the recurrence of HCV. Since invasive biopsy is still the gold standard to identify patients at risk of graft loss from rapid fibrosis progression, it becomes crucial the development of new accurate, non-invasive methods that allow repetitive examination of the patients. Therefore, we have developed a non-invasive, accurate model to distinguish those patients with different liver fibrosis stages. Two hundred and three patients with HCV were histologically classified (METAVIR) into five categories of fibrosis one year after liver transplantation. In this cross-sectional study, patients at fibrosis stages F0-F1 (n = 134) were categorised as "slow fibrosers" and F2-F4 (n = 69) as "rapid fibrosers". Chloroform/methanol serum extracts were analysed by reverse ultra-high performance liquid chromatography coupled to mass spectrometry. A diagnostic model was built through linear discriminant analyses. An algorithm consisting of two sphingomyelins and two phosphatidylcholines accurately classifies rapid and slow fibrosers after transplantation. The proposed model yielded an AUROC of 0.92, 71% sensitivity, 85% specificity, and 84% accuracy. Moreover, specific bile acids and sphingomyelins increased notably along with liver fibrosis severity, differentiating between rapid and slow fibrosers

Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications

Effectiveness of hepatitis C antiviral treatment in attended patients from the outpatient pharmacy consultation

Objetivos: Determinar la efectividad del tratamiento de la hepatitis C crónica definida como la respuesta viral sostenida a las 12 semanas (RVS12) tras la finalización del tratamiento con fármacos antivirales de acción directa (AAD) (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir y grazoprevir/elbasvir) en pacientes atendidos en la consulta de farmacia ambulatoria. Métodos: estudio retrospectivo que incluye los pacientes atendidos por farmacia que iniciaron tratamiento con AAD entre el 1 de diciembre de 2017 y el 31 de mayo de 2018. Se registraron datos demográficos, de la enfermedad, grado de adherencia y consultas sobre el tratamiento (interacciones, efectos adversos y otras). Resultados: Se incluyeron 205 pacientes con diferentes genotipos de hepatitis C, estados de fibrosis y grados de morbilidad. La efectividad fue del 99,5%, similar a la reportada en los ensayos clínicos. Conclusiones: Estos resultados se asemejan a los obtenidos en las consultas de farmacia en Estados Unidos, funcionando desde hace más de diez años.Objective: To determine the effectiveness of the treatment of chronic hepatitis C determined as the sustained viral response at 12 weeks (SVR12) after the end of treatment with direct-acting antiviral drugs (DAA) (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir and grazoprevir/elbasvir) in attended patients from the outpatient pharmacy consultation. Method: a retrospective study that includes patients attended by pharmacists who started treatment between December 1, 2017 and May 31, 2018. Demographic data, disease, adherence and treatment consultations were recorded (interactions, adverse effects and others). Results: Two hundred and five patients were included, with different hepatitis C genotypes, fibrosis states and morbidity levels. Effectiveness was 99.5%, similar to that of clinical trials. Conclusions: These results resemble those obtained in pharmacy consultations in the United States, operating for more than ten years

Efectividad del tratamiento de la hepatitis C en pacientes atendidos en la consulta de atención farmacéutica

Objective: To determine the effectiveness of the treatment of chronic hepatitis C determined as the sustained viral response at 12 weeks (SVR12) after the end of treatment with direct-acting antiviral drugs (DAA) (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir and grazoprevir/elbasvir) in attended patients from the outpatient pharmacy consultation.Method: a retrospective study that includes patients attended by pharmacists who started treatment between December 1, 2017 and May 31, 2018. Demographic data, disease, adherence and treatment consultations were recorded (interactions, adverse effects and others).Results: Two hundred and five patients were included, with different hepatitis C genotypes, fibrosisstates and morbidity levels. Effectiveness was 99.5%, similar to that of clinical trials.Conclusions: These results resemble those obtained in pharmacy consultations in the United States,operating for more than ten years.Introducción: el presente estudio tiene como objetivo determinar la efectividad del tratamiento de la hepatitis C crónica definida como la respuesta viral sostenida a las 12 semanas (RVS12) tras la finalización del tratamiento con fármacos antivirales de acción directa (AAD) (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir y grazoprevir/elbasvir) en pacientes controlados desde la consulta de farmacia ambulatoria.Método: estudio retrospectivo que incluye los pacientes atendidos por farmacia que iniciaron tratamiento con AAD entre el 1 de diciembre de 2017 y el 31 de mayo de 2018. Se registraron datos demográficos, de la enfermedad, grado de adherencia y consultas sobre el tratamiento (interacciones, efectos adversos y otras).Resultados: se incluyeron 205 pacientes, con diferentes genotipos de hepatitis C, estados de fibrosis y grados de morbilidad. La efectividad fue del 99,5%, similar a la reportada en los ensayos clínicos.Conclusiones: estos resultados  se asemejan a los obtenidos en las consultas de farmacia en Estados Unidos, funcionando desde hace más de diez años

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE‐associated discontinuation events occurred in 5.9% and 2.6%. Conclusions. In this large cohort of cirrhotic patients managed in the real‐world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.Instituto de Salud Carlos III; PI15/0015

High efficacy and tolerability of hepatitis C genotype 2 treatment with direct-acting antivirals in real world: analysis of the Hepa-C Registry

Poster presentatio

Safety and Efficacy of Sofosbuvir plus Simeprevir in a Spanish Cohort of 622 Cirrhotic Patients Infected with Genotypes 1 or 4

Presentation Poste