Prevalência de comorbidades, comedicações e interações medicamentosas com agentes antivirais diretos orais em pacientes com infecção pelo vírus da hepatite C crônica

Introdução e objetivo: Comorbidades (CMOR) e comedicações (CMED) são comuns em pacientes com hepatite C (HCV) podendo resultar em interações medicamentosas (DDIs) de risco. O objetivo deste estudo foi avaliar a prevalência de CMOR, CMED e DDIs com agentes antivirais diretos (DAAs) nesta população. Método: CMOR e CMED foram avaliadas em uma coorte retrospectiva de pacientes com hepatite C. As DDIs, de acordo com as CMED, foram estimadas com os seguintes esquemas: telaprevir (TVR); sofosbuvir (SOF)/simeprevir (SMV), SOF/daclatasvir (DCV), SOF/ledipasvir (LDV), SOF/velpatasvir (VEL), elbasvir (EBR)/ grazoprevir (GZR), ombitasvir/paritaprevir/ritonavir (2D) e 2D/dasabuvir (3D); glecaprevir (GLE)/pibrentasvir (PIB) e SOF/VEL/voxilaprevir (VOX). As interações foram avaliadas de acordo com a base de dados da Universidade de Liverpool. Resultados: Foram avaliados os dados de 1433 pacientes com HCV. A média de idade foi de 51,7 anos (DP±10,7) e 50,6% dos pacientes eram do sexo feminino. DAAs foram prescritos para 345 (24,1%) dos pacientes e 264 (76,5%) atingiram resposta virológica sustentada. A média de CMOR foi de 1,5±1,27 por paciente. A média de CMED foi de 3,16± 2,67 medicamentos por paciente. Foram encontradas 12916 DDIs, sendo 1.859 (14,4%) de alto risco - média de 1,29± 3,13 por paciente. O esquema 3D, além de GLE/PIB e SOF/VEL/VOX, apresentou os maiores índices de DDIs. Conclusão: CMOR e CMED são frequentes em pacientes com HCV e as DDIs são comuns. Mesmo com os fármacos de segunda geração as DDIs continuarão a apresentar risco significativo.Introduction and aim: Comorbidities (CMOR) and comedications (CMED) are common in patients with hepatitis C (HCV), which may result in risky drug interactions (DDIs). The objective of this study was to evaluate the prevalence of CMOR, CMED and DDIs with direct antiviral agents (DAAs) in this population. Method: CMOR and CMED were evaluated in a retrospective cohort of HCV patients. The DDIs, according to the CMED, were estimated with the following drug schemes: telaprevir (TVR); elbasvir (EBR)/grazoprevir (GZR), ombitasvir/paritaprevir/ritonavir (2D), and sofosbuvir (SOF)/simeprevir (SMV), SOF/daclatasvir (DCV), SOF/ledipasvir 2D/dasabuvir (3D); glecaprevir (GLE)/pibrentasvir (PIB) and SOF/VEL/voxilaprevir (VOX). The interactions were evaluated according to the University of Liverpool database. Results: Data from 1433 patients with HCV were evaluated. The mean age was 51.7 years (SD ± 10.7) and 50.6% of the patients were female. DAAs were prescribed for 345 (24.1%) patients and 264 (76.5%) achieved sustained virological response. The main CMORs were systemic arterial hypertension [436 (30.4%)], diabetes mellitus [352 (24.6%)] and depression [130 (9.1%)]. The mean CMOR was 1.5 ± 1.27 per patient. The mean CMED was 3.16 ± 2.67 medications per patient. A total of 12916 DDIs were found, of which 1,859 (14.4%) were high risk - mean of 1.29 ± 3.13 per patient. The 3D scheme, besides GLE/PIB and SOF/VEL/VOX, presented the highest indexes of DDIs. Conclusion: CMOR and CMED are common in patients with HCV and DDIs are common. Even with the use of second generation drugs, the occurrence of DDIs remains presenting a significant risk

Avaliação dos fatores relacionados à hepatotoxicidade, em pacientes internados com alteração das enzimas hepáticas, sob a ótica da farmacovigilância

Introdução: A lesão hepática induzida por medicamentos (DILI) é uma reação adversa rara, relacionada à hepatotoxicidade. A notificação pós comercialização ocorre pelo sistema de farmacovigilância, que adota algoritmos de causalidade como Naranjo e Rucam. Objetivo: Compreender a relação de transaminases (ALT) \u3e 5 vezes o limite da normalidade (\u3e5xLSN) com EA associados a DILI e verificar a frequência de relatos ao sistema de farmacovigilância do hospital e do VIGIMED para propor estudo de farmacovigilância ativa (aprovado pelo CEP). Método: Coorte retrospectiva, obtida de prontuários médicos de pacientes internados em 2018 que apresentaram alteração de ALT \u3e 5xLSN. Resultado: Em 2018 encontramos 597 internados com elevação de ALT, 11 deles com transplante hepático. Tratados por diferentes especialidades, 4,7%/n=28 apresentaram níveis acima de 5xLSN. Destes, 67,8%/n=19 foram a óbito com prevalência do CID A41.9 Septicemia não especificada (p\u3c0,001). Entre os medicamentos prescritos 57,1% representavam potencial de hepatotoxicidade, como antibióticos cefepime (21,4%) e Amoxicilina + clavulanato (7,1%). Nos dados do Vigimed em 2018 foram relatados 117 eventos adversos (EA), 62,39% (n=73) graves e 0,85% (n=1) com óbito. O relato de aumento das transaminases foi de 0,85% (n=1). Sintomas comuns de DILI foram relatadas: prurido 17,85%(n=21) e erupção cutânea 4,27%(n=5). Não há relato de EA descrito como DILI. Conclusão: A farmacovigilância ativa pode identificar EA associados à DILI pelas alterações nas transaminases. O êxito da investigação da causalidade e do diagnóstico depende da avaliação de risco, adoção de algoritmos de causalidade adequados, monitoramento das enzimas hepáticas e de possíveis biomarcadores

Prevalência de comorbidades, comedicações e interações medicamentosas com agentes antivirais diretos orais em pacientes com infecção pelo vírus da hepatite C crônica

Introdução e objetivo: Comorbidades (CMOR) e comedicações (CMED) são comuns em pacientes com hepatite C (HCV) podendo resultar em interações medicamentosas (DDIs) de risco. O objetivo deste estudo foi avaliar a prevalência de CMOR, CMED e DDIs com agentes antivirais diretos (DAAs) nesta população. Método: CMOR e CMED foram avaliadas em uma coorte retrospectiva de pacientes com hepatite C. As DDIs, de acordo com as CMED, foram estimadas com os seguintes esquemas: telaprevir (TVR); sofosbuvir (SOF)/simeprevir (SMV), SOF/daclatasvir (DCV), SOF/ledipasvir (LDV), SOF/velpatasvir (VEL), elbasvir (EBR)/ grazoprevir (GZR), ombitasvir/paritaprevir/ritonavir (2D) e 2D/dasabuvir (3D); glecaprevir (GLE)/pibrentasvir (PIB) e SOF/VEL/voxilaprevir (VOX). As interações foram avaliadas de acordo com a base de dados da Universidade de Liverpool. Resultados: Foram avaliados os dados de 1433 pacientes com HCV. A média de idade foi de 51,7 anos (DP±10,7) e 50,6% dos pacientes eram do sexo feminino. DAAs foram prescritos para 345 (24,1%) dos pacientes e 264 (76,5%) atingiram resposta virológica sustentada. A média de CMOR foi de 1,5±1,27 por paciente. A média de CMED foi de 3,16± 2,67 medicamentos por paciente. Foram encontradas 12916 DDIs, sendo 1.859 (14,4%) de alto risco - média de 1,29± 3,13 por paciente. O esquema 3D, além de GLE/PIB e SOF/VEL/VOX, apresentou os maiores índices de DDIs. Conclusão: CMOR e CMED são frequentes em pacientes com HCV e as DDIs são comuns. Mesmo com os fármacos de segunda geração as DDIs continuarão a apresentar risco significativo.Introduction and aim: Comorbidities (CMOR) and comedications (CMED) are common in patients with hepatitis C (HCV), which may result in risky drug interactions (DDIs). The objective of this study was to evaluate the prevalence of CMOR, CMED and DDIs with direct antiviral agents (DAAs) in this population. Method: CMOR and CMED were evaluated in a retrospective cohort of HCV patients. The DDIs, according to the CMED, were estimated with the following drug schemes: telaprevir (TVR); elbasvir (EBR)/grazoprevir (GZR), ombitasvir/paritaprevir/ritonavir (2D), and sofosbuvir (SOF)/simeprevir (SMV), SOF/daclatasvir (DCV), SOF/ledipasvir 2D/dasabuvir (3D); glecaprevir (GLE)/pibrentasvir (PIB) and SOF/VEL/voxilaprevir (VOX). The interactions were evaluated according to the University of Liverpool database. Results: Data from 1433 patients with HCV were evaluated. The mean age was 51.7 years (SD ± 10.7) and 50.6% of the patients were female. DAAs were prescribed for 345 (24.1%) patients and 264 (76.5%) achieved sustained virological response. The main CMORs were systemic arterial hypertension [436 (30.4%)], diabetes mellitus [352 (24.6%)] and depression [130 (9.1%)]. The mean CMOR was 1.5 ± 1.27 per patient. The mean CMED was 3.16 ± 2.67 medications per patient. A total of 12916 DDIs were found, of which 1,859 (14.4%) were high risk - mean of 1.29 ± 3.13 per patient. The 3D scheme, besides GLE/PIB and SOF/VEL/VOX, presented the highest indexes of DDIs. Conclusion: CMOR and CMED are common in patients with HCV and DDIs are common. Even with the use of second generation drugs, the occurrence of DDIs remains presenting a significant risk

Correction: Direct antiviral agents for hepatitis C and drug interaction risk: A retrospective cohort study with real and simulated data on medication interaction, prevalence of comorbidities and comedications.

[This corrects the article DOI: 10.1371/journal.pone.0245767.]

Direct antiviral agents for hepatitis C and drug interaction risk: A retrospective cohort study with real and simulated data on medication interaction, prevalence of comorbidities and comedications.

Introduction and aimComorbidities and comedication are common in patients with hepatitis C, which could result in a risk of drug-drug interaction. The objective of this study was to evaluate the prevalence of comorbidities, comedication and drug-drug interactions involving direct-acting antivirals in this population.MethodsComorbidities and comedications were evaluated in a retrospective cohort of hepatitis C patients. Drug-drug interactions were estimated in real life and with simulated data on comedications following drug regimens: telaprevir; elbasvir/grazoprevir, ombitasvir/paritaprevir/r/ritonavir (2D regimen), and sofosbuvir/simeprevir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir; 2D/dasabuvir (3D regimen); glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. The interactions were evaluated according to the University of Liverpool database. Statistical analysis was performed by SPSS® 18.0.ResultsData from 1433 patients with hepatitis C were evaluated. The mean patient age was 51.7 years (SD ± 10.7), and 50.6% were female. Direct-acting antivirals were prescribed for 345 (24.1%) patients, and a sustained virological response occurred in 264 (76.5%). The main comorbidities were systemic arterial hypertension [436 (30.4%)], diabetes mellitus [352 (24.6%)] and depression [130 (9.1%)]. The mean number of comorbidities was 1.52 (median [IQR] of 1.00 [1.00-2.00]). The mean number of comedications was 3.16 (median [IQR] of 3.00 [1.00-5.00]). A total of 12916 drug-drug interactions were found, of which 1.859 (14.4%) were high risk, with a mean of 1.29 ± 3.13 per patient. The 3D regimen, as well as glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir, presented the highest drug-drug interaction indexes.ConclusionComorbidities and comedications are common in patients with hepatitis C, as are drug-drug interactions. Even when second generation drugs are used, the occurrence of drug-drug interactions still presents a significant risk

Clinical and epidemiological profile of genotype 3 HCV patients in the South of Brazil

Introduction and aim. Despite the emergence of new treatments for genotype 3 HCV (G3 HCV), there is still a lack of data about this particular subgroup in Brazil. We aimed to describe clinical and sociodemographic variables and treatment profile of G3 HCV Brazilian patients. Methods. This was a descriptive, retrospective study, performed in a specialized center for HCV treatment in Brazilian South Region. Medical charts of patients diagnosed with G3 HCV were reviewed to collect clinical, sociodemographic and treatment information. Results. 564 subjects were enrolled, with mean age of 59.3 years (SD=10.5). Cirrhosis was present in 54.4% of patients. Most common co-existent conditions were systemic arterial hypertension (36.6%) and diabetes mellitus (30.0%). Regarding treatment, 25.2% of patients were treatment-naïve and 74.8% were currently treating (11.6%) or had received a previous treatment (87.0%). The most frequent ongoing treatment was sofosbuvir+daclatasvir(± ribavirin) (87.8%). Of the 388 patients who had at least one previous treatment, 67.0% achieved sustained virologic response in the last treatment. Caucasian/white, non-obese, transplanted patients, those with longer time since diagnosis and with cirrhosis were more likely to receive treatment, according to multivariate analysis. Patients with hepatocellular carcinoma had 64.1% less chance to be on treatment during the study period than those without this condition; patients with chronic kidney disease presents were 2.91-fold more likely to have a treatment interruption than those without. Conclusion. This study describes a large sample of Brazilian patients with G3 HCV. Treatment patterns were mainly influenced by presence of HCV complications and comorbidities