RESUMO
Objective: 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. Methods: 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. Results: 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]). Conclusions: The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Antivirais/uso terapêutico , Hepatite C/psicologia , Hepatite C/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Escalas de Graduação Psiquiátrica , Ribavirina/uso terapêutico , Espanha/epidemiologia , Fatores de Tempo , Modelos Logísticos , Incidência , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Hepatite C/epidemiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.
Assuntos
Antivirais/uso terapêutico , Transtorno Depressivo/epidemiologia , Hepatite C/tratamento farmacológico , Hepatite C/psicologia , Adulto , Idoso , Feminino , Hepatite C/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Ribavirina/uso terapêutico , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
ABSTRACT The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.
Assuntos
Humanos , Inibidores de Proteases/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/terapia , Prolina/análogos & derivados , Hepatite C/tratamento farmacológico , Simeprevir/efeitos adversos , Anemia Aplástica/induzido quimicamente , Anemia Aplástica/terapia , Índice de Gravidade de Doença , Exame de Medula Óssea , Prolina/efeitos adversos , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento , Hepatite C/diagnóstico , Evolução Fatal , Quimioterapia CombinadaRESUMO
The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.
Assuntos
Anemia Aplástica/induzido quimicamente , Antivirais/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Hepatite C/tratamento farmacológico , Prolina/análogos & derivados , Inibidores de Proteases/efeitos adversos , Simeprevir/efeitos adversos , Adulto , Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/terapia , Exame de Medula Óssea , Quimioterapia Combinada , Evolução Fatal , Hepatite C/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prolina/efeitos adversos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Interferons , Interleucinas/genética , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , RNA Viral/sangue , Fatores de Risco , Índice de Gravidade de Doença , Espanha , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed.