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ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.
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Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Antivirais , Brasil/epidemiologia , Carcinoma Hepatocelular/tratamento farmacológico , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêuticoRESUMO
Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-ß indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-ß indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 µU/mL to 8.90 µU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.
Assuntos
Diabetes Mellitus , Hepatite C Crônica , Resistência à Insulina , Estado Pré-Diabético , Humanos , Antivirais/uso terapêutico , Antivirais/farmacologia , Hepatite C Crônica/tratamento farmacológico , Hepacivirus , Hemoglobinas Glicadas , Estado Pré-Diabético/tratamento farmacológico , Resistência à Insulina/fisiologia , Diabetes Mellitus/tratamento farmacológico , GlucoseRESUMO
BACKGROUND: Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy. METHODS: A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. RESULTS: SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. CONCLUSIONS: DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.
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Abstract INTRODUCTION: We compared the hepatitis C virus (HCV) core antigen test with the HCV RNA assay to confirm anti-HCV results to determine whether the HCV core antigen test could be used as an alternative confirmatory test to the HCV RNA test. METHODS: Sera from 156 patients were analyzed for anti-HCV and HCV core antigen using a chemiluminescent microparticle immunoassay (Architect i2000SR) and for HCV RNA using the artus HCV RG RT-PCR Kit (QIAGEN) in a Rotor-Gene Q instrument. RESULTS: The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 77.35%, 100%, 100%, and 89.38%, respectively. HCV core antigen levels showed a good correlation with those from HCV RNA quantification (r =0.872). However, 13 samples with a viral load of less than 4000 IU/mL were negative in the HCV core antigen assay. All gray-zone reactive samples were also RNA positive and were positive on repeat testing. CONCLUSIONS: The Architect HCV core antigen assay is highly specific and has an excellent positive predictive value. At the present level of sensitivity (77%), the study is still relevant in a low-income setting in which most of the HCV-positive patients would go undiagnosed, since HCV RNA testing is not available and/or not affordable. HCV core antigen testing can also help determine the true burden of infection in a population, considering the fact that almost 50% of the anti-HCV positive cases are negative for HCV RNA.
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Humanos , Hepatite C/diagnóstico , Hepacivirus/genética , RNA Viral , Sensibilidade e Especificidade , Antígenos da Hepatite C , Anticorpos Anti-Hepatite CRESUMO
La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.
Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.
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Antivirais/administração & dosagem , Hepatite C Crônica/epidemiologia , Fatores Etários , Antivirais/efeitos adversos , Criança , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , México/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , PrevalênciaRESUMO
Resumen La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.
Abstract Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.
Assuntos
Humanos , Feminino , Gravidez , Criança , Antivirais/administração & dosagem , Hepatite C Crônica/epidemiologia , Antivirais/efeitos adversos , Complicações Infecciosas na Gravidez/virologia , Prevalência , Fatores Etários , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , México/epidemiologiaRESUMO
Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.
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Humanos , Feminino , Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/administração & dosagem , Imidazóis/administração & dosagem , Resultado do Tratamento , Hepacivirus/genética , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Quimioterapia Combinada , Resposta Viral Sustentada , Genótipo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR). MATERIAL AND METHODS: A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy. The patients were treated with 100 mg asunaprevir twice daily plus 60 mg daclatasvir once daily for 24 weeks. The primary endpoint was SVR 24 weeks after completing treatment. In addition, we evaluated the improvement of liver function and development of HCC for 1 year from the end of treatment (EOT). RESULTS: The SVR24 rate was 96% (47/49) in the cirrhotic group and 96% (91/95) in the non-cirrhotic group (p = 0.69). During treatment, grade III/IV adverse events occurred more frequently in cirrhotic patients (10/49; 20.4%) than in non-cirrhotic patients (10/96; 10.4%) (p = 0.099). After EOT, alanine aminotransferase and AFP levels were significantly decreased in cirrhotic patients with SVR. In addition, serum levels of albumin and platelet counts were significantly increased. On the other hand, the rates of HCC recurrence (43%) and development (7.4%) were higher in cirrhotic patients than in the non-cirrhotic patients (12.5% and 1.1%, respectively). CONCLUSION: RAS-oriented asunaprevir/daclatasvir therapy has a strong anti-HCV effect in patients with HCV genotype 1b. However, careful management is necessary in patients with cirrhosis.
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Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Carbamatos , Carcinoma Hepatocelular/virologia , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Isoquinolinas/efeitos adversos , Japão , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Testes de Função Hepática , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Recuperação de Função Fisiológica , Fatores de Risco , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Proteínas não Estruturais Virais/genéticaRESUMO
BACKGROUND AND AIMS: We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS: Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS: Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS: nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.
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Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interferon-alfa/administração & dosagem , Antivirais/efeitos adversos , Astenia/induzido quimicamente , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/efeitos adversos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Projetos Piloto , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Retratamento , Ribavirina/administração & dosagem , Carga Viral/efeitos dos fármacosRESUMO
In this case, a new possible strategy for treatment of hepatitis C virus (HCV) relapsing patients is described. The target of anti-HCV therapy is sustained viral response, but strategies for improving sustained viral response in relapsing patients would be useful, and ribavirin is crucial for obtaining viral response. Six weeks of induction therapy with ribavirin were used to improve efficacy of standard combined antiviral therapy in a patient relapsing to standard therapy. In the present case, the patient had undergone a retreatment with the same regimen with the exception of the six-week induction period with ribavirin. Use of induction therapy with ribavirin in this case has allowed for a sustained viral response without prolonging the interferon exposure time in retreatment.
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Feminino , Humanos , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Quimioterapia Combinada , Recidiva , Proteínas Recombinantes/uso terapêuticoRESUMO
La adherencia o cumplimiento terapéutico es la realización del tratamiento de la hepatitis C con dosis suficientes de Interferon pegilado y Ribavirina durante el tiempo previsto, es decir 80% de las dosis inicialmente indicada, en el 80% del tiempo establecido. El objetivo de esta investigación fue determinar la adherencia al tratamiento en el grupo seleccionado, el cumplimiento de la terapia depende de varios factores que incluyen: paciente, efectos colaterales, personal médico y paramédico y todo aquello que impida reducir dosis o interrumpir la terapia. En este trabajo se revisaron 41 historias del archivo interno de la consulta de hígado del Hospital Miguel Pérez Carreño a quien se le indico tratamiento con Peg-Interferon y RBV por diagnostico de Hepatitis C, independientemente del genotipo. Se tomaron en cuenta los siguientes parámetros: sexo, edad, morbilidad asociada, efectos colaterales, motivo para suspender terapia, % de pacientes que culminaron tratamiento, etc. Se utilizo procesador Word y Excel, y análisis estadístico simple. El hallazgo primordial fue que aproximadamente solo el 29% culmino la terapia. La conclusión de esta revisión es entender la importancia de profundizar la relación médico-paciente y la conformación del equipo multidisciplinario como punto indispensable para lograr la adherencia al tratamiento y por ende una respuesta viral sostenida, objetivo primordial de la terapia.
Adherence or compliance to therapy is to apply the treatment for Hepatitis C, with the maximum dosage of Pegylated Interferon and Ribavirin along the foreseen period, i.e. 80% of the dosage initially prescribed during 80% of the established time. The completion of this objective depends on numerous factors: 1. Relating to Patients: a) patients education and understanding to realize the consequences of the disease and b) encouraging the patient to comply with the therapy. 2. Inherent to the treatment itself: a) appropriate management of adverse effects and b) drug tolerance of the patient. 3. Setting up a multidisciplinary team: medical doctor, nurse, psychologist, hematologist, etc. which positively influence the attitude of patient preventing dose reduction and drop-out of therapy. In this paper we reviewed 41 patients medical records from the internal archive of the Hepatic Department, Miguel Pérez Carreño Hospital. Those patients were treated with Peg-Interferon and RBV (Ribavirin) due to Hepatitis C diagnosis, independently on the genotype. The following parameters were taken into account: gender, age, associate morbidity, side effects, reasons for suspending therapy, % of patients who completed therapy, etc. Word processor and Excel were used and the simple statistical analysis. With the fundamental finding that, approximately, only the 29% of patients culminated the therapy. Reviewing this series allowed us to assess the importance of deepen the doctor-patient relationship, as well as setting up a multidisciplinary team, as an essential point in order to achieve the adherence to treatment and, therefore, a sustained viral response: the paramount objective of the therapy.