RESUMO
INTRODUCTION AND OBJECTIVES: We examined whether Mac-2-binding protein glycosylation isomer (M2BPGi) levels could be a predictive marker for the presence of esophagogastric varices (EGV) in cirrhotic patients after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs). PATIENTS AND METHODS: A total of 102 cirrhotic patients with HCV infection treated with DAAs were enrolled. Esophagogastroduodenoscopy was performed in 84 of the patients before treatment (Cohort A), in 66 after treatment (Cohort B), and in 48 at both time points (Cohort C). We examined factors associated with EGV before and after DAA treatment. RESULTS: In Cohort A, M2BPGi levels and liver stiffness were significantly higher in the EGV-positive group than the EGV-negative group (p=0.034, and p=0.042, respectively). The proportion of EGV-positive patients with before-treatment levels of M2BPGi ⧠7.3 C.O.I. was significantly higher than in patients with M2BPGi levels<7.3 C.O.I. (p=0.015). In Cohort B, M2BPGi levels were significantly higher in the EGV-positive group than EGV-negative group (p=0.003). The proportion of EGV-positive patients with after-treatment levels of M2BPGi ⧠3.4 C.O.I. was significantly higher than in patients with M2BPGi levels<3.4C.O.I. (p=0.001). In Cohort C, M2BPGi levels decreased during DAA treatment regardless of EGV development, but there was no significant difference in the reduction of M2BPGi among the EGV-improvement, EGV-invariant, and EGV-exacerbation groups (p=0.659). CONCLUSIONS: M2BPGi levels may be a novel serum marker for the presence of EGV before and after DAA treatment.
Assuntos
Antígenos de Neoplasias/metabolismo , Antivirais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Varizes Esofágicas e Gástricas/metabolismo , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/metabolismo , Idoso , Idoso de 80 Anos ou mais , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/etiologia , Feminino , Glicosilação , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
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.
Assuntos
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
AIM: Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia and a sustained viral response (SVR) during combination therapy. MATERIAL AND METHODS: This study enrolled 62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment. At the occurrence of anemia (hemoglobin < 12 g/dL), the TVR-reduced group received 1500 mg TVR plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose (2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at 24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups. RESULTS: No differences in the proportion of patients who became HCV RNA-negative were detected between the TVR-standard and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80% at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not statistically significant). CONCLUSIONS: TVR dose adjustment could prevent anemia progression without weakening the anti-viral effect during triple therapy in HCV-patients.