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PURPOSE: Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB. MATERIALS AND METHODS: A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168. RESULTS: Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively. CONCLUSION: The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Detecção Precoce de Câncer/métodos , Testes Genéticos , Hepatite B Crônica/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , RNA Neoplásico/genética , Adulto , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Hepatite B Crônica/diagnóstico , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Malásia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , RNA Neoplásico/sangue , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND & AIMS: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. METHODS: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5µg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0µg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5µg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800-1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). RESULTS: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. CONCLUSIONS: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5µg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment.
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Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Peso Corporal , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/etnologia , Humanos , Análise de Intenção de Tratamento , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Recidiva , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND/AIMS: A large amount of new data on the treatment of chronic hepatitis B has become available such that the 2003 consensus statement requires revision and update. METHODS: New data were presented, discussed and debated in an expert pre-meeting to draft a revision. The revised contents were finalized after discussion in a general meeting of APASL. RESULTS: Conceptual background, including the efficacy and safety profile of currently available and emerging drugs, was reviewed. Nineteen recommendations were formed and unresolved issues and areas for further study were suggested. CONCLUSION: The current therapy of chronic hepatitis B is modestly effective but not satisfactory. The development of new drugs and new strategies is required to further improve the outcomes of treatment.