RESUMO
BACKGROUND AND AIM: IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. METHODS: This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed. RESULTS: IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CCâ IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype. CONCLUSIONS: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.
Assuntos
Genótipo , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , Adulto , Povo Asiático , Estudos de Coortes , DNA Viral/metabolismo , Determinação de Ponto Final , Previsões , Técnicas de Genotipagem , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Interferons , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Chronic hepatitis C (CHC) infection remains a significant health issue. Most patients are asymptomatic, but long term infection may cause liver failure, liver cancer, and death. Projections estimate that these complications will triple by 2020. Chronic hepatitis C infection is curable, and successful viral eradication reduces liver related complications. The landscape of CHC therapy is rapidly changing. OBJECTIVE: This article outlines the incidence, prevalence and natural history of CHC, and provides information that may assist the general practitioner in the assessment and management of CHC patients. DISCUSSION: Chronic hepatitis C infection is under-diagnosed and may lead to significant morbidity and mortality. Currently, only 1.3% of cases are being treated. The GP plays an important role in diagnosing CHC, and provides a unique opportunity to screen patients with risk factors and refer for treatment. The first direct-acting antivirals have recently been approved, and combination all-oral therapy (interferon free) is expected in 3-5 years. Hence, all patients with CHC should be referred for treatment consideration.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/epidemiologia , Austrália/epidemiologia , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Prevalência , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Carga ViralRESUMO
BACKGROUND AND AIM: Pegylated interferon-α (PEG-IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non-controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG-IFN-α2A in CHB patients in a clinical setting. METHODS: Chronic hepatitis B patients treated with PEG-IFN-α2A (180µg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA <351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion. RESULTS: Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post-treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50-75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs. CONCLUSION: In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.