RESUMO
We describe the genotypes and allele distribution of interleukin 28B (IL28B) rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in hepatitis C virus (HCV) G1-4 infected patients, to assess predictive ability and to determine whether the combined determination of two IL28B SNPs might improve sustained virologic response (SVR) prediction of both in HCV mono- and HIV/HCV co-infected patients. IL28B SNPs were genotyped in 269 patients, 181 mono- and 88 co-infected, treated with pegylated interferon and ribavirin. Data stratified by HCV mono- and HCV/HIV co-infected patients showed that 58% and 31% of the rs12979860CC carriers and 49% and 21% of the rs8099917TT carriers had SVR. IL28B SNPs, HCV mono-infection and HCV RNA load were associated with SVR as independent predictors in the two study groups as a whole. ROC curve analyses in the two populations separately, based on gender, age, baseline HCV RNA load and rs12979860/rs8099917 revealed similar receiver operating characteristics (ROC) areas under the curve values. Combining the determination of IL28B SNPs, rs8099917 genotyping improved the response prediction in rs12979860CT carriers only in mono-infected patients. In the era of direct-acting antiviral agents, adopting SVR baseline predictors to orientate naïve-patient management represents an important issue. A model involving IL28B SNPs appears able to predict SVR in both populations.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Coinfecção/tratamento farmacológico , Coinfecção/genética , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , HIV-1/fisiologia , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepacivirus/fisiologia , Hepatite C/genética , Hepatite C/virologia , Humanos , Interferon-alfa/uso terapêutico , Interferons , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in "real world" chronic hepatitis C patients in Italy. METHODS: Independent observational multicentre study including consecutive patients receiving Peg-interferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. RESULTS: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and γ-glutamil-transpeptidase >2 times the normal limit were associated with poorer response. CONCLUSIONS: The response to Peg-interferon/ribavirin therapy in "real world" clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-to-treat than among difficult-to-treat hepatitis C virus genotypes.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Sistema de Registros , Ribavirina/uso terapêutico , Antivirais/uso terapêutico , Portadores de Fármacos , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Hepatite C Crônica/virologia , Vírus de Hepatite/genética , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/análise , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non-infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty-five patients (71% male) were evaluated. Their median age was 48 years (range 5-84), and 83.4% were of Italian origin. Community-acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion-associated transmission (1.8%). Hepatitis B e-antigen was present in 20.4% of the patients, while co-infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir-dipivoxil. Forty-nine patients were co-infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Antígenos E da Hepatite B/sangue , Hepatite C/epidemiologia , Hepatite D/epidemiologia , Humanos , Itália/epidemiologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Between 350 and 400 million people worldwide have chronic hepatitis B virus (HBV) infection, and in Italy this figure is 1% to 2% in the general population. In clinical practice, however, it is not known how many patients chronically infected by HBV and eligible for antiviral therapy are not treated. AIM: To characterize the clinical picture of untreated HBV patients, and to assess whether current experts' recommendations for treatment are actually applied. METHODS: We evaluated 362 patients chronically infected by HBV alone who were followed for at least 1 year at tertiary referral centers in Liguria region, Italy. Patients' data were evaluated on the basis of the Panel of Experts algorithm for the management of HBV [ie, HBV DNA levels > or =20,000 IU/mL in hepatitis B e antigen (HBeAg)-positive patients, HBV DNA levels > or =2000 IU/mL in HBeAg-negative patients, and evidence of biochemical and/or histologic activity of disease in both groups]. RESULTS: One-hundred and sixteen viremic chronic hepatitis B disease patients were not on antiviral therapy (33 HBeAg positive, 83 HBeAg negative). Serum HBV DNA was > or =20,000 IU/mL and > or =2000 IU/mL in 32 HBeAg-positive and 54 HBeAg-negative patients, respectively, and disease was present in 59 of these 86 patients. Treatment was not indicated in 10 of 59 patients, and had been planned in 8 (4 HBeAg positive), thus 84% potential treatment candidates (41 of 49 patients) were not treated. CONCLUSIONS: Evaluation of a large series of patients chronically infected by HBV alone identified a significant proportion of patients who are actually untreated despite being potential candidates for antiviral therapy.