RESUMEN
BACKGROUND AND AIM: Patients with genotype 4 (G4) chronic hepatitis C (CHC) are considered a difficult to treat population, although current data on G4 treatment responsiveness and duration are controversial. Greece represents a country with an intermediate prevalence of G4 infections, offering an opportunity to compare treatment outcomes by genotype and to identify potential prognostic factors for sustained virologic response (SVR). METHODS: All CHC patients from the HepNet.Greece, an ongoing nationwide cohort study on viral hepatitis, with known hepatitis C virus (HCV) genotype who received treatment with Peg-IFNa and ribavirin were analyzed. RESULTS: From 4443 patients, 951 (61.7% males, 78.4% Greeks, median age 40.6 years, 10% cirrhosis) fulfilled the inclusion criteria. G4 was found in 125 (13.1%) patients. Genotype distribution was not significantly different between Greeks and immigrants. Patients with G4 had similar odds of SVR compared to G1 but significantly lower compared to G2/G3. Age, treatment discontinuation, presence of cirrhosis and previous history of HCV-treatment were associated with lower probabilities of SVR. Ethnicity did not affect SVR for all genotypes while response to treatment was similar between Greek and Egyptian patients groups (35.7% vs 40.9%, p=0.660%) with G4 infection. The relation between SVR and genotype did not substantially change after adjustment for age, gender, cirrhosis, treatment interruption and history of HCV-treatment. CONCLUSIONS: The findings of this large cohort of CHC patients with a well balanced genotype distribution further supports the idea of considering G4 as a difficult to treat genotype. Further investigation is needed to identify genotype specific prognostic factors.
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Preoperative systemic chemotherapy is generally applied in patients who undergo hepatic resection for colorectal metastases. Although the tumour response rate has been improved recently with the development of new molecular targeted therapies the related hepatic injury is ill defined. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor. It can achieve high response rates and is accepted as a first line treatment in the metastatic colorectal disease. However, the data about its hepatotoxicity profile is still limited. We describe a case of secondary sclerosing cholangitis in a patient with liver metastases treated by Bevacizumab in the neoadjuvant setting and liver resection. It is possible that Bevacizumab may have induced a hypercoagulative condition that was further precipitated by surgery.
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Adenocarcinoma/secundario , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Colangitis Esclerosante/inducido químicamente , Neoplasias Hepáticas/secundario , Neoplasias del Colon Sigmoide/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Anciano , Alanina Transaminasa/sangre , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Aspartato Aminotransferasas/sangre , Bevacizumab , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Colangitis Esclerosante/diagnóstico , Hepatectomía/efectos adversos , Humanos , Hígado/patología , Hígado/cirugía , Pruebas de Función Hepática , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Terapia Neoadyuvante/efectos adversos , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: Two-thirds of the 350 million people infected with chronic hepatitis B virus live in the Asia-Pacific region. AIM To compare the effects of adefovir dipivoxil therapy between Asian and Caucasian patients with chronic hepatitis B. METHODS: The safety and efficacy of 10 mg of adefovir dipivoxil was compared to placebo in 501 Asian (n = 259) or Caucasian (n = 242) HBeAg+ and HBeAg- chronic hepatitis B virus patients treated for 48 weeks in two randomized, double-blind, placebo-controlled studies. RESULTS: At week 48, histological improvement was observed in 60% and 56% of Caucasian and Asian patients, respectively. Change in serum hepatitis B virus DNA from baseline to week 48 for the adefovir dipivoxil-treated patients was -3.89 and -3.70 log(10) copies/mL in Caucasian and Asian patients, respectively, while 34 per cent of Caucasian patients and 39 per cent of Asian patients had undetectable serum hepatitis B virus DNA (<400 copies/mL) at week 48. The percentage of patients achieving alanine aminotransferase (ALT) normalization at week 48 was similar in both groups (Caucasian 64 per cent, Asian 63 per cent). No patients developed resistance through week 48. No differences in adverse events or grade 3 or 4 laboratory abnormalities were observed between groups. CONCLUSIONS: There were no significant differences in treatment response between Asians and Caucasians. Adefovir dipivoxil was well tolerated and no resistance developed up to week 48 in both racial groups.
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Adenina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/farmacología , Adenina/uso terapéutico , Adulto , Antivirales/farmacología , Pueblo Asiatico , Método Doble Ciego , Esquema de Medicación , Femenino , Hepatitis B Crónica/metabolismo , Humanos , Masculino , Organofosfonatos/farmacología , Placebos , Análisis de Regresión , Resultado del Tratamiento , Población BlancaRESUMEN
BACKGROUND AND OBJECTIVES: The Procleix Ultrio human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV)/hepatitis B virus (HBV) (Ultrio) assay simultaneously detects HIV-1 RNA, HCV RNA and HBV DNA in individual blood donations. The main objective of the study was to assess the analytical and clinical sensitivity of the multiplex and discriminatory probe assays in samples with a low viral load. MATERIAL AND METHODS: The VQC HIV RNA genotype B, HCV RNA genotype 1 and HBV DNA genotype A standard dilutions were tested in 26 repeats. The probability of detection by Ultrio was compared with previously obtained data of the Procleix Duplex HIV-1/HCV assay on the same reference panels. A selection of 121 anti-HIV-1, 138 anti-HCV and 190 HBsAg positive samples from patients receiving antiviral therapy were tested. The majority of patient samples had a viral load below the detection limit of the diagnostic nucleic acid test assays, which made them suitable to evaluate the performance of the multiplex and discriminatory assays on yield cases with a similar low viral load. RESULTS: The 95% and 50% detection end-points of the Ultrio assay along with the corresponding 95% confidence intervals are 53.7 (32.9-117.2) and 8.6 (6.2-12.1) geq/ml for HIV-1 RNA, 30.3 (19.0-62.4) and 5.2 (3.7-7.2) geq/ml for HCV RNA and 393.7 (147.9-6978) and 54.5 (22.4-143.8) geq/ml for HBV DNA. The analytical sensitivity of Ultrio expressed as a potency factor relative to previously obtained Duplex results on the same HIV-1 RNA and HCV-RNA standard dilutions was 1.09 (0.20-6.10) and 1.11 (0.21-5.89), respectively. The assay detected all 22 HIV-1 infected patients with viral load > 50 copies/ml, and 41 of 99 patients (41%) with viral load < 50 copies/ml, of which 23 (56%) were detected by the discriminatory assay. All 47 patients with HCV RNA load > 521 IU/ml and 10/91 polymerase chain reaction-negative patients with viral load < 50 IU/ml tested positive in Ultrio assay of which five were missed in the discriminatory test. The assay detected 53/55 HBV infected patients (96%) with viral load > 250 copies/ml and 108/135 patients (80%) with viral load < 250 copies/ml of which 17 (16%) were missed by the discriminatory test. CONCLUSIONS: The new Procleix Ultrio assay is as sensitive as the Procleix Duplex assay for HIV-1 and HCV detection meeting the requirements of universal guidelines. The ability of the assay to detect HBV DNA in low viral load samples could be useful for screening blood. Inevitable negative results of discriminatory probe assays caused by stochastic sample variation will reduce the chance of recognizing low viraemic blood donors detected by individual donation nucleic acid test.
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Donantes de Sangre , Infecciones por VIH/diagnóstico , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Pruebas Serológicas/métodos , Carga Viral , Infecciones por VIH/sangre , VIH-1/genética , VIH-1/aislamiento & purificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/sangre , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Development of organ- and non-organ-specific autoantibodies has been reported in hepatitis C virus patients treated with interferon-alpha plus/minus ribavirin. AIMS: To address whether prevalence and the titre of gastric parietal autoantibodies and non-organ-specific autoantibody in hepatitis C virus-treated patients were affected by therapy, and if the development of these antibodies carries any clinical significance on the response to treatment, as few studies in adults have been strictly designed to address the above hypothesis. METHODS: Samples at three time-points (baseline, end of treatment, end of follow-up) from 102 hepatitis C virus patients (39 sustained responders, 26 relapsers, 33 non-responders; four lost in follow-up) were studied for gastric parietal autoantibodies and/or non-organ-specific autoantibody by indirect immunofluorescence, commercial and in-house enzyme-linked immunosorbent assays. RESULTS: Sustained virological and biochemical response was associated with antinuclear antibody absence (end of treatment or end of follow-up), decrease of smooth-muscle antibody titres during therapy and gastric parietal autoantibodies negativity at baseline. However, after multivariate analysis only antinuclear antibody positivity at the end of treatment and increase of smooth-muscle antibody titres were associated with worst treatment response, independently of known factors of worst treatment outcome. CONCLUSIONS: We were able to demonstrate a negative correlation between the efficacy of anti-viral treatment for hepatitis C virus and the presence of antinuclear antibody and smooth-muscle antibody before treatment, or their increase during therapy.
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Antivirales/uso terapéutico , Autoanticuerpos/inmunología , Autoinmunidad/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Autoanticuerpos/fisiología , Autoinmunidad/fisiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
This study aimed to estimate the overall HCV genotype distribution and to reconstruct the HCV genotype-specific incidence in Greece during the recent decades. It also focused at the identification of genotype 4 subtype variability in Greek isolates. A total of 1686 chronically infected HCV patients with detectable serum HCV RNA by RT-PCR, belonging to different risk groups were studied. Amplified products from the 5'-noncoding region were typed using a commercially available assay based on the reverse hybridization principle. The HCV genotype-specific incidence was estimated using a previously described back calculation method. HCV genotype 1 was the most prevalent (46.9%) followed by genotype 3 (28.1%), 4 (13.2%), 2 (6.9%) and 5 (0.4%). A high prevalence of genotype 1 (66.3%) in haemophilia patients was recorded whereas HCV genotype 3 was found mainly among patients infected by I.V. drug use (58.2%). Data on the temporal patterns of HCV genotype-specific incidence in Greece revealed a moderate increase (1.3-1.6 times) for genotypes 1 and 4, and a decrease (1.5 times) for genotype 2 from 1970 to 1990, whereas there was a sharp (13-fold) increase for genotype 3. The molecular characterization of 41 genotype 4 HCV isolates belonging to various risk groups revealed that, subtype 4a was the most frequently detected (78%). Phylogenetic comparison of the Greek 4a isolates with all HCV-4a isolates reported worldwide so far revealed a topology which does not discriminate Greek isolates from the others. HCV-4 does not represent a recent introduction in Greece.
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Hepacivirus/genética , Hepatitis C/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Niño , Análisis por Conglomerados , Femenino , Genotipo , Grecia/epidemiología , Hepacivirus/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , ARN Viral/química , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genéticaRESUMEN
SUMMARY: The epidemic of hepatitis C virus (HCV) infection is a major public health issue. We conducted a comprehensive analysis to estimate future HCV-related morbidity and mortality, using a model which is the first to take into account currently available treatments. We reconstructed the incident infections per year in the past that progressed to chronic hepatitis C (CHC) in Greece. Then, the natural history of the disease was simulated in subcohorts of newly infected subjects in the presence or absence of treatment using yearly estimates of the number of treated patients obtained from national databases. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, hepatocellular carcinoma (HCC) and mortality were obtained up to 2030. The current proportion of naïve CHC patients receiving treatment in Greece is 1.2% per year. Treatment of 1.2-10% of naïve CHC patients per year would reduce the cumulative number of incident cirrhosis and HCC cases from 2002 to 2030 by 10.8-39.4% and 12.8-39.8%, respectively and decrease the number of prevalent cirrhosis and HCC cases in 2030 by approximately 17-48% compared with the number estimated under the assumption of no treatment. Approximately 17 cirrhosis cases or six HCC cases or 10 premature deaths would be prevented for every 100 treated patients. However, the prevalent cirrhotic/HCC cases because of HCV and HCV-related deaths would not plateau until 2030. Despite the introduction of effective treatment, HCV-related morbidity and mortality will likely increase during the next 20-30 years in Greece. Intensive primary prevention efforts coupled with increased access to the currently available treatments are necessary to control the chronic consequences of HCV epidemic.
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Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Predicción , Grecia/epidemiología , Hepatitis C Crónica/transmisión , Humanos , Incidencia , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , Fallo Hepático/epidemiología , Fallo Hepático/etiología , Modelos Estadísticos , Prevalencia , ProbabilidadRESUMEN
In this study, a comprehensive methodology for modelling the hepatitis C virus (HCV) epidemic is proposed to predict the future disease burden and assess whether the recent decline in the incidence of HCV may affect the future occurrence of cirrhosis and hepatocellular carcinoma (HCC) cases. Using the prevalence of HCV, the distribution of chronic hepatitis C (CHC) patients within the various transmission groups and their infection-onset times, it was possible to reconstruct the incident infections per year in the past that progressed to CHC in Greece. The natural history of the disease was simulated in subcohorts of newly infected subjects using transition probabilities derived either empirically between fibrosis stages 0-4 or from literature review. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, HCC and mortality in Greece were obtained up to 2030. HCV incidence peaked in the late 1980s at five new infections/10,000 person-years. Under the assumption of 20-100% decline in HCV incidence after 1990, the cumulative number of incident cirrhosis and HCC cases from 2002-2030 was projected to be lower by 9.6-48.2% and 5.9-29.5%, respectively, than that estimated under the assumption of no decline. However, the prevalent cirrhotic/HCC cases and HCV-related deaths are predicted to decline in the next 30 years only under the assumption of complete elimination of new HCV infections after 1990. Despite the progress in the reduction of HCV transmission, primary prevention does not seem adequate to reverse the rise in the incidence of cirrhosis and HCC.
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Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Cirrosis Hepática/epidemiología , Modelos Estadísticos , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Predicción , Grecia/epidemiología , Hepatitis C Crónica/transmisión , Humanos , Incidencia , Cirrosis Hepática/virología , Fallo Hepático/epidemiología , Fallo Hepático/etiología , Prevalencia , ProbabilidadRESUMEN
A randomized trial was conducted to assess the efficacy of interferon-alpha (IFN) daily in combination with ribavirin in 301 naïve patients with chronic hepatitis C (CHC). Patients were randomized to receive ribavirin 1.2 g daily (QD) for 48 weeks with either IFN 5 MU (thrice weekly) TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks (IFN TIW, n = 154) or IFN 5 MU QD for 8 weeks followed by IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks (IFN QD, n = 147). Treatment discontinuation rates, because of adverse events, were similar in the two arms (14.9% in IFN TIW and 14.3% in IFN QD, P = 0.87). The proportion of patients with sustained virological response (SVR) was 27.9% for patients treated TIW and 38.8% for those treated QD (P = 0.046). According to logistic regression analysis, patients in the IFN QD arm had 1.7 times higher probability of achieving SVR, than those receiving IFN TIW (P = 0.038). Low baseline viral load (P = 0.017) and genotype non-1 (P = 0.036) were associated with higher SVR rates. Combination of IFN/ribavirin for 48 weeks is more effective when IFN is administered daily for the first 24 weeks in naïve patients with CHC.
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Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Antivirales/administración & dosificación , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Ribavirina/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Antivirales/administración & dosificación , Quimioterapia Combinada , Femenino , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes , Ribavirina/administración & dosificación , Resultado del TratamientoRESUMEN
HBV DNA quantitation is used extensively for the monitoring of treatment of hepatitis B virus (HBV) infection. The aim of this study was to develop a highly sensitive and reproducible real-time PCR (RTD-PCR) assay for the quantitation of HBV DNA using the LightCycler system. The performance of this assay was assessed by analyzing serial dilutions of HBV genomic DNA of known concentration and the lower limit of detection was found to be 1 DNA copy/reaction. By using serial dilutions of plasmid standard, RTD-PCR was determined to quantify HBV DNA in a 10-log10 dynamic range. RTD-PCR was found to be more sensitive than the commercially available tests such as the Quantiplex HBV DNA and the AMPLICOR HBV MONITOR assays. The median coefficient of variation of interexperimental variability was 3.2%. The HBV DNA values obtained with RTD-PCR were highly correlated with assays available commercially. These findings suggest that our RTD-PCR assay combines high sensitivity and reproducibility for HBV DNA quantitation in an incomparable high dynamic range of quantitation.
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Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/virología , Reacción en Cadena de la Polimerasa/métodos , ADN Viral/análisis , Virus de la Hepatitis B/genética , Humanos , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Eritema/complicaciones , Hepatitis C Crónica/complicaciones , Trastornos de la Pigmentación/complicaciones , Antivirales/uso terapéutico , Eritema/patología , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/enzimología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Persona de Mediana Edad , Trastornos de la Pigmentación/patología , Proteínas Recombinantes , Ribavirina/uso terapéuticoRESUMEN
The prevalence of TT virus (TTV) infection in various population groups from Athens, Greece, was assessed by the polymerase chain reaction (PCR) using two primer sets from distinct regions of the genome: the conventional set derived from the open reading frame-1 (ORF-1) and the new, highly sensitive set targeting the region that includes the TATA signal localized upstream of ORF-2. Based on both primer sets, TTV DNA was detected in 42/50 (84.0%) healthy individuals, 42/50 (84.0%) chronic hepatitis C patients, 31/39 (79.5%) acute non-A-E hepatitis patients (group I), 14/16 (87.5%) renal failure patients with acute non-A-E hepatitis (group II), 47/50 (94.0%) intravenous drug users (IVDU), 36/50 (72.0%) hemophiliacs, and 21/31 (67.7%) hemodialysis patients. The presence of TTV was not associated with any particular risk group, and no differences were observed in relation to demographic, biochemical and virological characteristics between TTV DNA-positive and -negative patients. TTV did not seem to have a profound effect on the course of chronic C or acute non-A-E hepatitis either. Phylogenetic analysis revealed that TTV strains circulating in the greater metropolitan area of Athens belong not only to the G1 and G2 genotypes that are encountered worldwide, but also to G3 and to G5 that are found mainly in Europe and Asia, respectively. Further studies will shed light on the role of this highly prevalent virus.
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Infecciones por Virus ADN/epidemiología , Torque teno virus/genética , Adolescente , Adulto , Anciano , Cartilla de ADN , ADN Viral/genética , Femenino , Genotipo , Grecia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , Reacción en Cadena de la Polimerasa , Torque teno virus/clasificaciónRESUMEN
Only a minority of patients with hepatocellular carcinoma (HCC) may benefit from curative treatments, whereas there is no standard therapy for the remaining patients. The objective of this multicentre, open label phase II study was to estimate the objective tumour response rate of a 28-day regimen of oral eniluracil/5-fluorouracil (5-FU) in patients with chemotherapy-naïve, or anthracycline-refractory, inoperable HCC. 45 patients received courses of twice daily oral 5-FU (1.0 mg/m(2)) and eniluracil (10 mg/m(2)) for the first 28 days of each 5-week course. Patients were assessed at regular intervals to determine the tumour response and to evaluate toxicity. Patients were followed-up for a minimum of 6 months. No patient showed a partial or complete tumour response, and 18 patients (40%) had a best response of stable disease (95% confidence interval (CI) 25%, 55%). The median duration of progression-free survival (PFS) was 13.7 weeks (95% CI 10.0-20.0 weeks), and the median duration of overall survival (OS) was 50.3 weeks (range 1.1-64.1+ weeks). The combination of eniluracil/5-FU was well tolerated and had an acceptable safety profile. Only 7 patients (16%) reported at least one adverse event (AE) of grade 3 or 4 intensity considered reasonably attributable to the study medication. In conclusion, oral eniluracil/5-FU had minimal, if any, activity in patients with inoperable HCC, but the safety profile was acceptable.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Uracilo/administración & dosificación , Uracilo/efectos adversos , Uracilo/análogos & derivadosRESUMEN
The relevance of GB virus C/hepatitis G virus (GBV-C/HGV) infections in liver pathology remains unclear. To investigate the epidemiology of GBV-C/HGV in Athens, Greece, sera from 512 subjects were screened for present and past markers of GBV-C/HGV infection using a reverse transcription-polymerase chain reaction (RT-PCR) and a serological assay, respectively. GBV-C/HGV RNA was detected in 18/56 (32.1%), 12/42 (28.6%), and 16/55 (29.1%) patients with acute hepatitis B, C, or non-A-E, and in 5/58 (8.6%) and 18/68 (26.5%) patients with chronic hepatitis B or C, respectively, as well as in 50/133 (37.6%) hemodialysis patients and 10/100 (10%) healthy individuals. The data indicated that GBV-C/HGV seroprevalence is age-dependent; thus, GBV-C/HGV RNA and anti-E2 positivity were shown to be associated with younger age [odds ratio 0.98, 95% confidence interval (CI) 0. 97-1.00, P = 0.017] and older age (odds ratio 1.03, 95% CI 1.01-1.05, P = 0.002), respectively. No significant associations were identified between GBV-C/HGV RNA status and alanine aminotransferase (ALT) levels in either hepatitis or hemodialysis patients. Nevertheless, GBV-C/HGV RNA-positive acute non-A-E hepatitis patients were more likely to manifest a more severe clinical form of acute hepatitis (P = 0.024). Phylogenetic analysis of partial 5'-untranslated region sequences isolated from 18 viremic individuals showed that most GBV-C/HGV strains circulating in the greater metropolitan area of Athens belong to the 2a subgroup. A genetically diverse type 2 sequence that may represent a novel subtype within group 2 was also characterized.
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Flaviviridae/genética , Hepatitis Viral Humana/epidemiología , Epidemiología Molecular , Regiones no Traducidas 5'/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Femenino , Flaviviridae/inmunología , Flaviviridae/aislamiento & purificación , Grecia/epidemiología , Anticuerpos Antihepatitis/sangre , Hepatitis Viral Humana/virología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , ARN Viral/sangre , Análisis de Secuencia de ADN , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P <.001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (>/=2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B.
Asunto(s)
ADN Viral/análisis , Antígenos e de la Hepatitis B/análisis , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Antígenos del Núcleo de la Hepatitis B/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Precursores de Proteínas/genética , Resultado del TratamientoRESUMEN
Hepatitis E infection is associated with areas in which hepatitis E virus (HEV) infection is endemic. Acute infections in industrialized nations are usually linked to travel to endemic areas. Recently, an acute hepatitis infection in a patient from the United States (US), with no recent foreign travel history, was linked to a novel strain of HEV. Although a few additional cases have been reported from patients who have not traveled to endemic areas, the source of these infections has not been determined. The objective of this study was to identify additional HEV isolates from patients with acute infection who had no recent history of travel to areas where HEV is considered endemic, and to determine the genetic relationship between these and other HEV isolates. Viral RNA was isolated from serum and polymerase chain reaction (PCR) was performed using consensus primers based on a number of HEV isolates. HEV sequence in open reading frame (ORF) 1 and ORF2 was identified in three patients from nonendemic areas, one from Italy and two from Greece. Comparative and phylogenetic analyses were performed. The Greek and Italian isolates were significantly divergent from two isolates from the US and isolates identified previously from HEV-endemic regions. The Italian isolate was distinct from the two Greek isolates. In addition, the two Greek isolates were significantly divergent from each other. Phylogenetic analysis indicated that the Italian and two Greek isolates represent three new genotypes of HEV, distinct from the Burmese, Mexican, and US genotypes.
Asunto(s)
Virus de la Hepatitis E/clasificación , Virus de la Hepatitis E/genética , Hepatitis E/virología , Asia , Secuencia de Bases , ADN Viral , Europa (Continente)/epidemiología , Genotipo , Hepatitis E/epidemiología , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADNRESUMEN
A certain group of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels, despite the replication of hepatitis C virus (HCV) in infected liver cells and detection of HCV RNA in serum. These patients are usually asymptomatic and are discovered fortuitously, generally after a volunteer blood donation. A standard definition for this group of patients is obviously needed, which should include the presence of anti-HCV, detectable serum HCV RNA by polymerase chain reaction and persistently normal ALT levels. These patients have minimal or mild necroinflammatory lesions in liver tissue specimens and cirrhosis is rare. The natural course of the disease in this epidemiologic setting is unknown, but the progression is probably good. Alpha-interferon has been administered in small pilot studies and three controlled studies. Overall, the end of treatment response was 35% and the sustained virologic response 15%. These response rates are similar to those reported in patients with elevated ALT levels. More important, serum ALT levels became abnormal during therapy in 47% of the patients and levels remained elevated in some patients after therapy. Prospective studies on the long-term natural history of HCV infection in this setting are needed and well designed randomized controlled trials are necessary to determine whether these patients would benefit from IFN or a combination treatment with ribavirin regimen. Currently, there is no rationale to treat these patients.
Asunto(s)
Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Hepacivirus/genética , Humanos , ARN Viral/sangre , Valores de ReferenciaRESUMEN
BACKGROUND/AIMS: Chronic hepatitis C appears to have a highly variable natural course with 20% of patients developing cirrhosis within 20 years, while the majority of them run a relatively mild course. We studied the relationships of epidemiological, biochemical and virological features with histological severity (grade) and liver disease progression (stage). METHODOLOGY: Liver histology, serum HCV RNA level and HCV genotype were determined in a well-defined cohort of 152 consecutive (100 males, 52 females) patients with chronic hepatitis C. RESULTS: Patients with minimal or mild chronic hepatitis were significantly younger than those with moderate or severe chronic hepatitis (mean age: 41.1 vs 49.5 years respectively, p=0.003). On the other hand, patients with no or mild fibrosis compared to those with moderate or severe fibrosis and to those with cirrhosis were significantly more frequently males (73%, 64% and 43%, p=0.01), parenteral drug users (36%, 11% and 11%, p=0.01) and infected with other than 1b genotype (86%, 52% and 33%, p<0.0001), significantly younger (mean age: 37, 48 and 58 years, p<0.0001) and had significantly lower HCV RNA levels (geometric mean: 6.9, 19.2 and 17.5 x 10(5) eq/ml, p=0.007). Multivariate analysis showed that stage was significantly related only to patient age (p<0.0001), HCV genotype (p=0.0025) and HCV RNA level (p=0.044). CONCLUSIONS: In chronic hepatitis C, histological severity seems to be associated only with patient age, while progression of the disease is mainly associated with patient age, HCV genotype and viremia level.
Asunto(s)
Hepatitis C Crónica/patología , Adulto , Progresión de la Enfermedad , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Hígado/patología , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , ARN Viral/análisisRESUMEN
An RT-PCR assay using primers from the 5'-UTR of the GBV-C/HGV genome was used to detect viremia, and a serological assay was used to detect past exposure to GBV-C/HGV, in sera from 106 imprisoned Greek intravenous drug users. High seroprevalence rates indicative of the parenteral route of transmission of the virus were found (32.1% for GBV-C RNA and 46.2% for anti-GBV-C E2). These rates were nonetheless lower in comparison to the corresponding rates of HCV infection markers (64.2% for HCV RNA and 77.4% for anti-HCV). Statistically significant univariate associations were observed between GBV-C-RNA positivity and younger age (P=0.006) and HCV-RNA positivity (P=0.024), as well as with higher serum alanine aminotransferase levels (P< 0.001); this latter association was shown to be independent of coinfection with HCV and of age by a multiple logistic regression model. Apparently, GBV-C/HGV had spread readily by needle-sharing in prison, while causing acute subclinical hepatitis in infected inmates. Phylogenetic analysis of the partial 5'-UTR of the GBV-C/HGV genome from 16 seropositive individuals, which delineated their grouping within genotype 2, also revealed a close genetic relationship between two sets of sequences from 4 drug addicts, 3 of whom admitted to sharing needles while imprisoned.