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Biomedical subjects

Josep Costa

Publications and source records attributed to Josep Costa.

10 recordsLinked to original sources

Predictive value of early virologic response in HIV/hepatitis C virus-coinfected patients treated with an interferon-based regimen plus ribavirin.

BACKGROUND: As a result of adverse events, a moderate rate of virologic response, and high costs associated with hepatitis C virus (HCV) therapy, finding early markers of sustained treatment response is a clinical priority. In the HCV-monoinfected population, a reduction >or=2 log in plasma HCV RNA at week 12 of therapy (early virologic response [EVR]) predicts a sustained virologic response (SVR). Few data are available in HIV/HCV-coinfected patients, however. METHODS: A subanalysis of data from HIV/HCV-coinfected patients treated with pegylated interferon-alpha-2b (PEG, 100-150 mug/wk) or interferon-alpha-2b (IFN, 3 MIU 3 times per week) plus ribavirin (RBV, 800-1200 mg/d) was conducted in a randomized single-center clinical trial. The duration of treatment was 48 weeks (only 24 weeks for HCV genotype 2 or 3 with a baseline HCV RNA level <800,000 IU/mL). RESULTS: Ninety-five patients were randomized (43 assigned to IFN + RBV and 52 assigned to PEG + RBV). Eighty patients completed at least 12 weeks on therapy and were included in the EVR analysis. Thirty-five (43%) of them attained an SVR (56% and 30% of patients treated with PEG and IFN, respectively; P = 0.026). An EVR occurred in 55 (69%; 80% of PEG + RBV group and 56% of IFN + RBV group). Overall, 35 of 55 patients with an EVR were sustained responders, yielding a positive predictive value of 64% (70% in PEG + RBV arm and 55% in IFN + RBV arm). None of the patients who demonstrated an HCV RNA decline of <2 logs at week 12 reached an SVR (negative predictive value of 100%). CONCLUSION: Our results confirm the utility of an EVR to predict the chance of the lack of an SVR in HIV/HCV-coinfected patients, particularly those treated with PEG.

Adult↗

HCV virological assessment.

Virological assessment of HCV infection relies on a series of assays that are essential for diagnostic purposes and to adopt therapeutic decisions. Diagnostic assays can be classified in three groups: assays that are designed to detect specific antibodies to HCV; techniques that detect and quantify viral load; and tests aimed at determining the infecting HCV type. In general, the use of these assays is similar in HCV infected patients as in those co-infected with HCV and HIV. Co-infected patients, however, have some inherent characteristics (deficient immune status, high HCV-RNA concentrations, particular genotype distribution, low response to antiviral therapy) that make the interpretation of such assays slightly different. Regarding assays to detect antibodies to HCV, last generation tests have a similar sensitivity in mono-infected and co-infected individuals. HCV-RNA testing might be helpful in anti-HCV negative individuals with clinical or analytical suspicion of liver disease. Genotype determination in patients co-infected with HCV and HIV should be performed by methods relying on sequence analysis, since serotyping assays have shown a lower sensitivity in co-infected cohorts. HCV-RNA concentration is a strong predictor of response to therapy. Due to the higher viral load of co-infected patients compared to HCV mono-infected individuals, those assays with a wide dynamic range seem more appropriate to monitor viral load during treatment.

Hepacivirus↗

Rubella elimination programme strengthened through measles elimination programme in Catalonia.

The drastic fall in rubella cases recorded in Catalonia from 1988 on, when the second dose of Measles-Mumps-Rubella (MMR) vaccine was implemented, and especially from 1998, when the measles elimination programme began, led to the introduction, in May 2002, of the rubella and congenital rubella syndrome elimination by 2005 programme. From May 2002 to May 2004, 13 suspected rubella cases were reported to the Statutory Disease Reporting System; of these, one postnatal case and one congenital rubella case were confirmed (15.4%), both being imported cases. Through the screening of viruses established in the measles elimination programme, 28 possible cases were analyzed and six (21.4%) confirmed imported postnatal rubella cases were detected. The small number and imported nature of the cases of rubella and the detection of the majority of the confirmed cases through the measles elimination programme, strongly suggests that both programmes should continue.

Adolescent↗

Performance of hepatitis C virus core antigen immunoassay in monitoring viral load after liver transplantation.

BACKGROUND: In the liver transplantation (LTx) setting, there are several situations where measurement of hepatitis C virus (HCV)-RNA concentration may provide relevant information. However, HCV-RNA quantification is expensive and not routinely available in all laboratories. An assay to quantify total HCV core antigen in serum has been recently developed. The aim of this study was to compare the performance of HCV-RNA and HCV core antigen determination in a cohort of 116 HCV-infected patients who underwent LTx. METHODS: HCV-RNA and HCV core antigen concentrations were determined in serum samples (n=435) obtained before LTx and at weeks 4, 12, and 48 after LTx. RESULTS: There was an excellent correlation between HCV-RNA and HCV core antigen levels (r=0.802 P<0.001), with an equivalence of 9,900 IU/mL of HCV-RNA per pg/mL of HCV core antigen. The determination of core antigen was linear in samples containing between 20,000 and 2,500,000 IU/mL of HCV-RNA and highly reproducible (mean coefficient of variation, 15%). Overall, HCV core antigen tested positive in 378 (92%) of 410 samples with detectable HCV-RNA (>600 IU/mL); the percentage increased to 98% in samples taken later than 4 weeks after LTx. In fact, almost all samples (369 of 375 [98.4%]) with HCV-RNA levels higher than 20,000 IU/mL were positive for HCV core antigen, whereas 56 of 57 samples with undetectable core antigen had HCV-RNA levels below 50,000 IU/mL. CONCLUSIONS: The performance of total HCV core antigen immunoassay is appropriate for monitoring viral load in HCV-infected patients undergoing LTx and might be considered a useful alternative to HCV-RNA testing.

Cohort Studies↗

Prevalence of hepatitis A antibodies in schoolchildren in Catalonia (Spain) after the introduction of universal hepatitis A immunization.

The objective of this study was to investigate the prevalence of hepatitis A antibodies (anti-HAV) in schoolchildren in Catalonia and to compare it with the rates found in previous studies. Sera from a representative sample of 1,342 children aged between 6 and 15 years, recruited in 2001, were tested for anti-HAV. The results were related to sociodemographic variables and vaccination history. The overall prevalence of anti-HAV was 51.4%. The prevalence was 5.5% in non-vaccinated children, similar to that found in a 1996 study, and 96.6% in vaccinated children. The prevalence of anti-HAV in non-vaccinated children increased significantly with age, reaching 11.6% in the 13-15 years age group. The prevalence of anti-HAV was higher in children born outside Catalonia than in those born in Catalonia (16.1% vs. 5.0%, P = 0.02). The expected continuation in the decline in the prevalence of anti-HAV in non-vaccinated schoolchildren, observed in Catalonia since 1986, was not found in 2001. The rate of anti-HAV in 2001 was slightly higher than in 1996, although the difference was not statistically significant (5.5 and 3.5%, respectively). This could be explained by the increased number of recent immigrant children born outside Catalonia, mainly in countries where hepatitis A is highly endemic.

Adolescent↗

[Real-time PCR].

PCR based assays are currently used routinely in most microbiology laboratories. But, with few exceptions, they are restricted to the field of virology, especially to a limited number of viral targets with important economical interest for which commercially well standardized assays are available. For several reasons, it has had a poor implementation of the PCR assays into routine diagnostics for other infectious diseases despite they are advantageous. Combined with automated sample isolation of nucleic acids, real-time PCR gives an ideal platform for the development of molecular assays for a wide range of infectious agents with clinical interest. Because of its advantages, as simplicity, rapidity and minor risk of contamination, real-time PCR will go replace conventional PCR assays and its use will extend to a wide range of applications in clinical microbiology.

Bacterial Typing Techniques↗

Treatment of patients with progressive unresectable metastatic melanoma with a heterologous polyvalent melanoma whole cell vaccine.

Unresectable metastatic melanoma has no elective treatment. Neither chemotherapy, intravenous IL-2 nor biochemotherapy clearly improves the overall survival. Recent assays with therapeutic vaccines have been recently yielded promising results. Here, we describe the application, clinical tolerance and antitumoural activity of a heterologous polyvalent melanoma whole cell vaccine in patients with metastatic melanoma. Twenty-eight AJCC stage III/IV melanoma patients with progressive unresectable metastatic disease were treated with our heterologous polyvalent melanoma whole cell vaccine between July 1, 1998 and July 1, 2002. All patients had already been unsuccessfully treated with high doses of IFN-alpha2 and/or polychemotherapy and/or biochemotherapy and/or perfusion of extremities, or could not receive other treatments due to their age or underlying illness. Twenty-three were assessable. The vaccine was constituted by 10 melanoma cell lines, derived from primary, lymph node and metastatic melanomas. Prior to intradermal inoculation, the cells were irradiated and mixed with BCG, and 50% were treated with DNFB. After a median follow-up of 19 months, 26% of patients responded: 3 CR (18, 16+, and 26+ months), 2 PR (8 and 22 months) and 1 MR (36+ months). The median survival of the whole group was 20.2 months. None of the 28 patients initially included in the study presented significant toxicity. This vaccination program had specific antitumoural activity in advanced metastatic melanoma patients and was well tolerated. The clinical responses and the median survival of our group of patients, together with the low toxicity of our polyvalent vaccine, suggest that this approach could be applied to earlier metastatic melanoma patients.

Adult↗

Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients.

BACKGROUND & AIMS: The aim of this study was to investigate if the variable outcome of chronic hepatitis B may be related to hepatitis B virus (HBV) genotype. METHODS: The clinical and virologic events observed over prolonged follow-up in 258 Spanish patients with chronic hepatitis B infected with different genotypes of HBV were compared. RESULTS: The prevalence of genotype A, D, and F was 52%, 35%, and 7%, respectively. Concomitant sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A- than in genotype D- (log-rank, 14.2; P = 0.002) or genotype F-infected patients (log-rank, 4.2; P = 0.03). The rate of hepatitis B surface antigen (HBsAg) clearance was higher in genotype A than in genotype D hepatitis (log-rank, 4.6; P = 0.03). Sustained remission and clearance of HBsAg were associated with infection with genotype A by Cox regression analysis. Seroconversion to antibody to hepatitis B e antigen (anti-HBe) was unrelated to HBV genotype, but the rate of sustained remission after seroconversion was higher in genotype A than in genotype D hepatitis both in patients who seroconverted to anti-HBe during follow-up (log-rank, 4.5; P = 0.03) and in patients with positive anti-HBe at baseline (log-rank, 6.66; P = 0.009). Death related to liver disease was more frequent in genotype F than in genotype A (P = 0.02) or genotype D (P = 0.002) hepatitis. CONCLUSIONS: The long-term outcome of chronic hepatitis B is different in patients infected with HBV genotype A, D, or F.

Adult↗

Hepatitis C virus kinetics during and immediately after liver transplantation.

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.

Adult↗