Browsing by Author "Velosa, J"
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- Chronic hepatitis C treated with peginterferon alfa plus ribavirin in clinical practicePublication . Velosa, J; Serejo, F; Bana, T; Redondo, I; Simão, A; Vale, A; Pires, S; Macedo, G; Marinho, R; Peixe, P; Sarmento, J; Matos, L; Calinas, F; Carvalho, A; Figueiredo, ABACKGROUND/AIMS: The role of genotype and viremia were retrospectively evaluated on sustained virological response (SVR) rates in routine clinical practice. METHODOLOGY: From 1907 patients with chronic hepatitis C proposed for treatment, we analysed 1380 (1124 naive and 256 treatment-experienced) with complete follow-up. Genotype and HCV RNA quantification were assayed by commercial tests. Viremia was considered high if >800,000IU/mL, and low if <400,000IU/mL. Liver fibrosis was staged in 614 patients. RESULTS: Genotype 1 was the most frequent (60%), followed by 3 (25%), 4 (9%) and 2 (2%); 3.2% had other or unclassified genotype. Genotype 1 was more prevalent in central Portugal and genotype 4 in the south. Viremia was =800,000IU/mL in 54.6% and <400,000IU/mL in 34.6% of the patients, particularly in genotype 2 (p<0.03) and 4 (p<0.001). Genotype non-1 had a significantly lower viral load (p=0.004). Mild or moderate fibrosis was present in 71.7% and bridging fibrosis or cirrhosis in 28.3%, with no differences among genotypes. Treatment was discontinued in 19.8%. SVR was achieved in 55.3% of naive and 36.3% of re-treated patients. CONCLUSIONS: Standard treatment of chronic hepatitis C in real-life achieves similar results obtained in clinical trials, despite differences of demographic and viral parameters.
- Clinical and genetic factors predicting response to therapy in patients with Crohn's diseasePublication . Cravo, M; Ferreira, P; Sousa, P; Moura-Santos, P; Velho, S; Tavares, L; Deus, JR; Ministro, P; Silva, J; Correia, L; Velosa, J; Maio, R; Brito, MAIM:To identify clinical and/or genetic predictors of response to several therapies in Crohn's disease (CD) patients. METHODS:We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. RESULTS:Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005). CONCLUSIONS:In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.
- IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.Publication . Cravo, M; Ferreira, P; Sousa, P; Moura-Santos, P; Velho, S; Tavares, L; Deus, JR; Ministro, P; Peixe, P; Correia, L; Velosa, J; Maio, R; Brito, MOBJECTIVE: We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. PATIENTS AND METHODS: A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. RESULTS: Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03). CONCLUSION: Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.
- One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.Publication . Areias, J; Calinas, F; Porto, A; Carvalho, A; Freitas, D; Macedo, G; Noronha, R; Cotter, J; Meliço-Silvestre, A; Peixe, R; Pratas, J; Barrote, D; Teixeira, R; Augusto, F; Carrilho, I; Campante, F; Velosa, J; Carvalho, L; Duarte, M; Guerreiro, H; Pires, C; Silva, A; Cotrim, I; Guedes, F; Tomé, L; Marcelino, M; Gonçalves, C; Ferreira, E; Matos, L; Peixe, P; Esteves, J; Valente, T; Simões, C; Marinho, C; Jasmins, L; Vieira, M; Marinho, R; Matos, P; Estevans, J; Carrasquinho, J; Salsedo, G; Parada, P; Teixeira, COBJECTIVE: To further verify the efficacy and safety of locally manufactured lamivudine on patients with chronic hepatitis B (CHB). METHODS: 2200 patients with CHB were recruited and received lamivudine orally 100 mg once daily for 12 months. The efficacy assessments included virologic response rate (defined by the absence of serum HBV DNA, HBeAg loss and HBeAg/HBeAb seroconversion), percentage of patients with normalization of alanine aminotransferase (ALT). Meanwhile improvement of quality of life (QOL) measured by mos SF-36 QOL questionnaire and liver histology evaluation were conducted in some patients. The safety assessments included adverse events, serious adverse events and laboratory abnormalities. All 2200 patients received at least one dose of medication and were all included in the safety population. RESULTS: Ninety seven percent of patients (2137/2200) recruited were HBV DNA positive by dot blot (sensitivity GRT or equal to 1.0 pg/ml) at baseline. At the end of 12 months treatment, HBV DNA was undetectable in 80% patients (1538/1920) with HBV DNA positive before treatment. Among the 79%(1744/2200) of the patients recruited had positive HBV DNA accompanied abnormal ALT levels at baseline, 72% patients became ALT normal. And among the 84% (1843/2200) of the patients recruited were HBV DNA and HBeAg positive, anti-HBe negative, 16% (269/1650) patients achieved HBeAg/HBeAb seroconversion after 12 months of lamivudine treatment. The HBeAg/HBeAb seroconversion rate was positive correlation to the ALT level before treatment. A total of 304 patients completed the health-related QOL questionnaire. After 12 months treatment, lamivudine improved both their physical and mental health, especially for their mental health. 133 evaluable, paired liver biopsies were obtained for histological assessment, among whom 115 patients had abnormal ALT levels at baseline. Compared with pre-treatment most of their liver injury got alleviated (51.9%) or no further deterioration (36%), only 12% worsening. During the 12 months treatment, 9% patients withdrew from the study and 17% patients showed at least one adverse event, mild or moderate. There were no obvious difference between this study and the previously reported lamivudine Phase II or III study with regard to the kinds, incidence and severity of adverse events. CONCLUSION: The efficacy and safety profile of the locally manufactured lamivudine 100 mg tablets are similar with those of the previously reported available lamivudine tablets imported in treating Chinese chronic hepatitis B patients.