The TNF-α -308 polymorphism may affect the severity of Crohn's disease

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease

Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C

Background: Major depression is a frequent adverse effect of interferon-alpha (IFN-alpha) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-alpha-induced depression, no pharmacogenetic study has investigated Whether variation in the IDO gene modifies vulnerability to this adverse effect.Methods: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-alpha plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072).Results: MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-alpha therapy. No association with the diagnosis of a major depressive episode during the course of IFN-alpha therapy was observed genotype or allele-wise (p > 0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-alpha-related depression (p 0.05).Conclusions: Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-alpha-related depression in the Brazilian population. Interferon-alpha-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. the cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-alpha-induced depression. (C) 2011 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Bahia, Sch Med, Dept Neurosci & Mental Hlth, BR-41170290 Salvador, BA, BrazilUniv Fed Bahia, Univ Hosp, Psychiat Serv, BR-41170290 Salvador, BA, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Inst Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychobiol, São Paulo, BrazilUniv Fed Bahia, Sch Med, Dept Gastroenterol, BR-41170290 Salvador, BA, BrazilUniversidade Federal de São Paulo, Sch Med, Hepatitis Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hosp São Paulo, São Paulo, BrazilHarvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, Sch Med, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Inst Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hepatitis Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hosp São Paulo, São Paulo, BrazilCNPq: 471592/2008-0CNPq: 142262/2008-0Web of Scienc

Daily interferon induction regimen using different manufactured interferons (alpha-2a or alpha-2b) in combination with ribavirin for treatment of chronic hepatitis C: a prospective randomized study Esquema de indução diário com interferon alfa 2-a ou alfa 2-b em combinação com ribavirina para tratamento da hepatite crônica C: estudo prospectivo randomizado

BACKGROUD: Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. AIMS: To evaluate the safety and efficacy of interferon alpha daily induction regimen in combination with ribavirin. PATIENTS AND METHODS: A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response RESULTS: Eighty three patients completed treatment, five dropped out (one from IFN TIW and four from IFN QD) and in five patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically significant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29%, similar in both groups. In the "intention to treat" analysis the overall sustained virological response was 39.8%. There was no significant difference in sustained virological response rate between both treatment strategies (36.4% IFN TIW vs 42.9% IFN QD). In the 83 patients who finished the trial, sustained virological response was 44.6%. Among subjects with HCV genotype-1, the sustained virological response was 42% (40.9% IFN TIW vs 42.9% IFN QD) and among patients with HCV genotype 2 or 3, the sustained virological response was 55.6% (50% IFN TIW vs 63.6% IFN QD) CONCLUSIONS: Combination therapy had an overall sustained virological response rate of 39.8% ("intention to treat analysis"). There was no difference with respect to sustained virological response rates between patients who used daily induction schedule compared to standard regimen. Adverse events, even more frequent in the daily induction group, did not interfere with the treatment strategies.<br>RACIONAL: Estudos em cinética viral na hepatite C demonstraram que há uma queda dos níveis séricos de interferon 48 h após a sua administração, quando a carga viral do vírus C volta a se elevar. Antes da disponibilidade do interferon peguilado, diversos ensaios clínicos investigaram a terapia de indução com interferon standard OBJETIVOS: Avaliar a segurança e eficácia do esquema de indução diário com interferon alfa associado à ribavirina. PACIENTES E MÉTODOS: Noventa e três pacientes com hepatite crônica C foram incluídos. Através de randomização, foram alocados em um de dois braços terapêuticos: 44 indivíduos no grupo A: IFN 3MU três vezes por semana + ribavirina 1,0-1,2 g diariamente por 48 semanas e 49 indivíduos no grupo B: IFN 3MU diariamente por 12 semanas, seguindo-se por IFN 3MU três vezes por semana até completar 48 semanas + ribavirina 1,0-1,2 g diariamente por 48 semanas. A genotipagem do vírus C foi realizada em 85 indivíduos. Considerou-se resposta virológica sustentada a persistência do HCV-RNA negativo 6 meses após o término da terapia RESULTADOS: Oitenta e três pacientes completaram o tratamento. Houve cinco abandonos (um do grupo A e quatro do grupo B) e em cinco pacientes a terapia foi retirada devido a efeitos adversos (dois do grupo A e três do grupo B). Não houve diferença estatisticamente significante entre os grupos quanto à interrupção do tratamento. A freqüência de cirrose foi 29%, semelhante entre os grupos. Na análise "intention to treat" a resposta virológica sustentada foi 39,8%. Não houve diferença estatística na taxa de resposta virológica sustentada entre ambas as estratégias terapêuticas (36,4% grupo A vs 42,9% grupo B). Nos 83 pacientes que finalizaram o estudo, a resposta virológica sustentada foi 44,6%. Entre os pacientes com genótipo 1, a resposta virológica sustentada foi 42% (40,9% grupo A vs 42,9% grupo B) e entre os pacientes com genótipo 2/3, a resposta virológica sustentada foi 55,6% (50% grupo A vs 63,6% grupo B) CONCLUSÕES: A taxa de resposta virológica sustentada foi 39,8% para a terapia combinada (análise "intention to treat"). Não houve diferença entre as taxas de RVS do grupo de indução comparado ao regime padrão. Efeitos adversos, mesmo mais freqüentes no grupo de indução, não interferiram nas estratégias terapêuticas

Thalidomide induces mucosal healing in Crohn's disease: Case report

Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract that is defined by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn’s disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn’s disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximab after three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response