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Analysis of associations of HLA and HPA polymorphisms, indicators of autoimmunity and rheumatic manifestations in hepatitis C

Grant number: 11/22049-6
Support type:Regular Research Grants
Duration: July 01, 2012 - December 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Giovanni Faria Silva
Grantee:Giovanni Faria Silva
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers: Natália Bronzatto Medolago

Abstract

Hepatitis C has been associated with various extrahepatic manifestations such as joint involvement. In 90 HCV positive patients, rheumatic manifestations were found in 31%. Arthralgia is the most common, however the arthritis appears in 4% of the cases as a symmetric polyarthritis similar to rheumatoid arthritis (RA) or a mono-oligoarthritis intermittent. Clinically, HCV related to arthritis may be indistinguishable from RA, since the majority of patients fulfilling the criteria of the American College of Rheumatology for the diagnosis of RA, making it difficult to distinguish one from the other. The rheumatoid factor (RF) and crioglobulines may be present in about 40 to 70% of patients with chronic HCV, which does not help in the differential diagnosis. The cyclic citrullinated peptide antibodies (anti-CCP) are considered good markers for RA, due to their high specificity and sensitivity, they can be useful in distinguishing between HCV arthritis and RA. In addition to these immunological changes cited, the genetic factors of the hosts contribute to the development of both rheumatoid arthritis such as that one related to Virus C. One factor has been linked to bleaching or persistence of the virus, progression of liver fibrosis, therapeutic response and extrahepatic manifestations. Similarly, a polymorphism of human platelet antigens (HPA), which had been associated with certain disease, have recently been associated with hepatitis C, but without considering other events associated with infection as the presence of rheumatic manifestations. The evaluation of these genetic polymorphisms may reflect greater susceptibility to arthritis and be indicative of a more severe disease. This study is of great importance, therefore lacking in the literature that establish correlations between rheumatologic manifestations of HCV, HLA and HPA. Objective: This essay has the objective to evaluate possible associations of autoimmunity indicators of HLA and HPA polymorphisms with clinical disease. Materials and methods: This study will be a cross-sectional study with 160 patients with Chronic Hepatitis C, which will be evaluated in the personal history, clinical evaluation in consultation with the patient and survey of medical chart, collection and storage of blood samples for HLA / HPA, survey of rheumatoid factor and Anti-CCP. The sample size was determined by Fisher and Belle formula, using a confidence interval of 95%, accuracy of 7% and a ratio of 31% infected with hepatitis C who have rheumatic manifestations. Categorical variables will be analyzed through tables of absolute and relative frequencies. For continuous variables it will use descriptive statistics. Values are presented as average (standard deviation) or median (including the top quartile and bottom quartile). Associations between serologic indicators of autoimmune and rheumatologic manifestations, and between HLA and HPA polymorphism and rheumatic manifestations will be analyzed. The significance level adopted is 5%. If associations with hepatitis C virus infection were confirmed, will be possible to have prognostic connotations of rheumatologic manifestations in the course of hepatitis C, providing a more suitable therapeutic study of the subject. (AU)

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