MTTP polymorphisms and hepatic steatosis in individuals chronically infected with hepatitis C virus.

Polymorphisms in the microsomal triglyceride transfer protein (MTTP) gene were genotyped in individuals who were chronically infected with hepatitis C virus (HCV). In the 236 patients, the frequencies of risk alleles of the -164T/C (rs1800804), -400A/T (rs1800803) and H297Q (rs2306985) polymorphisms were 0.30, 0.41 and 0.50, respectively. A significant association between the risk alleles of the -164T/C and -400A/T polymorphisms combined with HCV genotype 3 infection and the occurrence of steatosis was detected (p = 0.004 and p = 0.032), suggesting that a combination of host and viral factors can potentially be used to predict hepatic steatosis.

Genetic variation in the microsomal triglyceride transfer protein (-493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus.

BACKGROUND: In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV). METHODS: Two hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G/T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses. RESULTS: The most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G/T SNP in patients infected with HCV genotype 3 (P < 0.001). CONCLUSIONS: In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C.

BACKGROUND: Prospective studies have shown that 80% of acute hepatitis C virus (HCV) cases progress to chronic infection; approximately 10-20% of patients with these conditions will develop liver cirrhosis within 2 to 3 decades, and 1-5% will develop liver cancer. Some studies have indicated that the rs738409 polymorphism of the PNPLA3 gene is associated with steatosis and the progression of advanced fibrosis. This study assessed the contribution of the PNPLA3 rs738409 polymorphism with regard to the steatosis and degree of liver fibrosis in Brazilian patients diagnosed with chronic hepatitis C. METHODS: A total of 290 patients were evaluated at the Clinics Hospital of the School of Medicine, University of São Paulo, between 2010 and 2015. The inclusion criteria were age ≥ 18 years and positive anti-HCV antibody and HCV RNA tests. The participants were evaluated based on medical consultation, blood tests, and liver biopsies conducted before specific antiviral therapies were applied. The associations between the rs738409 PNPLA3 gene polymorphism and steatosis and advanced fibrosis were tested under a recessive inheritance model using logistic regression analysis, including age, gender, BMI, ethnicity/color, HOMA-IR, alcohol intake, HCV genotype 3, and the rs58542926 TM6SF2 gene polymorphism as covariates. RESULTS: The mean age of the patients was 54.9 years old (range, 28 to 82 years), and 124 (42.8%) patients were male; 226 (77.9%) were white, 43 (14.8%) were pardo, and 21 (7.2%) were black Brazilians. Of the patients included in this study, 133 (45.9%) presented with the CC genotype, 63 (21.7%) with the CG genotype, and 94 (32.4%) with the GG genotype of the PNPLA3 gene I148M variant. We observed that the associations between PNPLA3 rs738409 GG genotype and steatosis was significant (OR: 2.16; 95% CI 1.26-3.72). The same genotype was associated to advanced fibrosis too (OR:2.64; 95% CI 1.26-5.53). CONCLUSIONS: Associations between the rs738409 polymorphism of the PNPLA3 gene genotype GG and hepatic steatosis and advanced fibrosis were observed. Studies are still needed to clarify the influence of these polymorphisms on hepatic steatosis and degree of fibrosis among individuals diagnosed with chronic hepatitis C.

Informaçöes sobre aids: subtipos do HIV-1 / Informations about aids: subtypes of HIV-1

No Brasil, pelo menos três subtipos foram encontrados até o momento: B, C e F. Isso sugere que, possivelmente, a epidemia aqui teve mais de uma porta de entrada. O percentual de divergência entre amostras de 1992, oriundas do Brasil, tidas como do subtipo B, correspondeu a 14,1 por cento. Isso leva a acreditar que o princípio da epidemia deu-se no final da década de 70 e primórdios dos anos 80

Patogênesi da AIDS: possível papel dos co-fatores na reativaçäo do HIV / Pathogenesis of AIDS: possible role of the co-factors on HIV reactivation

Um dos aspectos mais intrigantes da patogênese da AIDS é o da longa permanência do HIV em células humanas sem causas lhes efeito citopático durante vários anos, em alguns portadores assintomáticos, e causando destruiçäo celular, e doença, a curto prazo, em outros. Foram descritos vários agentes e os mecanismos por eles utilizados para reativar o HIV latente, "in vitro" e "in vivo" (culturas de tecidos), assim como a observaçäo epidemiológica da frequente presença de tais agentes no individuo com AIDS doença, reforçando a hipótese de atuarem os mesmos como reativadores do provírus latente. Foram feitas, nesse contexto, consideraçöes especiais para os vírus da hepatite B, herpesvírus HHV-1, 2 e 6, citomegalovírus, vírus EB, retrovírus HTLV-1 e 2, arbovírus do grupo B (vírus Maguary), malária e outras doenças endêmicas que acometem milhöes de brasileiros. Reconhecendo-se a importância da atuaçäo de tais fatores sobre os gens reguladores da expressäo viral na prevençäo indireta da eclosäo da AIDS-doença

Presença do HIV-1 e HIV-2 no Brasil: perspectivas epidemiológicas / The presence of HIV-1 and HIV-2 in Brazil: epidemiologic perspectives

Em março de 1984 foram realizados, pela primeira vez, no Brasil, inquéritos sorológicos reveladores da presença do HIV-1 (Tabela 1). Em meados de 1986 foram detectados, pela primeira vez, nas Américas, em Säo Paulo, quatro amostras de sangue positivas para o HIV-2 e 28 amostras positivas para ambos os vírus HIV-1 e HIV-2. Cerca de 5.000 casos de AIDS foram notificados até dezembro de 1988, estimando-se em 10 a 15.000 o número real de casos no Brasil. Apresentamos a evoluçäo histórica da origem e disseminaçäo do vírus HIV-2, da Africa para a Europa e América, especulando-se sobre a possível rota, Africa-Brasil do HIV-2. A previsäo sobre a evoluçäo da epidemia de AIDS no Brasil, e por extensäo no Terceiro Mundo, é pessimista, inclusive com a provável imitaçäo do modelo epidemiológico africano da AIDS no País. Além das repercussöes na economia local, säo previstas alteraçöes na patogenia e patologia de várias enfermidades endêmicas da regiäo, tais como Esquistossomose, Doença de Chagas, Tuberculose, Hanseníase, Lishamaniose Viceral, Sarampo, entre outras. Tais alteraçöes säo previstas, em virtude do papel relevante da imunidade mediada por células na evoluçäo das mencionadas doenças

Tratamento de reabilitaçäo: Unidade de Tétano - HCFMUSP / Rehabilitation treatment: Tetanus Unit - HCFMUSP

O tétano é uma doença infecciosa ainda bastante freqüente no nosso meio, com repercussäo severa na área do aparelho locomotor, causando hipertonia muscular acentuada durante a fase aguda e na convalescença. O programa de reabilitaçäo do paciente portador de tétano é iniciado o mais precocemente possível. O objetivo do tratamento é minimizar as complicaçöes osteoarticulares decorrentes do período de imobilizaçäo. A hipertonia generalizada, principalmente dos casos graves, favorece a maior incidência de deformidades. Foram analisados 145 casos, que deram entrada na Unidade de Tétano de JANEIRO DE 1982 à MARÇO DE 1985. Todos esses pacientes receberam tratamento fisiátrico e observou-se que praticamente näo ocorrem complicaçöes decorrentes do período de imobilizaçäo, mesmo nos pacientes mais gravemente acometidos. As complicaçöes osteoarticulares ocorridas foram conseqüentes a dois principais aspectos: 1. Convulsöes tônicas ou espasmos, além é claro, das posturas viciosas mantidas durante períodos prolongados, como o opistótono, que causaram principalmente fraturas dos corpos vertebrais. 2. Complicaçöes decorridas das condiçöes do próprio foco de entrada da doença, levando à infecçöes, tais como osteomielites, pioartrites, infecçöes de tecidos moles, causando assim seqüelas no sistema osteoarticular