Luis Jesuino de Oliveira Andrade

Association between hepatitis C and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis.

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

OBJECTIVE To investigate the frequency of thyroid disorders (TD) in patients with chronic hepatitis C before and during interferon-alpha (IFN-α) and ribavirin (RIB) treatment. STUDY DESIGN Prospective study. PATIENTS AND METHODS We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of treatment. RESULTS Mean age of the 65 patients (38 females and 27 males) was 49.61 ± 11.83 years. Seven (10.76%) patients presented baseline thyroid disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92%) patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A total of 18 patients (27.69%) developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6), hyperthyroidism 1.2 (95% CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5). The study showed a significant association between female sex and thyroid disease (p = 0.009). CONCLUSION Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

Pigmentary retinopathy due to Bardet-Biedl syndrome: case report and literature review

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical and genetic heterogeneity. This syndrome was first described by Laurence and Moon in 1866 and additional cases were described by Bardet and Biedl between 1920 and 1922. The main features are obesity, polydactyly, pigmentary retinopathy, learning disabilities, various degrees of intellectual impairment, hypogonadism, and renal abnormalities. Bardet-Biedl syndrome is both phenotypically and genetically heterogeneous. Clinical diagnosis is based on the presence of 4 of the 5 cardinal features. The authors present a typical case of pigmentary retinopathy due to Bardet-Biedl syndrome and made a brief commentary about the diseases cardinal manifestations.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

Detecção do hipotireoidismo subclínico em gestantes com diferentes idades gestacionais

AIM To detect subclinical hypothyroidism in pregnant women. SUBJECTS AND METHODS Seventy-five pregnant women who resided in the town of Itabuna, state of Bahia, were voluntarily studied. Inclusion criteria were age < 40 years, no history of previous thyroid disease, autoimmunopathy or diabetes mellitus, and any gestational age; a clinical evaluation (an interview obeying to a questionnaire); laboratory evaluation (free T4, TSH, anti-TPO antibody, total and HDL cholesterol, triglyceride determinations); thyroid ultrasonography. RESULTS Average age was 21.6 +/- 5.1 (14-40 years); gestation age was 24.2 +/- 8.2 (5-39 weeks); an elevated TSH with normal free T4 was found in 3 cases (4.0%). Anti-TPO antibodies were positive in 8.0% on the pregnant women. In 5.4% of them, thyroid ultrasonographic changes were documented. CONCLUSION Based on finding of a 4% prevalence of elevated TSH during pregnancy, the authors consider important the inclusion of thyroid function laboratory evaluation in the routine prenatal examination. Further studies appear necessary to establish at what gestational age thyroid function evaluation should be started in pregnant women and how frequently it should be repeated during the course of gestation.

Cintilografia de perfusão miocárdica em pacientes diabeticos tipo 2 com dor torácica atípica

Foram avaliados atraves de cintilografia miocardica de perfusao, 67 pacientes com diabetes tipo 2 (DM2) com dor toracica atipica e com eletrocardiograma de repouso normal ou com alteracoes inespecificas da repolarizacao ventricular, com o objetivo de se verificar a prevalencia de alteracoes miocardicas isquemicas. A idade media ± DP dos pacientes foi de 63,5 ± 9 anos. Vinte e um (31,3%) homens e 46 (68,7%) mulheres. Grande parte da amostra (62,7%) apresentou exame normal, enquanto em 37,3% a cintilografia apresentou-se positiva para isquemia. O teste ergometrico foi realizado em 91% (n = 61) e em 31,1% foi positivo para isquemia. A concordância entre a cintilografia miocardica e o teste ergometrico mostrou baixa correlacao entre os dois testes (Kappa = 0,49; P = 0,0001). Concluimos que a cintilografia de perfusao miocardica comprovou-se de elevado valor clinico na avaliacao e diagnostico da doenca coronariana em pacientes com DM2 com dor precordial atipica.

SEQUENCE SIMILARITY BETWEEN THYROID SELF-PROTEIN AND HEPATITIS C VIRUS POLYPROTEIN: possible triggering mechanism of autoimmune thyroiditis

BACKGROUND - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. OBJECTIVE - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. METHODS - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. RESULTS - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). CONCLUSION - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.

Interferon-alfa: um disruptor endócrino?

, edicao de dezembro de 2010, a Dra. Clarisse M. M. Ponte e cols. apresentaram uma excelente revisao sobre “Disturbios metabolicos em doencas infecciosas emergentes e negligenciadas”. Nesta revisao, os autores apresentam as mais frequentes doencas infecciosas e sua as-sociacao, em especial, com o diabetes melito tipo 2 (DM2).Em relacao as hepatites virais, deve-se ter especial atencao a hepatite C cronica (HCC) e seu tratamento, tendo em vista a importância de eventos metabolicos na fisiopatologia da infeccao pelo virus da hepatite C (VHC) cada vez mais aparente, que representa uma importante classe de manifestacoes endocrinas VHC-relacionada.A Organizacao Mundial da Saude estima que cerca de 3% da populacao mundial esteja infectada com o VHC (1). Interferon-alfa (IFN-α) e atualmente o tratamento padrao em individuos com infeccao pelo VHC, e as disfuncoes endocrinas tem sido relatadas durante seu uso, de forma que o IFN-α poderia ser considerado um interfe-rente endocrino (IE) (2).E importante conhecer as interacoes entre as citocinas e o sistema endocrino, para assim compreender os mecanismos de desenvolvimento dos eventos endocrinologi-cos, quando do uso do IFN-α, bem como em endocrinopatias autoimunes. Os estu-dos publicados demonstram o potencial patogenico do IFN-α para autoimunidade, embora esteja evidente que fatores geneticos e ambientais tambem sejam essenciais para o desenvolvimento das doencas autoimunes.Evidencias da associacao entre as alteracoes hipotalâmicas e a infeccao pelo VHC estao relacionadas ao tratamento com o IFN-α. Os interferons podem modular direta-mente ou por meio da inducao de outras citocinas a funcao do eixo hipotalâmico (3). Entretanto, os dados ainda permanecem contraditorios sobre a disfuncao do hipotala-mo em portadores de HCC em tratamento com IFN-α, sendo um campo importante para futuras pesquisas.Recentes pesquisas sugerem que a hipofise e potencialmente um dos sitios prima-rios do sistema neuroendocrino alterado pelo IFN-α. Doencas hipofisarias e infeccao pelo VHC sao relacionadas ao tratamento com IFN-α. Evidencias demonstram que o IFN-α pode desempenhar um papel regulador da secrecao de hormonio do cres-cimento, com efeitos estimulantes e inibitorios sobre a secrecao desse hormonio (4). Os efeitos do tratamento com IFN-α sobre o hormonio luteinizante e o foliculo es-timulante nao levam a qualquer alteracao sobre seus niveis plasmaticos, entretanto o IFN-α induz a uma reducao aguda dos niveis sericos dos androgenos e da testosterona livre (5). A concentracao serica de prolactina (PRL) em homens com HCC apresenta um aumento importante e tambem tem sido relatado que o IFN-α tem um efeito inibitorio dose-dependente sobre a PRL em individuos com adenoma hipofisario (6).

Polimorfismo do promotor -308 do fator de necrose tumoral alfa e resistência à insulina em adolescentes com sobrepeso e obesidade

Study Model/Methodology: This is a cross-sectional study with a sample of 104 overweight/obese adolescents, with a mean weight of 52.98 kg ± 22.00, mean age 16.01 ± 2.91 years. We used the homeostasis model assessment-estimated IR (HOMA-IR) index to quantify the insulin resistance (IR). The -308 polymorphism of the promoter of TNF-α was performed using polymerase chain reactionrestriction fragment length polymorphism technique. Statistical analysis of the quantitative measures was conducted with a student’s t-test. For correlation between the genotype and alleles, we used chisquare statistical test. To test the heterogeneity between HOMA-IR and the anthropometric parameters the Mann-Whitney test was used, associated with the Hardy-Weinberg equilibrium. The association between -308G/A polymorphism of the promoter of TNF-α and HOMA-IR was tested by univariate linear regression analysis. Objective: Investigate the association between -308G/A polymorphism in the promoter of tumor necrosis factor-alpha (TNF-α) and susceptibility to IR in overweight/obese adolescents. Results: The prevalence of IR was 18.30% according to the HOMA-IR. The frequency of GG, AG and AA genotype was found 75 (72.12%), 28 (26.92%) and 1.0 (0.96%) respectively. Allele frequencies for guanine (G) and adenine (A) were 178 (85.58%) and 30 (14.42%), respectively. The allele A as well as GA and AA genotype contributed to increase RI (14.42% and 27.88% respectively). Conclusion: The - 308 G/A polymorphism of the promoter of TNF-α can contribute to the IR increase in obese adolescents with GA and AA genotypes.Study Model/Methodology: This is a cross-sectional study with a sample of 104 overweight/obese adolescents, with a mean weight of 52.98 kg ± 22.00, mean age 16.01 ± 2.91 years. We used the homeostasis model assessment-estimated IR (HOMA-IR) index to quantify the insulin resistance (IR). The -308 polymorphism of the promoter of TNF-α was performed using polymerase chain reactionrestriction fragment length polymorphism technique. Statistical analysis of the quantitative measures was conducted with a student’s t-test. For correlation between the genotype and alleles, we used chisquare statistical test. To test the heterogeneity between HOMA-IR and the anthropometric parameters the Mann-Whitney test was used, associated with the Hardy-Weinberg equilibrium. The association between -308G/A polymorphism of the promoter of TNF-α and HOMA-IR was tested by univariate linear regression analysis. Objective: Investigate the association between -308G/A polymorphism in the promoter of tumor necrosis factor-alpha (TNF-α) and susceptibility to IR in overweight/obese adolescents. Results: The prevalence of IR was 18.30% according to the HOMA-IR. The frequency of GG, AG and AA genotype was found 75 (72.12%), 28 (26.92%) and 1.0 (0.96%) respectively. Allele frequencies for guanine (G) and adenine (A) were 178 (85.58%) and 30 (14.42%), respectively. The allele A as well as GA and AA genotype contributed to increase RI (14.42% and 27.88% respectively). Conclusion: The - 308 G/A polymorphism of the promoter of TNF-α can contribute to the IR increase in obese adolescents with GA and AA genotypes.Study Model/Methodology: This is a cross-sectional study with a sample of 104 overweight/obese adolescents, with a mean weight of 52.98 kg ± 22.00, mean age 16.01 ± 2.91 years. We used the homeostasis model assessment-estimated IR (HOMA-IR) index to quantify the insulin resistance (IR). The -308 polymorphism of the promoter of TNF-α was performed using polymerase chain reactionrestriction fragment length polymorphism technique. Statistical analysis of the quantitative measures was conducted with a student’s t-test. For correlation between the genotype and alleles, we used chisquare statistical test. To test the heterogeneity between HOMA-IR and the anthropometric parameters the Mann-Whitney test was used, associated with the Hardy-Weinberg equilibrium. The association between -308G/A polymorphism of the promoter of TNF-α and HOMA-IR was tested by univariate linear regression analysis. Objective: Investigate the association between -308G/A polymorphism in the promoter of tumor necrosis factor-alpha (TNF-α) and susceptibility to IR in overweight/obese adolescents. Results: The prevalence of IR was 18.30% according to the HOMA-IR. The frequency of GG, AG and AA genotype was found 75 (72.12%), 28 (26.92%) and 1.0 (0.96%) respectively. Allele frequencies for guanine (G) and adenine (A) were 178 (85.58%) and 30 (14.42%), respectively. The allele A as well as GA and AA genotype contributed to increase RI (14.42% and 27.88% respectively). Conclusion: The - 308 G/A polymorphism of the promoter of TNF-α can contribute to the IR increase in obese adolescents with GA and AA genotypes.