Introduction:A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients.Material and methods:Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters.Results:A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p < 0.001). The degree of fibrosis increased with advancing age. Only age at diagnosis and fasting blood glucose were independently associated with disease stage. Those patients with subtype 1a had higher prevalence of F2–F4 than those with subtype 1b.Conclusion:In Brazil, diagnosis of hepatitis C is more commonly established in older patients (age 45–60 years) with more advanced disease. Reassessment of strategies for hepatitis C diagnosis in the country is required.

OBJETIVO: Revisar a importância da resistência insulínica no desenvolvimento da hepatite C crônica e sua interferência na resposta ao tratamento antiviral de pacientes infectados pelo vírus da hepatite C. FONTE DE DADOS: Revisão bibliográfica de trabalhos publicados pelo MEDLINE e dados dos próprios autores. SÍNTESE DE DADOS: Nos últimos anos, grande número de publicações tem demonstrado importante associação entre resistência insulínica e hepatite C crônica. Aumento na prevalência de diabetes mellitus tipo 2, desenvolvimento de esteatose hepática (principalmente nos pacientes com infecção pelo genótipo não-3), progressão mais rápida da doença e redução na taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina, têm sido todos associados à presença de resistência insulínica nos pacientes infectados pelo vírus da hepatite C. A produção aumentada de fator de necrose tumoral pelo core do vírus da hepatite C é o principal mecanismo responsável pelo aparecimento da resistência insulínica. O fator de necrose tumoral afetaria a fosforilação do substrato do receptor de insulina diminuindo a captação de glicose e acarretando hiperinsulinemia compensatória. Aumento da siderose hepática e alterações dos níveis circulantes das adipocitocinas podem ter efeito adicional sobre a sensibilidade à insulina na hepatite C crônica. CONCLUSÕES: O diagnóstico e o tratamento da resistência insulínica nesses pacientes podem não só evitar o aparecimento das complicações, mas também prevenir a progressão da doença e, possivelmente, aumentar a taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina.

OBJECTIVE: To revise the importance of insulin resistance in the development of chronic hepatitis C and its interference in the response to the antiviral treatment of these patients. DATA SOURCE: Bibliographic revision of published papers in the MEDLINE and the authors’ data. DATA SYNTHESIS: In the last years several published papers have demonstrated an important relationship between insulin resistance and chronic hepatitis C. Increased prevalence of type 2 diabetes mellitus, the development of hepatic steatosis (specially in non-3 genotype), a more rapid progression of hepatic disease and reduction in the sustained virological response to treatment with pegylated interferon plus ribavirin have been associated with insulin resistance in patients infected with HCV. The mechanism implied in the insulin resistance is the enhanced production of tumor necrosis factor by the HCV core. Tumor necrosis factor affects insulin receptor substrate phosphorylation, resulting in decreased glucose uptake and compensatory hyperinsulinemia. Increased liver iron accumulation and modification in the levels of adipocytokinemia can have an additional effect on insulin sensitivity in chronic C hepatitis. CONCLUSIONS: Diagnosing and treating insulin resistance in patients with chronic hepatitis C could not only avoid complications but also prevent disease progression and increased the sustained virological rate to treatment with pegylated interferon plus ribavarin.

INTRODUÇÃO: A crioglobulinemia mista (CM) representa importante complicação extra-hepática da hepatite C. Nesse estudo avaliamos sua prevelência em pacientes com hepatite C crônica (HCC) e relacionamos sua presença com aspectos clínicos e resposta ao tratamento com interferon alfa e ribavirina. CASUÍSTICA E MÉTODOS: 202 pacientes consecutivos com HCC (136 com hepatite crônica e 66 com cirrose) foram avaliados para a presença de CM. Os crioprecipitados foram caracterizados por imunoeletroforese e classificados de acordo com BROUET et al. RESULTADOS: A prevalência de CM nessa população foi de 27% (54/202), e, desses, 24% (13/54) apresentaram manifestações clínicas maiores da doença. Embora MC tipo III tenha sido a forma mais freqüentemente encontrada, a doença sintomática foi mais comum entre os pacientes com MC tipo II. A presença de cirrose (RR = 2,073; IC95% = 1,029 - 4,179; p = 0,041) e a idade do paciente (RR = 1,035; IC95% = 1,008 - 1,062; p = 0,01) estiveram independentemente associadas à presença de CM. Não houve associação entre a presença de CM e genótipo ou carga viral do vírus C. No total, 102 pacientes foram tratados com interferon alfa e ribavirina. Desses, 31 apresentavam CM. A resposta virológica sustentada (em torno de 30%) não diferiu entre pacientes com e sem CM (p = 0,971). CONCLUSÃO: CM é uma freqüente complicação na HCC, especialmente em pacientes com idade avançada e com cirrose hepática. Apenas 24% desses pacientes apresentam manifestações clínicas da doença, sendo mais freqüentes entre portadores de CM tipo II. A presença de crioglobulinemia não afetou a resposta virológica ao tratamento com interferon alfa e ribavirina.

INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS: The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR = 2.073; IC95% = 1.029 - 4.179; p = 0.041), and age of the patients (RR = 1.035; IC95% = 1.008 - 1.062; p = 0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p = 0.971). CONCLUSION: MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.

The combined therapy with interferon alfa plus ribavirin (INF+RBV) is considered the most appropriate treatment for patients with chronic hepatitis C virus genotypes 2 and 3 in Brazil. However, wide variations in the rates of sustained viral response (SVR) have been reported among such patients. We evaluated, retrospectively, factors associated with SVR in subjects with chronic hepatitis C virus genotypes 2 and 3 and that received medication from the Health Secretariat of the state of São Paulo. One-hundred-seventy-seven consecutive patients with chronic hepatitis C were treated for 24 or 48 weeks according to the viral genotype. Patients co-infected with associated hepatic diseases or who had problems with alcohol abuse were excluded. The genotype of the HCV-RNA was identified through restriction analysis, the viral load through quantitative PCR (Amplicor, Roche) and the degree of hepatic fibrosis according to the Metavir score. Demographic, virological and histological parameters were submitted to binary logistic regression analysis to identify the variables associated with SVR. The overall rate of SVR was 36.4% for the 177 patients, and genotype 2 or 3 was the main parameter independently associated with SVR. Among the 77 patients with these viral genotypes, only the stage of fibrosis had a significant effect on the SVR (odds ratio (OR) = 3.035; 95% CI (confidence interval) = 1.196-7.699; p=0.019). The rate of SVR among the subjects with fibrosis at an advanced stage (F3-F4) was 38%, compared to 75% for patients with fibrosis at an initial stage (F0-F2). Consequently, other therapeutic options should be considered for patients with genotypes 2 and 3 who have advanced fibrosis.