Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia Brazil.

UNLABELLED: Hepatitis C virus displays a high degree of genetic mutation, with considerable heterogeneity, motivating clinical and biomolecular investigations. It is necessary to understand the effects of genotypes on the course of the disease, as well as their peculiarities at the regional level. OBJECTIVE: The study objective was to compare epidemiological, biochemical and histological aspects of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia. STUDY DESIGN: Data were collected retrospectively from outpatient medical records. MATERIALS AND METHODS: 127 patients with positive anti-HCV results were selected, based on detectable RNA-HCV (RT-PCR) of genotypes 1a, 1b and 3a. RESULTS: Thirty-nine (30.7%) individuals were infected by subtype 1a, 45 (35.4%) by subtype 1b and 43 (33.9%) by subtype 3a. Most (73.2%) patients were male, with an average age of 47.8 years. The subtype 1b-infected patients had the highest average age (512 +/-11.17; P=0.09). The use of illicit injected drugs was more frequent among subtype 3a infected individuals when compared with genotype 1 (6/43; 14% and 3/84; 3.6%, respectively; P=0,06). No significant differences were found for other epidemiological characteristics. Average values for GT, AST, ALT and ferritin did not differ between the groups (64, 78, 109, 276, respectively). Thyroid dysfunction occurred in 7/30 (23.3%) of those infected by genotype 3 (P=0.05). Cryoglobulinemia was also more frequent in this group (5/13, 38%, P=0.02). Most patients presented limited necro-inflammatory activity, stages 2 and 3 by the METAVIR Classification. In some cases, dissociation was noticed between inflammatory activity and fibrosis. No significant differences were found in the histopathological findings of the various genotypes. Younger patients had a significantly smaller degree of necrosis in stomatocytosis (P=0.032) and fibrosis (P=0.012). Intense parenchymatous activity and lymphoid follicles were more frequent among alcohol consumers (P=0.06 and P=0.04, respectively). CONCLUSIONS: In Bahia, genotype 3 dissemination seems to be associated with illicit drug use. The disease evolution depends on a function of complex interactions between virus and host. Age and alcohol consumption stand out as important variables in the development of cirrhosis.

Immune responses against hepatitis C virus structural proteins following genetic immunisation.

We have used direct DNA inoculation to study the in vivo induction of both humoral and cellular immune responses to hepatitis C virus (HCV) encoded structural antigens. Following immunisation of mice, immune responses were compared using plasmids encoding full-length or partial HCV gene sequences for the nucleocapsid and envelope E2 proteins. Plasmids encoding secreted or non-secreted forms of the immunogens, including constructs expressing HCV sequences fused with the hepatitis B virus surface antigen (HCV-HBV chimeras), were evaluated. Results indicate that: (i) all constructs induced specific anti-HCV antibodies; (ii) antibody titres ranged from 1:100 to > 1:100,000; (iii) all HCV DNA immunogens induced a predominant Th1 response with the induction of IgG2a antibodies; (iv) the secretion level of the antigens and immune responses was not always correlated and (v) CTL could be detected against both HCV and HBV determinants.

Treatment of polyarteritis nodosa related to hepatitis B virus with short term steroid therapy associated with antiviral agents and plasma exchanges. A prospective trial in 33 patients.

OBJECTIVE: To test the effectiveness and tolerance of antiviral agents associated with short term immunosuppression in the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS: We conducted a prospective, nonblinded, multicenter trial in which patients with multisystemic PAN related to HBV were included. Every patient initially underwent a short term (2 weeks) treatment with prednisone and then received vidarabine (Vira A) and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Thirty-three patients were included. Every patient had histopathologic or arteriographic evidence of vasculitis and was infected with actively replicating HBV. Disease activity during the first 6 months was controlled in 26 patients (78.8%). Among the 25 patients still alive at the end of the study, 24 (72.7%) had completely recovered with no clinical or laboratory evidence of systemic vasculitis after at least 18 months without treatment. Eight patients died during the study period; 3 of treatment failure, usually early in the course of the disease. One patient died of fulminant hepatitis 3 months after the entry in the study at time of seroconversion. The survival curve showed that at 7 years, 76% of the patients were alive. HBeAg/anti-HBeAb seroconversion was observed in 12 patients (36.3%) after one Vira A cycle. When a 2nd cycle of Vira A or alpha interferon was prescribed, HBeAg/anti-HBeAg seroconversion occurred in 15 patients (45.4%). Two other patients who underwent a 2nd cycle of Vira A administration, had lost HBeAg and no longer expressed serological evidence of replication as assessed by HBV DNA spot hybridization. At the end of the study, 17 (51.5%) no longer expressed serological evidence of HBV replication. This treatment was effective and only minor side effects were noted. CONCLUSIONS: We conclude that this new therapeutic approach to PAN related to HBV effectively controlled systemic vasculitis and was associated with a higher number of recoveries from chronic HBV infections. The development of new antiviral agents, such as interferon alpha 2b, allows us to hope that antiviral therapy will have a role to play as a first line treatment regimen of virus induced vasculitis.