Hepatitis: Genovese D

Argentini C, Genovese D, Dettori S, Rapicetta M. · Viral Hepatitis Unit, Department of Infectious, Parasitic & Immune-Mediated Disease, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. · Future Microbiol. · Pubmed #19327119 No free full text.

Abstract: HCV is a ssRNA virus belonging to the Flaviviruses and is found worldwide worldwide in humans. Following primary infection, persistent infection develops in more than 85% of cases, which in up to 30% of cases, may progress to liver disease, cirrhosis and hepatocellular carcinoma. The virus presents a high degree of genetic variability owing to the combination of a lack of proofreading by the RNA-dependent RNA polymerase and a high level of viral replication. This genetic variability allows the classification of genotypes, subtypes, isolates and quasispecies to which epidemiological and pathogenetic significance may be associated. The features and biological implications of HCV variability and of quasispecies dynamics in infection transmission, mechanisms of chronicity and resistance to antiviral therapy are discussed.

Ferraro D, Genovese D, Argentini C, Giordano V, Pizzillo P, Stroffolini T, Craxì A, Rapicetta M, Di Stefano R. · Department of Hygiene and Microbiology, University of Palermo, Palermo, Italy. · J Med Virol. · Pubmed #18712845 No free full text.

Abstract: Several seroepidemiological population-based surveys carried out in Italy have shown a high prevalence of hepatitis C virus (HCV) infection. Camporeale (CP), a small Sicilian town with a 10.4% prevalence of HCV mostly genotype 1b, probably represents a specific context, since intravenous drug addiction, and sexual promiscuity are almost absent. In order to reconstruct the pattern of introduction and diffusion of HCV in this ecological niche, the NS5 genomic region of 72 HCV genotype 1 isolates (39 from CP and 33 collected throughout Sicily) was amplified and sequenced. Sequences were aligned and analyzed by BioEdit, PAUP and BEAST, and their molecular evolution compared. Thirty-eight HCV genotype 1b isolates from CP were associated in a monophyletic "transmission cluster." By applying Monte Carlo Markov simulation, it was calculated that HCV was introduced between the end of the 1940s and the beginning of the 1950s. The phylogenetic distance between the CP cluster and other Sicilian isolates confirmed its uniqueness and the local diffusion from a common ancestor. The data obtained from classic phylogenetic analysis, combined with the application of the Bayesian analysis to the study of the coalescence of phylogenetic trees, have shown that, in CP, few HCV native strains have been transmitted in a limited length of time probably through iatrogenic routes, and then have not spread further.

Pontrelli G, Boccia D, DI Renzi M, Massari M, Giugliano F, Celentano LP, Taffon S, Genovese D, DI Pasquale S, Scalise F, Rapicetta M, Croci L, Salmaso S. · Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Roma, Italy. · Epidemiol Infect. · Pubmed #17892633 No free full text.

Abstract: A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.

Coppola N, Genovese D, Pisaturo M, Taffon S, Argentini C, Pasquale G, Sagnelli C, Piccinino F, Rapicetta M, Sagnelli E. · Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy. · Clin Infect Dis. · Pubmed #17407028 No free full text.

Abstract: BACKGROUND: Acute viral hepatitis due to hepatitis A virus is a self-limited illness that infrequently has a severe clinical course. METHODS: We analyzed the virological characteristics of acute hepatitis A in a patient with a severe clinical presentation (peak total and conjugated bilirubin levels, 65.5 mg/dL and 40.1 mg/dL, respectively) and a course of disease that lasted 7 months. RESULTS: Hepatitis A virus sequencing revealed coinfection with 2 subgenotypes of hepatitis A virus (Ia and Ib) as etiological factors of the illness. CONCLUSIONS: Hepatitis A virus Ia and Ib coinfection may have accounted for the prolonged and severe course of illness.

Kondili LA, Genovese D, Argentini C, Chionne P, Toscani P, Fabro R, Cocconi R, Rapicetta M. · Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. · Eur J Clin Microbiol Infect Dis. · Pubmed #16835740 No free full text.

Abstract: Reported here are details of a simultaneous outbreak of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections that occurred in a hemodialysis centre in northern Italy, with three patients seroconverting for HBsAg and four patients seroconverting for HCV antibodies. Phylogenetic analysis of the E2 region of the isolates from HCV-seroconverted patients showed the sequences were grouped in the same distinct branch as in a chronically HCV-infected patient, suggesting that the chronically infected patient was the index case. For the patients with HBV infection, phylogenetic analysis showed strong clustering among the sequences of the three patients who seroconverted to HBsAg and no relatedness between them and the sequences of patients chronically infected with HBV. For one of the patients who seroconverted to HBsAg, the last test with negative results for HBV markers had been performed 18 months prior to HBsAg seroconversion. This patient may have been previously infected with HBV and is presumed to be the source of the outbreak. This report emphasizes the importance of using universal precaution measures and HBV vaccination to prevent the transmission of viral hepatitis among chronic hemodialysis patients.

Spada E, Genovese D, Tosti ME, Mariano A, Cuccuini M, Proietti L, Giuli CD, Lavagna A, Crapa GE, Morace G, Taffon S, Mele A, Rezza G, Rapicetta M. · Istituto Superiore di Sanità, National Center of Epidemiology, Surveillance and Health Promotion, Clinical Epidemiology Unit, Viale Regina Elena 299, 00161 Rome, Italy. · J Hepatol. · Pubmed #16143420 No free full text.

Abstract: BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS: We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. RESULTS: Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. CONCLUSIONS: HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.

Genovese D, Dettori S, Argentini C, Villano U, Chionne P, Angelico M, Rapicetta M. · Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Disease, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. · J Clin Microbiol. · Pubmed #15815016 links to  free full text

Abstract: We analyzed hepatitis C virus (HCV) genotype 4 isolates circulating in the Alexandria District (Egypt) in terms of genetic divergence and the presence of different subtypes. Hypervariable region 1 (HVR1) and the NH2 region of the E2 protein were characterized, and the heterogeneity of subtype 4a isolates was evaluated by analyzing epitope frequencies, immunoproteasome prediction, and possible glycosylation patterns. The heterogeneity of the nucleotide sequences was greater than that found in previous studies, which reported only subtype 4a. Subtype 4a was most common (78% of cases), yet four new subtypes were found, with subtype 4m representing 11% of the cases and the other three subtypes representing another 11%. Substantial heterogeneity was also found when the intrasubtype 4a sequences were analyzed. Differences in the probability of glycosylation and in the positions of the different sites were also observed. The analysis of the predicted cytotoxic-T-lymphocyte epitopes showed differences in both the potential proteosome cleavage and the prediction score. The Egyptian isolates in our study also showed high variability in terms of the HVR1 neutralization epitope. Five of these isolates showed amino acid substitutions never previously observed (a total of six positions). Four of these residues (in four different isolates) were in positions involved in anchoring to the E2 glycoprotein core and in maintaining the HVR1 conformation. The results of this study indicate that HCV genotype 4 in Egypt is extremely variable, not only in terms of sequence, but also in terms of functional and immunological determinants. These data should be taken into account in planning the development of vaccine trials in Egypt.