The aim of this study was to investigate the relative frequency of hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as well as possible secular changes in their distribution in relation to modes of transmission, age and time at acquisition of the infection and other variables. We evaluated 434 unselected patients, 241 males and 193 females with a median age of 46.2 years (18-75), with chronic HCV infection presenting during the period 1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay. Liver biopsies were evaluated according to Ishak's scoring system. Of 434 patients, 167 had a history of blood transfusion [post-transfusion hepatitis (PTH)], 80 were i.v. drug users and in 187 the route of infection remained unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27 and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug users, whereas genotype 1 predominated in older people and PTH patients (P < 0.001 for both). Infection acquired before 1981 (group A) was related to transfusion and genotype 1, while after 1981 (group B) with i.v. drug use and genotype 3 (P < 0.01). Biopsy was available in 369 (85%) patients, of whom 22.5% had cirrhosis; 29.8% in group A and 9.9% in group B. In a multivariate analysis, cirrhosis was strongly associated with the duration of infection (P = 0.013). Our study revealed a change of HCV genotype distribution in the last 20 years among Greek patients with chronic HCV infection as a result of epidemiological changes in HCV transmission. The presence of cirrhosis was associated only with the duration of infection. These observations have impact both on prevention and treatment.
In this study different forms of the hepatitis C virus (HCV) NS5A protein, including a nearly full-length, an amino-terminal and a carboxy-terminal truncated form were produced in E. coli as fusion proteins with the MBP or the GST protein. The chimeric proteins were tested for their reactivity with sera from HCV infected patients by immunoblot and ELISA assays. A panel of 110 sera specimens, including 39 HCV-positive sera, 27 sera from patients with non-HCV-associated liver disease and 44 healthy individuals were analyzed for the presence of antibodies to NS5A. Twenty four (61 %) out of the 39 HCV positive sera, showed reactivity against the nearly full length NS5A, 21 (54 %) against the amino-terminal part of NS5A and 20 (51 %) against the carboxy-terminal part of the NS5A protein in immunoblot assays, suggesting that immunoreactive epitopes are present both at the carboxy- and the amino- terminal part of the protein. None of the 71 HCV-negative serum samples showed any reactivity against the NS5A antigens. With the exception of one patient, similar data were obtained with an ELISA assay based on the use of the nearly full-length NS5A antigen. The data indicate that new forms of NS5A may be potentially valuable antigens for the development of serological assays for HCV.
A replication-defective herpes simplex virus type 1 (HSV-1) recombinant lacking the glycoprotein H (gH)-encoding gene and expressing a truncated form of the hepatitis C (HCV) E2 glycoprotein (E2-661) was constructed and characterized. We show here that cells infected with the HSV/HCV recombinant virus efficiently express the HCV E2-661 protein. Most importantly, cellular and secreted E2-661 protein were both readily detected by the E2-conformational mAb H53 and despite the high expression levels, only limited amounts of misfolded aggregates were detected in either the cellular or secreted fractions. Furthermore, cell-associated and secreted E2-661 protein bound to the major extracellular loop (MEL) of CD81 in a concentration-dependent manner and both were highly reactive with sera from HCV-infected patients. Finally, BALB/c mice immunized intraperitoneally with the recombinant HSV/HCV virus induced high levels of anti-E2 antibodies. Analysis of the induced immunoglobulin G (IgG) isotypes showed high levels of IgG2a while the levels of the IgG1 isotype were significantly lower, suggesting a Th1-type of response. We conclude that the HSV-1 recombinant virus represents a promising tool for production of nonaggregated, immunologically active forms of the E2-661 protein and might have potential applications in vaccine development.
INTRODUCTIONChronic hepatitis C is a severe health problem affecting a signi®cant proportion of the population world-wide, compromising quality of life and, if not treated in time, potentially leading to death.1±3 Since a vaccine has not yet been developed, most clinical efforts are being concentrated on therapy. The standard scheme with interferon-a (IFN-a) monotherapy, 3 million units (MU) three times a week for 1 year, has an overall sustained ef®cacy of less than 25%. 4±12 Even with the present optimal treatment with a combination of interferon and ribavirin, the response rates are not particularly high, while the side-effects become more severe.13, 14 Daily administration of IFN has been tried in the past in clinical trials, particularly from Japan, with promising results, but its ef®cacy compared to that of the conventional three-times-a-week schemes has hitherto remained unknown. Recent data from viral kinetic studies have renewed the clinical interest in daily IFN administration, suggesting that daily dosing of IFN-a during the initial period of treatment of chronic hepatitis C results in a faster and more frequent initial response rate compared to the same dose given three times a week. 15±17 However, because many different types of IFN, various doses and durations of daily administration of IFN have been tried, little can be deduced on the longterm ef®cacy of such treatment schemes. 9, 18±28
Data on BacT/Alert blood cultures in a Greek hospital from 1995 to 2002 were analysed retrospectively. There was a gradual increase in the number of blood cultures (4981 in 1995 to 9054 in 2002), the true positive rate (14.4% to 16.5%) and the number of bloodstream infections/1000 hospital admissions (22.1 to 30.7). The five most common pathogens were Eschericia coli, Staphylococcus aureus, coagulase-negative staphylococci, enterococci and Klebsiella spp. The relative rates of Gram-negative and Gram-positive isolates inverted during the study period because of an increasing frequency of coagulase-negative staphylococci and enterococci.
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