In 1996 the prevalence, risk factors, and genotype distribu-subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These tion of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individwas selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the uals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general popula-(11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-con-tion with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epifirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to demic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the 33.1% in those ¢60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease. tested positive more frequently than males (14.1% vs. 10.5%; P õ .05). Alanine transaminase (ALT) concentrations were (HEPATOLOGY 1997;26:1006-1011.) abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening Hepatitis C virus (HCV) infection represents a major is not useful in the detection of anti-HCV-positive subjects health problem in Italy. It has been found to be highly prevain a general population. The results of multiple logistic regreslent in subjects with chronic liver disease 1-2 and strongly sion analysis showed that an age of less than 45 years, the associated with hepatocellular carcinoma. 3-4 use of glass syringes, and dental therapy were all independent General population surveys in different countries that depredictors of anti-HCV positivity. HCV RNA was detected by termined the prevalence of hepatitis C virus antibodies (antipolymerase chain reaction in 75.9% of the 195 anti-HCV EIA-HCV) have mainly consisted of voluntary or paid blood positive subjects: in 84.7% (144/170) of the RIBA-confirmed donors. Because these populations usually have special charsubjects; in 17.4% (4/23) tested as RIBA indeterminate; and acteristics regarding age, ...
Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1–B5) that interact with the variable domain of Ig κ L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1–B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (rs = 0.82; p < 0.001) between the maximal percent IL-4 release induced by protein L and that induced by anti-IgE and between intact protein L and the B1–B4 fragment (rs = 0.90; p < 0.01). Removal of IgE bound to basophils markedly reduced the IL-4 release induced by anti-IgE, protein L, and B1–B4. Preincubation of basophils with protein L or anti-IgE caused complete cross-desensitization to subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (λ chains) blocked anti-IgE-induced IL-4 release, but not the releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (κ chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with κ L chains of the IgE isotype.
The results indicate that host factors impose selective constraints on the evolution of the HIV-1 structures involved in viral entry. In LTNP, these factors are likely to force the virus into attenuated variants.
The mean prevalence of anti-hepatitis C virus (HCV) in Italy is 0.87%. It reaches 2% in Campania, Southern Italy. Approximately 50% of community acquired non-A, non-B (NANB) hepatitis cannot be associated with known parenteral exposure. A recent Italian study has shown that the only demonstrable risk factor in 9% of acute C/NANB hepatitis is dental treatment. There are no data on direct contamination by HCV of dental surgeries. Possible environmental contamination by HCV-RNA was investigated in dental surgeries after treatment of anti-HCV and HCV-RNA positive patients. Thirty-five anti-HCV and HCV-RNA positive patients with chronic hepatitis underwent dental treatment and were enrolled in this study. Eight had chronic persistent hepatitis (CPH), 23 chronic active hepatitis (CAH), and 4 cirrhosis. A total of 328 samples collected from instruments and surfaces were tested after dental treatment of 35 anti-HCV positive patients. The presence of HCV-RNA was determined by polymerase chain reaction (PCR) to evaluate contamination of instruments and surfaces in dental surgeries. Twenty (6.1%) out of 328 collected samples were positive for HCV-RNA. The positive samples were from work benches (two), air turbine handpieces (one), holders (four), suction units (one), forceps (four), dental mirrors (two), and burs (six). Our data indicate that there is extensive contamination by HCV of dental surgeries after treatment of anti-HCV patients and that if sterilisation and disinfection are inadequate there is the possible risk of transmission to susceptible individuals.
The hypervariable region 1 (HVR-1) of the putative envelope encoding E2 region of hepatitis C virus (HCV) RNA was analyzed in sequential samples from three patients with acute type C hepatitis infected from different sources to address (i) the dynamics of intrahost HCV variability during the primary infection and (ii) the role of host selective pressure in driving viral genetic evolution. HVR-1 sequences from 20 clones per each point in time were analyzed after amplification, cloning, and purification of plasmid DNA from single colonies of transformed cells. The intrasample evolutionary analysis (nonsynonymous mutations per nonsynonymous site [Ka
], synonymous mutations per synonymous site [Ks
],Ka
/Ks
ratio, and genetic distances [gd]) documented low gd in early samples (ranging from 2.11 to 7.79%) and a further decrease after seroconversion (from 0 to 4.80%), suggesting that primary HCV infection is an oligoclonal event, and found different levels and dynamics of host pressure in the three cases. The intersample analysis (pairwise comparisons of intrapatient sequences; rKa
, rKs
, rKa
/rKs
ratio, and gd) confirmed the individual features of HCV genetic evolution in the three subjects and pointed to the relative contribution of either neutral evolution or selective forces in driving viral variability, documenting that adaptation of HCV for persistence in vivo follows different routes, probably representing the molecular counterpart of the viral fitness for individual environments.
There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.
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