[en] In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

[en] To determine an association between transmission of hepatitis B virus and secretor and non-secretor status of salivary blood group antigens. Study Design: Cross-sectional, analytical study. Place and Duration of Study: The Department of Physiology and Division of Hepatology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia, from 2007 to 2009. Methodology: Eighty eight known patients, who were positive for Hepatitis B Surface Antigen [HBsAg] were recruited. Saliva was collected for investigating the secretor and non-secretor status by using blood typing kit number Kemtec Educational Science USA. Hepatitis B Surface antigen test was performed on Enzyme Linked Immunosorbent Assay technique. Polymerase chain reaction [PCR] on saliva was also carried out in High Performance Thermal Cycler-Palm- Cycler [Corbett Life Science, Sydney, Australia] and enzymatic amplification of extracted viral DNA was performed using primers covering the promoter of the core region of HBV. Results: Out of the 88 subjects, 61 belong to blood group O, 20 to A and 7 subjects to blood group B. Fifty subjects were secretors [salivary blood group antigens positive] and 38 subjects were non-secretors [salivary blood group antigens negative]. Among core gene positive 25 (69.4%) were secretors and 11 (30.6%) were non-secretors. However, in core gene negative 25 (48.1%) were secretors and 27 (51.9%) were non-secretors. Conclusion: The result shows an association [p=0.047] between secretor and non-secretors status of the salivary blood group antigens with core gene positive and core gene negative. (author)

[en] Despite the availability of a safe and efficacious vaccine, new cases of infection by hepatitis B virus (HBV) still occur at a substantial rate. This increases the current prevalence of chronic HBV carriers (10% of newly infected subjects) and in the long run, will raise the incidence of chronic liver disease. The surveillance of viral hepatitis commenced in December 1990 by the French sentinel network for electronic surveillance of communicable diseases. Between 1991 and 1996, a decrease in the annual incidence was observed although it was not significant (p=0.06). The mean number of cases for this period was 12 per 100,000 inhabitants. The sex ratio (M/F) was 1.6 (p<0.01) and the median age, 32 years. Heterosexual transmission was suspected in 25% of cases, homo- bisexual transmission in 10%, use of injected drugs in 19%, percutaneous exposure in 9%, and blood transfusion or hemodialysis in 6%. Although the incidence of HBV infection is decreasing, the prevalence of chronic infection will continue to rise. However, the universal hepatitis B immunisation strategy proposed by WHO will dramatically limit the expansion of the population of chronically infected subjects if high coverage is achieved rapidly

[en] Small interfering RNA (siRNA) is currently being evaluated not only as a powerful tool for functional genomics, but also as a potentially promising therapeutic agent for cancer and infectious diseases. Inhibitory effect of siRNA on viral replication has been demonstrated in multiple pathogenic viruses. However, because of the high sequence specificity of siRNA-mediated RNA degradation, antiviral efficacy of siRNA directed to viral genome will be largely limited by emergence of escape variants resistant to siRNA due to high mutation rates of virus, especially RNA viruses such as poliovirus and hepatitis C virus (HCV). To investigate the therapeutic feasibility of siRNAs specific for the putative cellular cofactors for HCV, we constructed adenovirus vectors expressing siRNAs against La, polypyrimidine tract-binding protein (PTB), subunit gamma of human eukaryotic initiation factors 2B (eIF2Bγ), and human VAMP-associated protein of 33 kDa (hVAP-33). Adenoviral-mediated expression of siRNAs markedly diminished expression of the endogenous genes, and silencing of La, PTB, and hVAP-33 by siRNAs substantially blocked HCV replication in Huh-7 cells. Thus, our studies demonstrate the feasibility and potential of adenoviral-delivered siRNAs specific for cellular cofactors in combating HCV infection, which can be used either alone or in combination with siRNA against viral genome to prevent the escape of mutant variants and provide additive or synergistic anti-HCV effects

[en] The hepatitis A virus 3C protease and 3D RNA polymerase are present in low concentrations in infected cells. The 3C protease was previously shown to be rapidly degraded by the ubiquitin/26S proteasome system and we present evidence here that the 3D polymerase is also subject to ubiquitination-mediated proteolysis. Our results show that the sequence ₃₂LGVKDDWLLV₄₁ in the 3C protease serves as a protein destruction signal recognized by the ubiquitin-protein ligase E3α and that the destruction signal for the RNA polymerase does not require the carboxyl-terminal 137 amino acids. Both the viral 3ABCD polyprotein and the 3CD diprotein were also found to be substrates for ubiquitin-mediated proteolysis. Attempts to determine if the 3C protease or the 3D polymerase destruction signals trigger the ubiquitination and degradation of these precursors yielded evidence suggesting, but not unequivocally proving, that the recognition of the 3D polymerase by the ubiquitin system is responsible

[en] Hepadnavirus DNA polymerase functions in DNA synthesis and encapsidation, and acts as a primer for minus-strand DNA synthesis. Through protein priming reaction, a short DNA oligomer synthesized from the bulge of epsilon (ε) as template is covalently attached to the Tyr residue in the terminal protein (TP) domain of DNA polymerase. Using endogenous polymerase assays and native agarose gel analysis, we detected endogenous polymerase activity in priming-deficient mutant core particles, but not in reverse transcriptase (RT) reaction- or P protein-deficient mutant core particles. In addition, priming-deficient mutant core particles incorporated radiolabeled ³²P-dATP, ³²P-TTP, and ³²P-dGTP, but not ³²P-dCTP. Our results suggest that the priming-deficient mutant P protein has the ability to synthesize oligomers (presumably nascent minus-strand DNA) in the absence of covalent linkage between TP and the first deoxynucleotide. We propose that the priming-deficient mutant may be defective in minus-strand DNA translocation to direct repeat (DR) 1 at the 3' end of pregenomic RNA (pgRNA) that leads to the elongation of minus-strand DNA

[en] Purpose: To include biologic factors in parallel-architecture normal-tissue complication probability (NTCP) model for radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy (3D-CRT) for gastric or hepatic cancer. Methods and Materials: A total of 151 patients (89 with hepatocellular carcinoma and 62 with gastric cancer) who received 3D-CRT to the liver were included (isocenter dose range 33.0 to 66.0 Gy; mean 48.0 Gy). RILD was defined as grade 3 or higher liver toxicity according to Common Toxicity Criteria Version 2.0 of the National Cancer Institute within 4 months after 3D-CRT. Possible correlations of patient-related or dosimetric factors with RILD were tested. Maximum-likelihood analysis estimated NTCP model parameters for group and subgroups. Goodness-of-fit analysis estimated deviance of NTCP model parameters between subgroups. Results: RILD developed in 25 patients. Hepatitis B virus carrier status (p < 0.001) was the only significant independent factor. The 4 parallel NTCP model parameters, mean functional reserve (V₅₀), width of functional reserve distribution (σ), dose damage to 50% of liver subunits (D₅₀), and slope parameter for subunit dose-response (k), were respectively, 0.54, 0.14, 50 Gy, 0.18 (group); 0.53, 0.07, 50 Gy, 4.6 x 10^-7 (carriers); 0.59, 0.12, 25 Gy, 59.8 (noncarriers). In carrier-state subgroups, goodness-of-fit deviance with 1 subgroup's parameter set would have been worse in the other group. Across subgroups, patients with RILD all had liver fraction damage (f) greater than 0.4 compared with wider distribution for the whole group. Conclusions: RILD is described with a parallel-architecture NTCP model for HBV carriers and noncarriers with a threshold effect greater than 0.4. The main difference is in slope parameter for subunit dose-response

[en] Viral hepatitis A (VHA) is an acute inflammatory liver disease caused by the primary hepatotropic viruses of hepatitis A. The incidence of the disease 13,83 cases/100 000 inhabitants was reported in the Slovak Republic in 2008. Prolonged or relapsing disease lasting as long as 6 months can occur. Fulminant hepatitis is rare but is more common in people with underlying liver disease and in pregnant women. Chronic infection does not occur. Despite the fact that VHA is a self-limited disease having regular mild course, its epidemic occurrence represents/denotes a serious socio-economic problem in areas inhabited by the population of lower hygienic and social standards. At the present time, the disease can be prevented by the vaccination. (author)

[en] Background: Hepatitis C is a common problem in developing world. It can affect a large number of asymptomatic people in whom it may cause serious complications in long run. Moreover, these asymptomatic infected people pose a serious risk for the transmission of infection to healthy population. Objective of this study was to estimate the frequency of Hepatitis C in asymptomatic adult patients attending medical OPD of District Headquarters Hospital Kotli, Azad Kashmir, and to assess the risk factors associated with its transmission. Methods: This was a cross-sectional study that included asymptomatic patients of both genders, aged 15-80 years, attending medical OPD of District Head quarter Hospital Kotli, Azad Kashmir from January to December, 2008. They attended the OPD for problems other than Hepatitis and most of them presented with vague complaints like generalised body aches, tiredness and dyspeptic symptoms. They were randomly tested for Hepatitis C virus (HCV) antibodies by Immuno chromatographic kit method. Positive samples for Hepatitis C antibodies were confirmed by third generation ELISA. Those who were confirmed were assessed for the risk factors associated with HCV transmission. Results: The study included 9,564 patients. Out of them 4,2 (44.22%) were males and 5,334 (55.77%) were females. A total of 611 (6.38%) cases were positive for HCV; 257 (6.08%) were males, and 354 (6.64%) were females. Highest frequency (36%) was found between 21 and 30 years of age, and 60.54% positive patients were 21-40 years old. Blood transfusion was the most common (34.36%) risk factor followed by history of dental procedures (24.54%). In 27.16% no risk factor could be detected. Conclusion: Frequency of Hepatitis C is quite high in our population. Rate is higher in young adults. It is needed to adopt organised preventive strategies to overcome this problem. Blood transfusion is still the most significant risk factor followed by dental and surgical procedures. Health related procedures are still not safe in our set up and need to be addressed. (author)

[en] Genetic analysis of selected genome regions of hepatitis A virus (HAV) suggested that distinct genotypes of HAV could be found in different geographical regions. At least seven HAV genotypes have been identified all over the world, including four human genotypes (I, II, III, and VII) and three simian strains (IV, V, and VI). Phylogenetic analysis using full-length VP1 sequences revealed that human strain 9F94 has a close genetic relation with strain SLF-88 (sub-genotype VII). Nevertheless, the same analysis using full-length VP2 or VP3 sequences revealed that strain 9F94 has a close genetic relation with strain MBB (sub-genotype IB). To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossing over had taken place in the VP1 capsid protein. These findings indicate that capsid-recombination can play a significant role in shaping the genetic diversity of HAV and, as such, can have important implications for its evolution, biology, and control