No abstract available

[en] Th17 cells are involved in liver fibrosis by activating hepatic stellate cells (HSCs). We aimed to investigate whether HSCs are able to regulate the function of Th17 cells and to determine the relevant mechanism. Sixty-five patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. To determine the effect of HSCs on T cells, naïve CD4⁺T cells and Th17 cells were sorted from CHB patients and cultured with or without activated-HSCs, and cytokine expression and gene transcription were analyzed. In addition, the regulatory mechanism of HSCs was investigated. ELISA and qRT-PCR showed that Th17 cells from CHB patients were more pathogenic, on the basis of the expression of IL-17A, IL-23R, RORC, CCL20 and CCR6, and meanwhile, they could activate the primary HSCs. Co-culture experiments indicated that activated HSCs dramatically promoted proliferation of CD4⁺T cells in a time- and dose-dependent manner. In addition, they could induce naïve CD4⁺T cells to become Th17 cells which had a more pathogenic phenotype. Moreover, activated HSCs-mediated induction of Th17 cells might depend on the release of IL-1β and IL-6 as well as on the COX-PGE2 pathway. Th17 cells cooperated with HSCs in a proinflammatory feedback loop might provide a better understanding of the pathogenic role of Th17 cells in the chronicity of HBV infection. - Highlights: • Th17 cells from CHB patients promoted the activation of primary HSCs. • Activated HSCs induced Th17 cells which displayed a pathogenic phenotype. • The induction of Th17 cells by activated HSCs depended on IL-1β and IL-6 release as well as on the COX-PGE2 pathway.

[en] Objective: To determine the etiology of chronic liver disease in children. Study Design: Descriptive cross sectional. Place and Duration of Study: Department of Paediatrics, Combined Military Hospital Lahore, from Jun 2014 to Dec 2014. Material and Methods: This is a descriptive cross sectional study conducted at department of Paediatrics, Combined Military Hospital Lahore from 1st June 2014 to 31st December 2014. It included 150 consecutive paediatric patients (1-14 years) with chronic liver disease. Results: Out of 150 children 95 (63.33%) were male and 55 (36.66%) were females. The mean age of the children included in the study was 7.2 +- 4.6 years and the age range was 1 year to 14 years. Viral hepatitis (61, 40.67%) was the commonest cause of the liver disease followed by glycogen storage disease (11, 7.33%) and Wilson's disease in 13 (8.6%). Conclusion: There are various causes of chronic liver disease in children most common being hepatitis B and C infection. The early identification of etiology of chronic liver disease in children is of cardinal importance for optimal management of these cases.

[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] Hepatitis C virus (HCV) is efficient in the establishment of persistent infection. We have previously shown that HCV core protein inhibits T cell proliferation through its interaction with the complement receptor, gC1qR. Here we show that HCV core-induced inhibition of T cell proliferation involves a G₀/G₁ cell cycle arrest, which is reversible upon addition of anti-gC1qR antibody. Correspondingly, the expression of cyclin-dependent kinases (Cdk) 2/4 and cyclin E/D, as well as subsequent phosphorylation of retinoblastoma (pRb), is reduced in core-treated T cells in response to mitogenic stimulation. Remarkably, degradation of p27^Kip1, a negative regulator of both Cdk4/cyclin D and Cdk2/cyclin E complexes, is significantly diminished in T cells treated with HCV core upon mitogenic stimulation. These data indicate that the stability of p27^Kip1 by HCV core is associated with blocking activated T cells for the G₁ to S phase transition and inhibiting T cell proliferation

[en] The hepatitis C virus (HCV) core protein is considered to influence multiple cellular processes. We developed a human hepatoblastoma HepG2-derived inducible cell line, Hep191, which allows tightly regulated expression of the core protein at relatively low but physiological levels under control of the ecdysone-regulated promoter. By transcriptional profiling, we identified differentially expressed genes, some of which are involved in cell growth or apoptosis such as inhibitor of caspase-activated DNase (ICAD), defender against cell death 1, tumor necrosis factor (TNF) receptor 1, and cytochrome c oxidase subunit VIII. Furthermore, we found that core protein expression increases a steady-state level of ICAD protein, possibly through enhancing its promoter activity, and inhibits caspase-3 activity induced by anti-Fas antibody. Since Fas- or TNF-mediated DNA fragmentation is suppressed in the core-induced Hep191 cells, these findings suggest that expression of HCV core at physiological levels confers blocking activity of caspase-activated DNase and consequently inhibiting apoptotic cell death

[en] Hepadnaviruses including human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) express X proteins, HBx and DHBx, respectively. Both HBx and DHBx are transcriptional activators and modulate cellular signaling in in vitro assays. To test whether the DHBx protein plays a role in virus infection, we compared the in vivo infectivity and growth characteristics of a DHBV3 strain with a stop codon in the X-like ORF (DHBV3-X-K.O.) to those of the wild-type DHBV3 strain. Here we report that the two strains showed no significant difference in (i) their ability to induce infection that resulted in stable viraemia measured by serum surface antigen (DHBsAg) and DHBV DNA, and detection of viral proteins and replicative DNA intermediates in the liver; (ii) the rate of spread of infection in liver and extrahepatic sites after low-dose virus inoculation; and (iii) the ability to produce transient or persistent infection under balanced age/dose conditions designed to detect small differences between the strains. Thus, none of the infection parameters assayed were detectably affected by the X-ORF knockout mutation, raising the question whether DHBx expression plays a physiological role during in vivo infection with wild-type DHBV

[en] Hepatitis C virus (HCV) is remarkable for its ability to establish persistent infection. Studies suggest that HCV core protein modulates immune responses to viral infection and can bind Fas receptor in vitro. To further examine the role of HCV core protein in Fas signaling, full-length (aa 1-192) and truncated (aa 1-152) HCV core proteins were expressed in Jurkat lymphocytes and cells were assayed for apoptotic response, caspase activation, and Fas activation. Jurkat expressing full-length but not truncated core protein exhibited ligand-independent apoptosis. Cytoplasmic targeting of truncated core protein recapitulated its ability to induce apoptosis. Activation of caspases 8 and 3 was necessary and sufficient for full-length core to induce apoptosis. Jurkat cells expressing full-length but not truncated core protein induced Fas receptor aggregation. HCV core activates apoptotic pathways in Jurkat via Fas and requires cytoplasmic localization of core. Infection of host lymphocytes by HCV may alter apoptotic signaling and skew host responses to acute infection

[en] Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication

[en] Viral hepatitis is a major public health problem. Infection with Hepatitis C virus (HCV) leads to chronicity and there are about 170 million people infected with HCV. Up to 70% of chronically infected individuals develop active liver disease. The Objective of the study was to find out the frequency of Anti-HCV seropositivity and risk factors of Hepatitis C Virus (HCV) transmission in people of Larkana city. The study was conducted at Larkana from April 2006 to April 2007. Camps were established in the main general practitioners' clinics. A questionnaire about knowledge of HCV and risk factors of its transmission was administered to subjects. Descriptive statistics were done by SPSS-10. Total 450 cases were enrolled into this study. They were divided into 3 age groups. Eighty-nine (19.8%) cases were in age group <20 years, 262 (58.2%) were in age group 20-40 years and 99 (22.0%) were in age group >40 years. There were 353 (78.4%) male and 97 (21.6%) female subjects, out of these 450 cases 30 (6.6%) were positive for Anti-HCV. A number of risk factors of HCV transmission were present in these cases. History of therapeutic injections was present in 72 cases and 35 cases used public barber services. History of therapeutic injections and use of barber services for shave were the most frequent risk factors in our study. (author)