The Chongqing Key Laboratory for Research of Infectious Diseases

The Chongqing, China

The Chongqing Key Laboratory for Research of Infectious Diseases

The Chongqing, China
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He D.,Chongqing Medical University | He D.,The 88th Hospital of Chinese PLA | He D.,The Chongqing Key Laboratory for Research of Infectious Diseases | Tao S.,Chongqing Medical University | And 18 more authors.
Liver International | Year: 2015

Background & Aims: The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection. Methods: In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis. Results: A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P < 0.0001), rs2856718 (OR = 0.60, P = 4e-04), rs9277535 (OR = 0.54, P < 0.0001) and rs7453920 (OR = 0.43, P < 0.0001). A synergistic relationship was seen between rs9277535 and rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10). Conclusions: TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection. © 2015 John Wiley & Sons A/S.


Wu Q.,Chongqing Medical University | Wu Q.,The Chongqing Key Laboratory for Research of Infectious Diseases | Wu Q.,General Hospital of Guangzhou Military Command | Xu C.,Chongqing Medical University | And 13 more authors.
Journal of Medical Virology | Year: 2016

Evolution patterns of HBV QS between genotype B and C during vertical transmission are not well understood. In this study, we enrolled 10 HBV infected mother-infant pairs (four pairs with genotype B, four pairs with genotype C, and two with co-infection) without anti-viral therapy. Serum HBV DNA of mothers and infants were sequenced, HBV QS complexity and diversity were analyzed, polymorphisms and mutation sites were recorded, and phylogenetic trees were performed. Our result showed that the QS complexities in P (amino acid), C/PreC (amino acid), and PreS1 (nucleotide) gene were significantly higher in mothers than in infants in pairs with genotype C (P<0.05), however, full-length and other genes showed non-significant differences (P>0.05). Unlike genotype C, QS complexity of P gene (nucleotide) was significantly higher in infants than in mothers (P<0.05) in pairs with genotype B, similarly, QS complexities of full-length and other genes (except Pre S2) were also higher in infants than in mothers but without significant differences (P>0.05). QS diversities of full-length and most genes in genotype B were comparable between mothers and their infants (P>0.05), in pairs with genotype C, dS of P, X, RT genes, genetic distance of Pre S1 gene (amino acid) and dN of Pre S1 gene were significant higher in mothers than in infants (P<0.05). Several HBV mutations correlated with immune escape, e antigen loss and drug resistance were observed in infants. The results indicated that differences of HBV QS evolution patterns between genotype B and C during vertical transmission might contribute to distinct prognosis. © 2015 Wiley Periodicals, Inc.


Tan Z.,University of the Southwest | Tan Z.,The Chongqing Key Laboratory for Research of Infectious Diseases | Li M.,University of the Southwest | Li M.,The Chongqing Key Laboratory for Research of Infectious Diseases | And 13 more authors.
Journal of Clinical Virology | Year: 2014

Background: HBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection. Objectives: We explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250. IU/ml (Abbott Diagnostics). Study design: Two hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution. Results and conclusions: HBsAg (log10IU/ml) was established for immune tolerance (4.50±0.43), HBeAg-positive CHB (4.17±0.66), inactive HBV carrier (3.32±0.44), and HBeAg-negative CHB (3.23±0.40); (p=4.92×10-35). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p=0.247). The proportions of HBsAg <2000IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p=0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p=1.23×10-4) and HBeAg-positive CHB (p=0.003), but not for HBeAg-negative CHB (p=0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p=0.030), HBeAg-positive CHB (p=0.016), and inactive HBV carrier (p=0.001), but not in HBeAg-negative CHB (p=0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p=0.338) or HBeAg-negative CHB (p=0.564) were observed. For patients with HBsAg quantitation >250IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state. © 2014 Elsevier B.V.


Wu Q.,Chongqing Medical University | Wu Q.,The Chongqing Key Laboratory for Research of Infectious Diseases | Huang H.,Chongqing Medical University | Huang H.,The Chongqing Key Laboratory for Research of Infectious Diseases | And 17 more authors.
Clinical Gastroenterology and Hepatology | Year: 2015

Background & Aims: Hepatitis B virus (HBV) infection is a leading cause of liver diseases. We investigated the efficacy and safety of telbivudine in preventing transmission of HBV from hepatitis B e antigen-positive pregnant women with high viral loads to their infants in an open-label study. Methods: We performed a prospective study of 450 hepatitis B e antigen-positive pregnant women with HBV DNA levels greater than 106 IU/mL; 279 women received telbivudine (600 mg/d) during weeks 24 to 32 of gestation, and 171 women who were unwilling to take antiviral drugs participated as controls. All newborns were vaccinated with a recombinant HBV vaccine and hepatitis B immune globulin, according to a standard immunoprophylaxis procedure. Mother-to-child transmission of HBV was determined by detection of hepatitis B surface antigen and HBV DNA in the infant 6 months after birth. Results: None of the infants whose mothers were given telbivudine tested positive for of hepatitis B surface antigen at 6 months, compared with 14.7% of infants in the control group (P= 5.317× 10-8). Levels of HBV DNA also decreased among women given telbivudine; 40 of 172 (23.2%) women given telbivudine had undetectable HBV DNA levels before delivery, compared with none of the controls. A significantly higher proportion of women given telbivudine had undetectable levels of HBV DNA in cord blood (99.1%) than controls (61.5%; P= 1.195× 10-22). No severe adverse events or complications were observed in women or infants. Conclusions: Telbivudine significantly reduces vertical transmission of HBV from pregnant women to their infants; it is safe and well tolerated by women and infants. Antiretroviral Pregnancy Registry Health Care Providers ID: 26592; Government number: Natural Science Foundation of China (NSFC) 30830090, 30972598; and Third Military Medical University Key Project for Clinical Research: 2012XLC05). © 2015 AGA Institute.


PubMed | The Chongqing Key Laboratory for Research of Infectious Diseases and Hubei University for Nationalities
Type: | Journal: The West Indian medical journal | Year: 2015

Significant liver fibrosis is recognized as the key link of therapy and prognosis in patients with chronic hepatitis B infection (CHB). The present study is designed to estimate the benefits of FibroScan (FS) in diagnosing significant fibrosis in patients with CHB.Two hundred and eight consecutive CHB patients, who underwent liver biopsy, FS and laboratory tests, were recruited. The receiver operating characteristic (ROC) curves were generated to assess the performance of non-invasive models.Liver stiffness measurement (LSM) and aspartate transaminase (AST) to platelet (PLT) ratio index (APRI), but not age-platelet index (API) or AST to alanine aminotransferase (ALT) ratio (AAR), were closely correlated with significant fibrosis; area under ROC curves (AUROC) were 0.817 (p < 0.001), 0.705 (p = 0.003), 0.626 (p = 0.065) and 0.631 (p = 0.055), respectively. When combining LSM with APRI, the AUROC was 0.813, p < 0.001.FibroScan can predict the presence of significant liver fibrosis, so as to avoid liver biopsy. It seems that the combination of FS and APRI does not significantly improve the predictive ability of significant fibrosis.

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