Vertical transmission of hepatitis B virus: propositions and future directions / 中华医学杂志(英文版)

Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.

Efficacy of a new therapeutic approach as initial treatment for tuberculous pleuritis / 中国感染控制杂志

Objective To explore the therapeutic efficacy of levofloxacin combined with anti-tuberculosis drugs and thoracic catheterization for the treatment of tuberculous pleuritis.Methods Patients who were admitted to Departments of Infectious Diseases of Hanzhong Central Hospital and Ankang Central Hospital between February 2014 and August 2016 for initial treatment of tuberculous pleuritis were included in the study,they were divided into groups A,B,C and D.Group A received 2HRZE + 7HR regimen combined with conventional drainage;group B received 2HRZE+ 7HR regimen combined with thoracic catheterization;group C received 2HRZEV + 7HR regimen combined with thoracic catheterization;group D received 2HRZEV + 10HR regimen combined with thoracic catheterization.groups B,C and D received thoracic catheterization,normal saline 20mL and urokinase 100,000U were given through the drainage tube.Results A total of 172 patients with newly diagnosed tuberctlous pleurisy were received for treatment.There were 45,53,38,and 36 cases in group A,B,C,and D respectively.The total effective rate of therapy for pleural effusion in group A was lower than that in group B(64.44％ vs 90.57％,x2 =9.863,P＜ 0.05);after two month therapy,total effective rate of therapy for pleural effusion in group B was lower than that in group C (18.87％ vs 39.47％,x2 =4.716,P＜0.05);at the end of therapy,total effective rate in group C was lower than that in group D (60.53 ％ vs 83.33 ％,x2 =4.731,P＜0.05).Conclusion For initial treatment of patients with tuberculous pleuritis,2HRZEV + 10HR antituberculosis regimen combined with thoracic catheterization and urokinase infusion can significantly improve the clinical symptoms and recovery rate of tuberculous pleuritis,facilitate drainage of pleural effusion and prevent pleural thickening,adhesion and encapsulation.

Relationship between the expression of HBV mRNA in embryos and father-to-infant HBV transmission / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate father-to-infant transmission of hepatitis B virus (HBV) by detecting HBV mRNA in the IVF embryos with paternal HBV infection.</p><p><b>METHODS</b>We collected 18 discarded IVF embryos (9 cases) with paternal chronic HBV infection, and detected HBV mRNA in the embryos by single-cell RT-PCR.</p><p><b>RESULTS</b>HBV mRNA positive signals were found in 1 of the 18 embryos with paternal serum HBV positive markers (5.6%), but no specific HBV mRNA signals were observed in the 84 embryos of the negative control group. Follow-up visits revealed no significant difference between the experimental and negative control groups either in the rate of clinical pregnancy (P > 0.05) or in that of early abortion (P > 0.05). The IVF embryo with paternal HBV mRNA positive signals was successfully implanted, but early abortion occurred. HBV infection was not transmitted to progeny in either of the two groups.</p><p><b>CONCLUSION</b>The positive results of HBV mRNA indicate that HBV can get into early-cleavage embryos through sperm and replicate there, which may be the main channel of father-to-infant transmission. HBV may interfere with the development of embryos, and even result in abortion and other adverse outcomes.</p>

Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group.</p><p><b>METHODS</b>Two-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers.</p><p><b>RESULTS</b>The overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to 15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at 12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001).</p><p><b>CONCLUSION</b>Combined immunoprophylaxis is therapeutically efficacious for treating infants born to HBsAg positive mothers. Monitoring these infants' anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.</p>

Expression of COX-2 and PPARg in the livers of patients with acute on chronic HBV-related liver failure and their relationship with clinic parameters / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expressions of cyclooxygenase-2 (COX-2) and Peroxisome proliferator-activated receptor gamma (PPARg) in liver of patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) and their correlation with clinical parameters.</p><p><b>METHODS</b>35 patients with ACLF, 35 patients with HBV related chronic liver failure (CLF), 27 patients with chronic hepatitis B(CHB) and 15 normal control were enrolled to study the expressions of COX-2 and PPARg in the liver tissues by immunohistochemical staining, and to analyze the correlation of the COX-2 and PPARg levels in liver tissues with clinical parameters.</p><p><b>RESULTS</b>COX-2 was distinctly expressed in the cytoplasm of the hepatocytes, but PPARg was mostly expressed in the nuclei of the hepatocytes and also could be seen in the cytoplasm. The expressions of COX-2 in the liver of ACLF, CLF and CHB groups increased significantly as compared with NC group (z = -5.18, -4.50, -5.32, P is less than 0.01). The levels of COX-2 in ACLF livers also increased evidently as compared with CLF groups (z = -1.98, P is less than 0.05). The expression levels of PPARg in ACLF liver tissues were much higher than the other three groups, and statistical significances existed between ACLF group and the other two groups (CLF, NC groups) (z = -2.62, -4.28, P is less than 0.01). In ACLF group, the expression of COX-2 correlated with MELD score (r = 0.337, P is less than 0.05) and the expression of PPARg correlated with HBV DNA load (r = 0.348, P is less than 0.05). Clinical data showed that the levels of AST, TBil, CHOL, PT, INR, FIB and MELD score in ACLF group were significantly different from that in CLF, CHB and NC groups.</p><p><b>CONCLUSIONS</b>COX-2 expressed in liver may be a marker to reflect the degree of inflammation and injury of liver tissue. The PPARg expression of liver could be increased during chronic HBV infection and may be a protective mechanism against liver injury.</p>

Construction of a bait plasmid containing HBV PreS1 gene in a yeast two-hybrid system and evaluation of its toxicity and self-activation / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a yeast expression vector of hepatitis B virus (HBV) PreS1 gene using the Sos-recruitment system (SRS), and evaluate the effect of the expression product on the growth of the yeast cells and activation of the reporter gene.</p><p><b>METHODS</b>The coding sequence of HBV preS1 was amplified by PCR and cloned into the yeast expression plasmid pSos. The recombinant bait plasmid pSos- PreS1 was verified by sequencing before transformation into competent yeast cells. The effects of the expression product on the yeast cell growth and activation of the reporter gene were evaluated.</p><p><b>RESULTS</b>The yeast expression vector of HBV PreS1 gene was constructed successfully. The recombinant bait plasmid showed no toxic effect on yeast cdc25H cells without a self-activation of the reporter gene.</p><p><b>CONCLUSION</b>The SRS can be used to study the proteins interacting with HBV PreS1 protein and provides a means for obtaining insight into the pathogenic mechanism of HBV.</p>

Cellular localization of HCBP1 and its interaction with HCV core protein in vivo / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the interaction of hepatitis C virus (HCV) core protein with HCBP1 and observe the expression and cellular localization of HCBP1.</p><p><b>METHODS</b>The cDNA fragments encoding HCV core protein and HCBP1 were amplified by PCR and subsequently cloned into pGEM T vector, respectively. After sequence verification, the two recombined vectors were respectively subcloned into two hybrid plasmids, pM and pVP16. pM-core, pVP16- HCBP1 and the reporter vector pG5CAT were co-transfected into COS-7 cells, and the interaction between HCV core protein and HCBP1 was assayed by detecting CAT gene expression after 48 h. The expression and subcellular localization of the fusion protein in the transfected COS-7 cells were analyzed by Western blotting and fluorescence microscopy, respectively.</p><p><b>RESULTS</b>CAT-ELISA showed that the absorbance of the co-transfection group was significantly higher than that o f the negative control groups but lower than that of the positive control group. Western blotting confirmed the expression of fusion protein in the transfected COS-7 cells. Fluorescence microscopy showed that the fusion protein was distributed mainly in the cytoplasm, and in contrast, diffuse EGFP expression was detected in COS-7 cells transfected with the empty vector.</p><p><b>CONCLUSION</b>Mammalian two-hybrid assay confirms the capacity of HCBP1 to bind HCV core protein, and the expression vector for HCBP1-EGFP fusion gene has been constructed successfully and expressed in COS-7 cells.</p>

Genomic analysis of a familial clustering of chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the peripheral blood monocyte (PBMC) gene expression profile in a familial clustering of patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>cRNA prepared from PBMC in a family with 5 CHB patients and 4 normal controls was hybridized to high-density oligouncleotide arrays (HG-U133A 2.0 Human GeneChips, Affymetrix), which interrogate the expression of approximately 22,000 human ESTs. Primary image obtained from scanning was analysed with a DNT software package. Real-time PCR was employed to confirm the gene chip results.</p><p><b>RESULTS</b>55 genes out of 22,000 ESTs were identified differently. Among the 55 genes 14 showed increased expression and 41 showed decreased expression in the familial clustering CHB patients compared with those in normal controls. Most of the genes (57%) were involved in immunity, inflammation, apoptosis, signaling transduction, and cell cycle.</p><p><b>CONCLUSION</b>These results suggest that the hosts with this broad range of gene expression alterations are susceptible to hepatic B infection.</p>