Hepatitis: Wang B

Saksena NK, Wang B, Steain M, Yang RG, Zhang LQ. · Centre for Virus Research, Westmead Millennium Institute, The University of Sydney, Westmead NSW 2145 Sydney, Australia. · Cell Res. · Pubmed #16354574 links to  free full text

Abstract: Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV-1 subtypes, consequent emergence of recombinant and novel forms of HIV-1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naïve patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.

Lu Y, Wang B, Yu L, Liu C, Wu Z, Pan CE. · Department of Hepatobiliary Surgery, First Hospital of Xi'an Jiaotong University, Xi'an 710061, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #15567733 links to  free full text

Abstract: BACKGROUND: Chronic hepatitis B virus infection is one of the major causes of liver cirrhosis worldwide, especially in Asia. Liver transplantation for the end-stage liver disease with hepatitis B virus(HBV) is commonly complicated by the recurrence of HBV. The present study was designed to evaluate lamivudine in the prevention and treatment of recurrent HBV after liver transplantation. METHODS: Seventeen patients with HBV-related liver disease in a total of 41 patients have received liver transplantation at our hospital since 2001. All the patients were HBV positive before transplantation, 5 of them had acute liver failure. Artificial liver was used in 4 patients with acute liver failure. All of the patients received lamivudine at a dose of 100 mg/d after liver transplantation. Lamivudine and HBIg therapy were given to 3 patients. RESULTS: Liver transplantation was successfully performed in all 17 patients. Three patients died of complications 3-6 months after the transplantation. One patient withdraw from lamivudine therapy and died of liver failure at 14 months after the transplantation. Thirteen patients were followed up from 6 to 18 months. Two viremic patients had HBV recurrence shortly after the transplantation. Two viremic patients who had received HBIg and lamivudine after the transplantation had no evidence of HBV recurrence. CONCLUSIONS: Lamivudine therapy is effective in preventing HBV recurrence after liver transplantation. The recurrence of HBV is closely related to HBV DNA status before liver transplantation.

Yao G, Cui Z, Wang B, Yao J, Zeng M. · Clinical Immunology Centre, Jing'san Qu Central Hospital, Shanghai 200040, China. · Chin Med J (Engl). · Pubmed #12622930 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term efficacy and safety of lamivudine therapy for the treatment of chronic hepatitis B and the clinical influence of emergence of tyrosine methionine aspartic acid (YMDD) motif mutation of hepatitis B virus (HBV). METHODS: This multicenter, double-blind, randomized, placebo controlled trial began in 1996. A total of 429 patients with HBsAg, HBeAg and HBV CNA positives were enrolled. They were randomized to receive either lamivudine 100 mg daily (n = 322) or placebo (n = 107) on 3 : 1 ratio for the first 12 weeks. Thereafter all patients were offered open label lamivudine treatment and assessed every 4 weeks for a total of 104 weeks. RESULTS: After 1 year treatment 72.7% patients (285/392) had a sustained serum HBV DNA response. HBV DNA continued to be substantially suppressed at the second year, except in patients with the emergence of YMDD mutation whose mean HBV DNA levels increased to 86 Meq/ml (bDNA assay) but were much more lower than that of pre-treatment baseline level. lamivudine therapy resulted in increased HBeAg loss and HBeAg/anti-HBe seroconversion, which were correlated with both baseline alanine transaminase (ALT) levels and also with duration of lamivudine treatment. HBeAg loss was achieved in 26.8% of patients with ALT > 1-fold upper limit of normal at 2 yeas and in 35.6% and 55.6% of patients with ALT > 2-fold upper limit of normal and ALT > 5-fold upper limit of normal, respectively. For HBeAg seroconversion, these figures were 17.4%, 22.2%, and 33.3% respectively. By the end of 2 years, ALT levels were remained in normal ranges in 50.3% whose ALT were abnormal before treatment, and in 83% whose ALT were mormal before treatment. YMDD mutation were developed in 49.7% of the patients. Their serum HBV DNA levels were slightly increased to bDNA median level 86 Meq/ml and 15% of the patients they were ALT exceeded baseline levels. Four patients clinically flared-up and recovered after stop treatment. The adverse drug reactions (ADRs) of lamivudine were mild to moderate, only two patients were reported as drug related severe ADR. CONCLUSION: Sustained HBV replication and clinical improvement could be obtained by the long-term lamivudine therapy with good tolerance and safety.

Yao G, Wang B, Cui Z, Yao J, Zeng M. · Shanghai Jinganqu Central Hospital, Shanghai 200040, China. · Chin Med J (Engl). · Pubmed #11593504 No free full text.

Abstract: OBJECTIVE: To evaluate the effect of lamivudine on the loss of serum hepatitis B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo. METHODS: Four hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: During the 12-week treatment period, 92.2% of lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78.5% compared with the placebo group (11.1%; P < 0.01). There was a trend to a high proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with elevated ALT levels at baseline became normal in 60. 3% of the lamivudine treated group compared with the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well tolerated in a dose of (100 mg daily) and the overall incidence of adverse events was similar to that of the placebo. CONCLUSIONS: Lamivudine (100 mg daily) is very effective in the inhibition of HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.

Yao G, Wang B, Cui Z. · Jing'an Qu Central Hospital, Shanghai. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #10488413 No free full text.

Abstract: OBJECTIVE: To evaluate the long-term effect of lamivudine on the loss of serum HBV DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance with multi-center, randomized, double blind and placebo controlled trial. METHOD: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event. CONCLUSION: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.

Marks DH, Adineh M, Wang B, Gupta S. · Department of Medicine, Cooper Green Mercy Hospital, Birmingham, Alabama, USA. · Neuropsychiatr Dis Treat. · Pubmed #19300595 links to  free full text

Abstract: Interferon alfa2 (IFN-alpha2) is a parenterally administered cytokine used to treat patients with Hepatitis C and B, and malignancy. Interferon (INF) has a relatively high rate of central nervous system (CNS) adverse effects, including agitation, depression, fatigue, cognitive dysfunction, suicidal thought and drug craving. Using functional magnetic resonance imaging (fMRI) we studied patients with Hepatitis C virus (HCV) infection who were not more than mildly clinically depressed at baseline for their CNS reaction to IFN-alpha2. During fMRI, patients underwent visual stimulation with pictures designed to induce feelings of depression. In the two patients who became clinically depressed or markedly anxious while on treatment with interferon, but not in patients who did not experience these effects, there was a significant activation in specific areas of the brain known to be involved with depression, along with an increase above baseline in the Beck Depression Scale for the patient who developed INF-induced depression. The activation pattern differed from that previously observed for endogenous depression, indicating that INF-induced depression may differ in its underlying neuropathology. Functional magnetic resonance imaging can be an important tool in understanding and monitoring for (INF and other) medication-induced CNS effects, and response to treatment.

Wang B, Lu Y, Yu L, Liu C, Liu X, Wu Z, Zhu HT, Pan CE. · Department of Hepatobiliary Surgery, First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. · Transpl Infect Dis. · Pubmed #19210689 No free full text.

Abstract: BACKGROUND: Tuberculosis (TB) infection in a liver transplantation candidate is not rare in China. There is little experience on how to manage the pre-existing TB infection in liver transplantation recipients. Aim. Patients with pre-existing pulmonary TB who received liver transplantation are described and the perioperative treatment is discussed. METHODS: The treatment of 3 patients with pre-existing pulmonary TB infection who received liver transplantation was reviewed. RESULTS: The patients were given nonstandard antituberculous therapy according to their reaction to the drugs. No evidence of TB infection relapse was discovered. CONCLUSION: Pre-existing TB infection should not be an absolute contraindication to orthotopic liver transplantation. The use of second-line antituberculous therapy is safe and effective for the treatment of TB infection in liver transplantation recipients.

Feng Y, He F, Zhang P, Wu Q, Huang N, Tang H, Kong X, Li Y, Lu J, Chen Q, Wang B. · State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China. · Antiviral Res. · Pubmed #19150374 No free full text.

Abstract: Natural killer (NK) cells and cytolytic T lymphocytes (CTL) have been implicated as important effectors of antiviral defense. We previously isolated a novel antibacterial polypeptide, which was identified as high mobility group nucleosomal-binding domain 2 (HMGN2), from human mononuclear leukocytes. This study examined the antiviral activity of HMGN2 against human hepatitis virus B. HMGN2 was isolated and purified from the acid soluble proteins of the human THP-1 cell line, and identified by mass spectrum, Western blot and antibacterial assay. The hepatitis B virus (HBV)-transfected HepG2.2.15 cell line was used in the in vitro assay system. In the range of 1-100 microg/ml HMGN2, no cytotoxicity for HepG2.2.15 cells was detected by MTT assay. When incubated with HMGN2 at 1-100 microg/ml for 72 or 144 h, there was a significant reduction in hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) expression, which were detected by ELISA, and a significant reduction in HBV DNA copies, which was determined by the real time quantitative PCR, in the supernatant of HepG2.2.15 cells. Northern and Southern blot analysis also showed that the levels of the HBV 3.5 kb and the 2.4/2.1 kb mRNA species and HBV replicative intermediate DNA were significantly reduced in the HMGN2-treated HepG2.2.15 cells. These results indicated that HMGN2 protein could markedly inhibit HBV protein expression and replication in vitro.

Zhang XF, Meng B, Qi X, Yu L, Liu C, Liu XM, Wang B, Pan CE, Lv Y. · Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China. · Eur J Surg Oncol. · Pubmed #18835514 No free full text.

Abstract: AIMS: Little is known in judging significant factors that affect the outcome of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV)-related cirrhosis undergoing liver resection. The aim of the present study is to investigate the controllable and uncontrollable poor prognostic factors for hepatectomy in patients with HBV-related cirrhosis. METHODS: Clinical and pathological data of 412 HCC patients with HBV-related cirrhosis undergoing liver resection from October 1996 to October 2006 were retrospectively reviewed and the prognostic risk factors were analyzed by univariate and multivariate analyses. Cumulative survival was calculated with respect to the number of prognostic risk factors. RESULTS: The significant risk factors for decreasing both the overall and disease-free survival of patients were: (1) ascites volume of more than 500 ml; (2) prothrombin time of more than 4s; (3) serum AFP of more than 400 ng/ml; (4) tumor distribution in two lobes; (5) vascular invasion; (6) capsule absence; and (7) blood transfusion of more than 600 ml. Moreover, female gender and operation time of more than 5h are risk factors of tumor recurrence but not for the patients' overall survival. The 3-year survival rate decreased from 100% to 0 as the number of risk factors in the patients increased from zero to four or more. Patients who had two or more preoperative risk factors were poor candidates for liver resection, with a 3-year survival rate of 8.5%. CONCLUSIONS: The survival of HCC patients with HBV-related cirrhosis after liver resection depends on preoperative liver reserve, tumor status and blood transfusion. Tumor status cannot be altered; however, the surgeon can do a great favor to the prognosis of patients by minimizing bleeding and blood transfusion. Patients with two or more preoperative risk factors should be cautiously selected for liver resection.

Zhang XL, Zhu XF, Shi HJ, Cui SZ, Tang YQ, Ba MC, Wang JK, Wang B, Lu Q, Zhao HY, Wu YB, Li ML. · Department II of Abdominal Surgery Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #18646715 No free full text.

Abstract: OBJECTIVE: To investigate the effect of the regimen of lamivudine (LAM) combined with hepatitis B immunoglobulin (HBIG) in prevention and treatment of re-infection of hepatitis B virus (HBV) and recurrence of hepatitis B after orthotopic liver transplantation (OLT) for HBV related end stage liver disease. METHODS: The clinical data of 183 adult liver transplantation patients who lived more than 6 months and were followed up for 14.6 months with complete data were studied retrospectively. According to the HBV prevention strategy, these recipients were divided into two groups: group of pure LAM (n = 106) and group of LAM plus intramuscular injection of low dose HBIG (n = 77). RESULTS: The rate of HBsAg negative conversion 1 week after OLT of the LAM group was 82.10% (87/106), significantly lower than that of the LAM + HBIG group [94.81% (73/77), P = 0.010]. The rates of HBV reinfection, HB recurrence, and YMDD mutation of the lamivudine group were 16.98% (18/106), 11.32% (12/106), and 8.49% (9/106) respectively, all significantly higher than those of the LAM + HBIG group [6.49% (5/77), 2.60% (2/77), and 1.30% (1/77) respectively, P = 0.035, 0.028, and 0.035 respectively]. All the patients with YMDD mutation were treated with adefovir (ADF) with improvement. Analysis showed no obvious difference in the effect of LAM given intramuscularly or intravenously. CONCLUSION: The protocol of combination of LAM and HBIG is highly effective, safe, and cost-effective in preventing the recurrence of HBV after OLT. YMDD mutation can be treated by ADF with satisfactory results.

Zhang XF, Lv Y, Xue WJ, Wang B, Liu C, Tian PX, Yu L, Chen XY, Liu XM. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, People's Republic of China. · Transplant Proc. · Pubmed #18589112 No free full text.

Abstract: OBJECTIVE: We sought to explore the prevalence, clinical manifestations, diagnostic procedures, and treatment of tuberculosis (TB) after solid organ transplantation. PATIENTS AND METHODS: In this study, we retrospectively analyzed data of 1947 renal transplant recipients and 85 liver transplant recipients. RESULTS: TB developed in 28 organ transplant recipients with a prevalence of 1.38% (28/2032). The median interval between transplantation and development of TB was 32 months (range, 1-142 months). Mycobacterium tuberculosis isolation, histologic signs of caseating granulomas, and TB-DNA detection directly supported the diagnosis in 10 (35.71%), 7 (25.00%), and 5 (17.86%) patients, respectively. In addition, 6 patients (21.43%) highly suspected of TB infection received tentative antituberculosis treatment with favorable responses. Most renal transplant recipients (22/25; 78.57%) received isoniazid, rifampicin (or rifabutin), and ethambutal (or pyrazinamide) for a mean duration of 10 months (range, 6-14 months). Three liver transplant recipients received a different protocol: isoniazid, rifabutin, ethambutal, and ofloxacin for 3 months; then isoniazid and rifabutin for 6 months. Upon follow-up, 8 subjects (28.57%) died; 5 of the deaths were related to TB. During the antituberculosis therapy, toxic hepatitis was seen in 12 patients (42.86%); cyclosporine levels decreased in 15 patients (53.57%); and allograft rejection developed in 6 of them. CONCLUSIONS: The peak incidences of TB in liver and kidney transplantations are in the first year and after the first year posttransplantation, respectively. Response to antituberculosis treatment should be considered to make a diagnosis among patients highly suspected of TB infections. Except in special circumstances, antituberculosis treatment protocols including isoniazid and rifampicin for about 10 months seem significantly effective and tolerable for non-liver transplant patients. Fluoroquinolones should be emphasized in posttransplantation TB treatment.

Wang J, Su B, Ding Z, Du X, Wang B. · State Key Laboratories of Agro-biotechnology, College of Biological Science, China Agricultural University, Beijing 100094, China. · Biochem Biophys Res Commun. · Pubmed #18502198 No free full text.

Abstract: Cimetidine (CIM), a histamine 2-receptor antagonist, is postulated to enhance immune responses owing to its inhibitory effects on suppressor T cells. In this report, we evaluated effects of cimetidine on the potency of antigen-specific immunity generated by DNA vaccine encoding hepatitis B surface antigen (HBsAg, pcD-S2). Our data demonstrate that CIM as adjuvant significantly increased HBsAg-specific cell-mediated and humoral immunities that were characterized by higher Ig2a/IgG1 ratio. In addition, CIM significantly promotes an elevated level of IL-4 and IFN-gamma in antigen-specific CD4(+) T cells and a robust antigen-specific cytotoxic response in the animals immunized with pcD-S2 plus CIM. Further, CIM induces pro-inflammatory cytokine expression such as the IL-12 and down-regulates anti-inflammatory cytokine expression such as IL-10 and TGF-beta, which may lead to an impairment of CD4(+)CD25(+) Treg cell-mediated suppression. Collectively these findings suggest that CIM enhances the immune responses of HBV DNA vaccine through the stimulation of pro-inflammatory and inhibition of anti-inflammatory cytokine expression patterns.

Zhou YM, Yang JM, Li B, Yin ZF, Xu F, Wang B, Liu P, Li ZM. · Department of Hepato-Biliary-Pancreato-Vascular Surgery, The First Xiamen Hospital, Fujian Medical University, Xiamen, China. · World J Gastroenterol. · Pubmed #18407604 links to  free full text

Abstract: AIM: To explore clinicopathologic characteristics of intrahepatic cholangiocarcinoma (ICC) in patients with positive serum a-fetoprotein (AFP). METHODS: One hundred and thirty one patients who underwent surgical dissection for pathologically confirmed ICC were divided into a positive AFP (> 20 ng/mL) group (n = 32) and a negative AFP group (n = 99), whose clinicopathologic features were analyzed and compared. RESULTS: The positive rate of HBsAg and liver cirrhosis of the positive AFP group was higher than that of the negative AFP group, while the positive rate of CA19-9 (> 37 U/mL) and the lymph node metastasis rate was lower. CONCLUSION: ICC patients with positive AFP share many clinicopathologic similarities with hepatocellular carcinoma.

Lu Y, Wang B, Huang H, Tian Y, Bao J, Dong J, Roggendorf M, Lu M, Yang D. · Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. · Dev Comp Immunol. · Pubmed #17936902 No free full text.

Abstract: The interferon-alpha (IFN-alpha) gene family is an important part of the immune system. Recombinant interferon-alpha is widely used to treat viral hepatitis and malignant diseases. Marmota himalayana has been found to be susceptible to woodchuck hepatitis virus, a virus genetically related to hepatitis B virus (HBV), and is suitable as an animal model for studies on HBV infection. Here, the IFN-alpha gene family of M. himalayana (cwIFN-alpha) was characterized. Sequence data indicate that the cwIFN-alpha family consists of at least 8 functional sequences and 6 pseudogenes with high homology within the family and to IFN-alpha of Marmota monax, a related species and well-established animal model. The recombinant cwIFN-alpha subtypes were expressed and tested to be active in viral protection assay and to induce expression of MxA in a species-specific manner. This work provides essential information for future work on testing new therapeutic approaches of HBV infection based on IFN-alpha in M. himalayana.

Jin H, Xiao W, Xiao C, Yu Y, Kang Y, Du X, Wei X, Wang B. · State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China. · Viral Immunol. · Pubmed #17931113 No free full text.

Abstract: To display antigenic protein on the surface of virus-like particles (VLPs) presents a potentially powerful strategy for vaccine development. We genetically engineered the major capsid protein VP1 of foot-and-mouth disease virus (FMDV) into the predominant epitope C of HBV core gene to yield a chimeric core-VP1 VLP. The VLP was successfully expressed in HeLa cells transfected with core-VP1 DNA construct. Compared with a regular VP1 DNA construct, immunization with core-VP1 DNA induced significantly higher levels of antigen-specific IgG production, T cell proliferation, cytotoxic T lymphocyte response, and cytokine production in mice. Most importantly, the level of neutralizing antibody elicited by core-VP1 immunization was significantly higher than that with VP1 DNA immunization, which correlated well with animal protection level from subsequent live FMDV challenge. Thus, immunization with chimeric VLP induces higher efficacy and provides an attractive DNA vaccine strategy for controlling FMDV infection in future.

Yang Y, Huang H, Zhang Z, Wang B, Tian Y, Lu M, Yang D. · Center of Experimental Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #17828498 No free full text.

Abstract: The objective of this study is to express the carbohydrate recognition domain (CRD) of the asialoglycoprotein receptor (ASGPR) H1 and H2 subunits of Marmota himalayan in vitro, and develop polyclonal antibodies against the recombinant proteins. RT-PCR was used to amplify ASGPR CRDH1 and CRDH2 from the liver tissue of Marmota himalayan. The products of amplification were subcloned into prokaryotic expression vector pRSET-B, and expressed in E.coli BL21(DE3)plysS. The recombinant proteins were purified using Ni-NTA spin column. The purified proteins were inoculated into BALB/c mice to develop polyclonal antibodies. The sensitivity and specificity of antibodies were evaluated by enzyme-linked immunosorbent assay (ELISA), Western blotting and immunohistochemical staining (IHC). The polyclonal antibodies showed high sensitivity and specificity against both denaturated and native ASGPR proteins. We successfully amplified and expressed the ASGPR CRDs of Marmota himalayan. The nucleic sequences of ASGPR CRDH1 and CRDH2 of Marmota himalayan have been submitted to Genbank and the sequence ID are DQ 845465 and DQ845466, respectively. The proteins and antibodies prepared can be used for targeting gene therapy in a new animal model-Marmota Himalayan-for the research of infectious diseases of hepatitis viruses and liver cancer treatment.

Liu Z, Tian Y, Wang B, Yan Z, Qian D, Ding S, Song X, Bai Z, Li L. · Department of Microbiology, Key Laboratory of Medicine and Biotechnology of Qingdao, Qingdao University Medical College, Qingdao, Shandong, China. · J Med Virol. · Pubmed #17705191 No free full text.

Abstract: Human cytomegalovirus (HCMV) is a widespread pathogen, the most common congenital viral infection, and the leading cause of infant hepatitis syndrome. In this study, serum samples were collected from 20 HCMV-infected infants with hepatitis and 25 controls. Of the 25 infants in the control group, 5 were infected with HCMV but without hepatitis, 10 had hepatitis but no HCMV infection, and 10 were healthy. Proteomic expression in the serum was detected by WCX2 chips and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), to identify serum protein biomarkers in infants with hepatitis syndrome resulting from HCMV. Fifteen protein peaks were distinctly different among the four groups in the mass range from 2,000 to 20,000 Da. Of these 15 peaks, 4 at 4,349.8, 5,808.7, 7,935.6, and 8,885.9 Da were significantly different between the congenital HCMV-infected infants with hepatitis and the controls. Five peaks were distinctly up-regulated in the infants with HCMV infection (3,266.8, 5,638.5, 5,909.1, 7,771.4, and 15,835.6 Da) compared to those without HCMV infection. Two proteins at 4,600.1 and 5,704.3 were up-regulated in infants with HMCV infection but no hepatitis. Four protein peaks were markedly different (7,567.0, 13,744.8, 15,100.7, and 15,915.0 Da) between the infants with hepatitis and the other controls. Comparison of the differentially expressed proteins' properties with those available on an international database suggest that specific serum proteins such as the augmenter of liver regeneration, pre-albumin, and haptoglobin closely related to liver function, and cytokines such as beta-defensins 31 and 8, and macrophage-derived chemokine, among others, are involved in HMCV infection and the pathogenesis of HMCV-induced hepatitis in infants.

Wang K, Fan X, Fan Y, Wang B, Han L, Hou Y. · Hepatology Department, Qilu Hospital, Shandong University, Jinan, China. · J Viral Hepat. · Pubmed #17381720 No free full text.

Abstract: Hepatitis B virus (HBV) infection induces a wide range of chronic liver injury. The mechanism by which HBV evades the immune surveillance system remains obscure. Plasmacytoid dendritic cells (pDCs) seem to be the major endogenous interferon (IFN)-alpha producers and represent one of the most important cell types in the regulation of antiviral innate immunity; however, the phenotype and function of pDCs in patients infected by HBV with different genotypes are yet to be determined. The aim of this study was to investigate the differences in the numbers and function of peripheral blood pDCs in the immune clearing phase of chronic HBV infection with genotypes B and C. Fifty-six patients with persistent HBV infection were included in this study, with 19 age-matched healthy subjects being used as a control group. The frequencies of pDCs were analysed by flow cytometry, and the IFN-alpha produced by peripheral blood mononuclear cells (PBMCs) after stimulation with cytidine phosphate guanosine (CpG) oligonucleotides for 24 h was determined by enzyme-linked immunosorbent assay. The genotypes of HBV were detected by polymerase chain reaction and hybridization. The results showed that the frequency and IFN-alpha-producing capacity of peripheral blood pDCs were dramatically reduced and relatively inversely correlated with the level of serum alanine aminotransferase in both groups of patients with chronic genotype B and C HBV infection. A lower reduction of IFN-alpha production by CpG-stimulated PBMCs was found in patients with genotype C than in those with genotype B in the phase of immune clearance. In conclusion, the frequency and IFN-alpha-producing capacity of peripheral blood pDCs were dramatically reduced in the immunoactive phase of chronic hepatitis B (CHB). Furthermore, the lower reduction in IFN-alpha production in patients with genotype C than in those with genotype B may correlate with the outcome of antiviral treatment in CHB patients and the progression of liver inflammation.

Du X, Zheng G, Jin H, Kang Y, Wang J, Xiao C, Zhang S, Zhao L, Chen A, Wang B. · State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing 100094, China. · J Gene Med. · Pubmed #17310492 No free full text.

Abstract: Because DNA vaccines on their own tend to induce weak immune responses in humans, adjuvant methods are needed in order to improve their efficacy. The co-stimulatory molecules 4-1BBL, OX40L, and CD70 have been shown to induce strong T cell activities; therefore, in this study, we investigated whether they may be used as molecular adjuvants for a hepatitis B surface antigen (HBsAg) DNA vaccine (pcDS2) in eliciting strong cellular and memory responses. Compared to mice immunized with pcDS2 alone, addition of the co-stimulatory molecules increased T cell proliferation and an HBsAg-specific antibody response that was marked with a higher ratio of IgG2a/IgG1. Importantly, pcDS2 plus these co-stimulatory molecules elicited a higher level of IFN-gamma and IL-4 in CD4(+) T cells and a higher level of IFN-gamma in CD8(+) T cells. In addition, a significantly robust antigen-specific cytotoxic T lymphocyte (CTL) response and the production of long-term memory CD8(+) T cells were also observed in the groups immunized with pcDS2 plus 4-1BBL, OX40L, or CD70. Consistently, as late as 100 days after immunization, upregulated expressions of BCL-2, Spi2A, IL-7Ra, and IL-15Ra were still observed in mice immunized with pcDS2 plus these co-stimulatory molecules, suggesting the generation of memory T cells in these groups. Together, these results suggest that the co-stimulatory molecules 4-1BBL, OX40L, or CD70 can enhance the immunogenicity of HBsAg DNA vaccines, resulting in strong humoral, cellular, and memory responses. This approach may lead to an effective therapeutic vaccine for chronic hepatitis B virus (HBV) infection.

Tang KF, Wang Y, Wang P, Chen M, Chen Y, Hu HD, Hu P, Wang B, Yang W, Ren H. · Key Laboratory of Molecular Biology for Infectious Diseases of State Ministry of Education, The second Affiliated Hospital, Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, PR China. · Biochim Biophys Acta. · Pubmed #17303335 No free full text.

Abstract: It has been reported that RNAi-dependent chromatin silencing in vertebrates is not restricted to the centromeres. To address whether RNAi machinery could regulate the chromatin structure of imprinted genes, we knocked down Dicer in HEK293 cells and found that the expression of PHLDA2, one of the several genes in the imprinted gene domain of 11p15.5, was specifically upregulated. This was accompanied by a shift towards more activated chromatin at PHLDA2 locus as indicated by change in H3K9 acetylation, however, the methylation state at this locus was not affected. Furthermore, we found that PHLDA2 was downregulated in growth-arrested HEK293 cells induced by either serum deprivation or contact inhibition. This suggests that PHLDA2 upregulation might be a direct result of Dicer depletion rather than the consequence of growth arrest induced by Dicer knockdown. Considering the reports that there is consistent placental outgrowth in PHLDA2 knockout mice and that PHLDA2 overexpression in mice causes growth inhibition, we speculate that PHLDA2 may be a candidate for contributing to the reduced growth rate of Dicer-deficient cells and the very early embryonic lethality in Dicer knockout mice.

Han J, Ye M, Xu M, Sun J, Wang B, Guo D. · The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100083, China. · J Chromatogr B Analyt Technol Biomed Life Sci. · Pubmed #17118721 No free full text.

Abstract: The root of Scutellaria baicalensis, called Huangqin in Chinese, is one of the most commonly used traditional Chinese medicines for the treatment of hepatitis, tumors, diarrhea, and inflammatory diseases. The major chemical constituents of Huangqin are flavonoids. In the present paper, HPLC-DAD-ESI-MS(n) was used to analyze flavonoids in the roots of S. baicalensis. A total of 26 flavonoids were identified or tentatively characterized, including 5 C-glycosides, 12 O-glycosides, and 9 free aglycones. Two C-glycosides, apigenin-6-C-glucyl-8-C-arabinoside and chrysin-6,8-di-C-glucoside, together with some O-glycosides, are reported from S. baicalensis for the first time. This method is simple, reliable and sensitive, and could be used for the quality control of Huangqin and its related preparations.

Wang K, Chen LY, Wang B, Han LY, Hou YD. · Department of Liver Disease of Qilu Hospital, Shandong University, Jinan 250012, China. Corresponding author: WANG Kai, E-mail: · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #17086285 No free full text.

Abstract: BACKGROUND: The aim of this study was to access phenotype changes of dendritic cells (DC) cultured from peripheral blood mononuclear cells (PBMC) in patients with chronic hepatitis B and to reveal the relationship between phenotype of DC and ALT or HBV DNA. METHODS: Indices of ALT and serum HBV DNA were measured in 37 patients with chronic hepatitis B and 21 healthy controls. Peripheral blood mononuclear cells were isolated from all patients and healthy controls, and cultured with granulocyte-macrophage colony-stumilating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor- (TNF-)in RPMI 1640 medium that contained 10% fetal calf serum. After culturing for 7 days, the DC was counted and the phenotypes were detected by FACS. Then the data were statistically analysed. RESULTS: The DC was significantly fewer (P less than 0.05) in patients with chronic hepatitis B than the controls. In particular, the expressive level of CD83 and CD86 on DC's surface from patients with chronic hepatitis B were also significantly lower (P less than 0.05) than that from the controls. In the patients with hepatitis B, the indices of DC had a significantly negative correlation with the level of serum HBV DNA (P less than 0.05), but no significant relationship was found between ALT and indices of DC (P greater than 0.05). CONCLUSION: The DC cultured from patients with chronic hepatitis B were few and had immature phenotype. These changes had a significantly negative correlation with the level of serum HBV DNA, but had not correlation with the inflammatory reaction levels in the liver. DC was associated with the clearance of HBV in patients with hepatitis B.

Liu RH, Liu HL, Wang B, Liang H, Gong XC, Li HN. · Second Department of Internal Medicine, Qingdao Medical Center for Women and Children, Qingdao 266011, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #16556430 No free full text.

This publication has no abstract.

Hong X, Yu RB, Sun NX, Wang B, Xu YC, Wu GL. · Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. · World J Gastroenterol. · Pubmed #16437632 links to  free full text

Abstract: AIM: To assess the associations of human leukocyte antigen (HLA) class II DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date. METHODS: To clarify the impact of HLA class II polymorphisms on viral clearance, we performed a meta-analysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS: Meta-analyses yielded summary estimates-odds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001] and 2.02 [95%CI (1.56, 2.62), P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION: These results support the hypothesis that specific HLA class II alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4(+)T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and well-designed studies are needed to determine the host genetic determinants of HCV infection.

Wang B, Lohrengel B, Lu Y, Meng Z, Xu Y, Yang D, Roggendorf M, Lu M. · Institut für Virologie, Universitätsklinikum Essen, Hufeland Str. 55, 45122 Essen, Germany. · Cytokine. · Pubmed #16406557 No free full text.

Abstract: Interleukin 15 (IL-15) is a member of the four-helix bundle cytokine family and has T cell growth factor activity. IL-15 plays a unique role in both innate and adaptive immune cell homeostasis, particularly for the development of NK cells and CD8+memory cells. It may be useful for stimulation of specific immune responses in chronic viral infection such as hepatitis B virus infection. The woodchuck model is an informative animal model for studies on hepadnavirus infection and therapeutic interventions. Here, the complete coding sequence of woodchuck IL-15 (wIL-15) was cloned and sequenced. wIL-15 shows a high homology (>70%) to its counterparts of other mammalian species. His-tagged recombinant wIL-15 protein was expressed and purified and showed the ability to promote the proliferation of activated mouse splenocytes and woodchuck peripheral blood lymphocytes. Further, examination of mRNA amounts in liver samples of woodchucks by semi-quantitative RT-PCR showed a slightly increased expression of wIL-15 in woodchuck livers during chronic woodchuck hepatitis virus infection. This available information will provide a basis for further studies on the function of IL-15 in the context of acute and chronic hepadnavirus infection and its potential therapeutic use for chronic hepatitis B virus infection in the woodchuck model.