Hepatitis: Wu C

Zhou YH, Wu C, Zhuang H. · Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China. · Chin Med J (Engl). · Pubmed #19187625 links to  free full text

Abstract: OBJECTIVE: To review the implementation of mass vaccination of hepatitis B vaccine and its critical role in prevention of hepatitis B virus infection in China. DATA SOURCES: The data were mainly from PubMed, China Hospital Knowledge Database, and other popular Chinese journals published from 1980 to 2008. The search term was "hepatitis B vaccine". STUDY SELECTION: Original studies conducted in China and critical reviews authored by principal investigators in the field of hepatology in China were selected. RESULTS: Chinese investigators started to develop hepatitis B vaccine in late 1970s. The first home-made plasma-derived vaccine became available in 1986, which has been completely replaced by the domestically produced recombinant (yeast or Chinese hamster ovary cell) vaccine since 2001. China health authority recommended vaccinating all infants in 1992. From then on, China has put tremendous efforts in implementation of mass vaccination. The overall coverage of hepatitis B vaccine in infants has increased steadily and reached more than 95.0% in urban and 83.0% - 97.0% in rural areas. The chronic HBV carrier rate in children < 10 years of age decreased from 10.0% before the mass vaccination to 1.0% - 2.0% in 2006, and that in general population decreased from 10.0% to 7.2%; overall, the nationwide mass hepatitis B vaccination has reduced more than 30 million of chronic HBV infections and HBV related severe sequlae. CONCLUSION: The Chinese successful experience in control of hepatitis B by mass vaccination offers an example for any unindustrialized country whoever is committed to control this disease.

Qin H, Li H, Xing M, Wu C, Li G, Song J. · Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #16850751 No free full text.

Abstract: The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D, the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

Wu C, Liu Y, Zhao Q, Chen GM, Chen JH, Yan XM, Zhou YH, Huang ZH. · Department of Infectious Diseases, Drum Tower Clinical College of Nanjing Medical University, Nanjing 210008, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #19489277 No free full text.

Abstract: OBJECTIVE: To develop a method for long-term culture of human B cells from peripheral blood mononuclear cells (PBMCs) by means of human soluble CD40 ligand (sCD40L), and to investigate the proliferation and antigen-presenting function of the CD40-activated B cells. METHOD: Peripheral blood sample of 30 ml was collected from a healthy person. PBMCs were isolated and cultured in the presence of sCD40L. Flow cytometry was used to examine the proliferation, DNA cycle, and cell surface markers: CD86, CD80, major histocompatibility complex (MHC) class II, and MHC Class I of the B cells. The cells cultured for 45 days were divided into 2 groups: Group 1 incubated with the fluorescein isothiocyanate (FITC)-conjugated hepatitis-B core antigen (HBcAg-FITC) and Group 2 used as control group. Eighteen hours later cytometry and fluorescence microscopy were used to detect the peptide pulsing. RESULTS: The B cells could be cultured up to 50 days in the sCD40L culture system. The ratio of B cells in the PBMCs was 8.21% at the beginning, and increased to 70.67% by day 47, and the B cell absolute count was 6.56 x 10(5) at the beginning and increased to 8.61 x 10(6) at day 50, about 10 times higher. sCD40L promoted a strong up-regulation of cell surface markers. The expression rates of CD80, CD86, MHC-II, and MHC-I of the sCD40L-activated B cells were 83.97%, 84.73%, 99.59%, and 98.70% respectively. Flow cytometry showed that 98.10% of the B cells co-incubated with HBcAg-FITC were loaded with HBcAg. Fluorescence microscopy showed that the HBcAg was in the cytoplasm of the B cells. CONCLUSION: A human sCD40L culture system has been developed with the ability to culture human peripheral blood B cells, thus realizing the long-term proliferation and activation of human peripheral blood B cells that function as antigen-presenting cells.

Chen L, Wu C, Fan X, Gao J, Yin H, Wang T, Wu J, Wen SW. · School of Public Health, Central South University, Changsha, Hunan, China. · Int J Infect Dis. · Pubmed #19036623 No free full text.

Abstract: OBJECTIVE: To examine the presence of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), and hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in renal tissues from patients with HBV-related glomerulonephritis. METHODS: Renal tissue biopsies taken from patients with HBV-related glomerulonephritis and two control groups were prepared for immunocytochemical detection of HBsAg and HBcAg. HBV cccDNA was examined using a nested PCR. RESULTS: Of the 63 HBV-related glomerulonephritis patients studied, HBsAg was present in the renal tissues of 48 (76.2%) and HBcAg in the renal tissues of 27 (42.9%). The HBsAg and HBcAg positive rates in HBV-related glomerulonephritis patients were higher than those of the 20 patients with non-HBV-related glomerulonephritis (p<0.05). However, there was no significant difference when the HBV-related glomerulonephritis patients were compared with 12 patients with renal tuberculosis, renal atrophy, renal calculus, and renal tumor with positive serum HBV markers. In patients with HBV-related glomerulonephritis, there was no significant difference in HBsAg and HBcAg positive rates in renal tissue between patients with and without serum hepatitis B e antigen (HBeAg). By nested PCR, two of five patients with HBV-related glomerulonephritis were positive for HBV cccDNA. CONCLUSION: The location and replication of HBV in renal tissue make the kidney a potential reservoir for HBV. HBV cccDNA may be key in the search for anti-HBV drugs.

Wu C, Wang Z, Liu L, Zhao P, Wang W, Yao D, Shi B, Lu J, Liao P, Yang Y, Zhu L. · Department of Gastroenterology, Changzheng Hospital, Shanghai 200003, China. · J Gastroenterol Hepatol. · Pubmed #18823443 No free full text.

Abstract: BACKGROUND AND AIM: To screen for serum biomarkers of HBV-related hepatocellular carcinoma (HCC) and HBV-related liver cirrhosis (LC) in an attempt to seek a new method for differential diagnosis of HCC and LC using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) techniques. METHODS: Using SELDI-TOF-MS, serum proteins/peptide profiles on the immobilized metal ion affinity capture (IMAC) protein chips were obtained from 29 HCC patients and 30 LC patients. Discriminant analysis was carried out to establish new diagnostic methods using protein/peptide peaks with or without alpha-fetoprotein (AFP). RESULTS: Forty-five protein/peptide peaks changed much more in the HCC group than they did in the LC group. Discriminant analysis using the Wilcoxon rank-sum test showed high sensitivity and specificity in distinguishing HCC from LC. The most significantly differentiating peak, 3892, offered 69.0% sensitivity, 83.3% specificity and 80% positive predictive value in distinguishing HCC and LC. Interestingly, six HCC patients with negative serum AFP were confirmed by peak 3892. The combination of multi-protein peaks (m/z = 9297, 29 941) with AFP offered an 82.8% sensitivity, 93.3% specificity and 92.3% positive predictive value, which was much better than AFP alone (P = 0.013). CONCLUSIONS: Special proteins/peptides of serum may differentiate HBV-related HCC and HBV-related LC, indicating that SELDI-TOF-MS may be useful to distinguish HCC from LC with the proper discriminant analytical method. SELDI peak 3892 may be a complementary diagnostic marker to positive AFP for HCC and a potential marker for the diagnosis of AFP-negative HCC as well.

Jiang J, Zhang X, Wu C, Qin X, Luo G, Deng H, Lu M, Xu B, Li M, Ji M, Xu N. · Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou 213003, PR China. · Lipids Health Dis. · Pubmed #18652652 links to  free full text

Abstract: OBJECTIVE: To determine plasma apolipoprotein M (apoM) levels and other lipid profiles in hepatocellular carcinoma (HCC) patients compared to other chronic liver diseases and normal subjects. MATERIALS AND METHODS: 36 HCC, 68 chronic hepatitis, 29 liver cirrhosis patients and 64 normal controls were subjected in the present study. Serum lipids, lipoproteins, apolipoprotein AI (apoAI) and apoB were determined by the conventional methods. Plasma apoM levels were semi-quantitatively determined by both dot-blotting and western blotting analysis. RESULTS: Serum levels of triglycerides (TG), HDL-cholesterol, apoAI and lipoprotein (a) (Lp(a)) were significantly lower in the HCC patients than in the normal subjects, whereas there were no obvious differences on serum total cholesterol, LDL-cholesterol and apoB between HCC patients and normal subjects. However, plasma apoM levels in HCC patients were significantly increased than those in the normal subjects, but lower than those in the chronic hepatitis and cirrhosis patients. CONCLUSION: It is concluded that serum TG, apoAI, HDL-C and Lp(a) were significantly decreased in HCC patients than in controls, whereas plasma apoM levels were significantly increased in the HCC patients. Decreased serum TG, apoAI, HDL-C and Lp(a) may reflect the liver damage in HCC patients, whereas the clinical significance of increased plasma apoM levels in relation to HCC is not clear.

Deng XZ, Jiang CM, Xu K, Wang ZC, Ding WL, Yu RB, Wang J, Wu C, Zhang Y. · Medicial Institute of Nanjing Amry, Nanjing 210002, China. · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #18396669 No free full text.

Abstract: OBJECTIVE: To assess the prevalence of serum anti-F in patients with hepatitis C virus (HCV) infection and the distribution of anti-F. METHODS: The recombinant protein (HCV-F/GST) was coated onto micro titer plates as antigen. Sera of 120 patients with hepatitis C virus infection, 15 patients with hepatitis B, 3 patients with hepatitis E and 10 normal sera were tested by indirect ELISA for detecting anti-F. RESULTS: 82 samples out of the 120 (68%) HCV infected patients exhibited a positive anti-F reaction, showing significant difference from the controls with no HCV infection (P < 0.01). Data from logistic analysis showed that the positive rate of anti-F was higher in patients over 50 year olds (OR = 6.675, 95% CI: 2.407-19.071). Patients of midrange, severe phase and hepatic cirrhosis had higher rate than the others (OR = 2.749, 95% CI: 1.470-5.141). CONCLUSION: Prevalence and distribution of anti-F in Yixing hepatitis C patients was reported and which might be related to the progression of HCV infection.

Chu CL, Deng XZ, Zhang Y, Dong LL, Wang ZC, Yu RB, Wu C. · School of Basic Medicine, Nanjing Medical University, Center of Disease Prevention and Control, Nanjing Command, Nanjing 210029, China. · Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. · Pubmed #18394341 No free full text.

Abstract: AIM: To investigate the diversity of proteins' pattern of the peripheral blood mononuclear cells (PBMCs) in patients with hepatitis C virus (HCV) infection, identify the differentially expressed proteins and analyze their roles in the mechanism of chronic hepatitis C. METHODS: The total proteins from PBMCs in HCV infected patients (28) and healthy persons (10) were separated by the immobilized pH gradientjbased 2-DE. The differentially expressed proteins were screened by PDQuest analysis software, and then identified by peptide mass fingerprint (PMF) based on matrixjassisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: 2-DE results showed that the mean number of protein spots in HCV infected patients and healthy persons was 625 and 614.Twelve differential proteins were tested by MALDI-TOF-MS, and 10 of them were identified. Some of the proteins participated in protein synthesis and degradation, signal transduction, metabolism, or cytoskeleton construction while some of them were proteins of virus. CONCLUSION: 2-DE pattern of PBMCs from HCV infected patients or healthy persons has been established and ten differentially expressed proteins has been characterized. Our study is helpful for clinical detection of HCV infection and further research into the mechanisms of chronic hepatitis C.

Zhu T, Ding XP, Wan YM, Liu LX, Peng H, Huang XG, Feng YM, Wu C, Ruan YH, Han LF, Xing H, Wang JJ, Su B, Xu C, Xu JQ, Shao YM. · National Center for AIDS/STD Control and Prevention, China CDC, Beijing 100050, China. · Bing Du Xue Bao. · Pubmed #18320817 No free full text.

Abstract: Several research groups have recently reported that persistent GB virus C (GBV-C) co-infected with human immunodeficiency virus (HIV) leads to slower AIDSs disease progression than HIV-1 infection alone. However, these findings were not confirmed by several other studies. To investigate the association between GBV-C replication and plasma HIV loads and CD4+ T cell counts, 203 HIV-1 positive former blood/plasma donors(FBDs) were enrolled from Fuyang city of Anhui Province in China. Plasma specimens were collected from them and were tested for GBV-C using RT-PCR and ELISA. Out of 203 specimens, 52 (25.6%) cases were positive for GBV-C, including 35 male (67.3%) and 17 female (32.7%) cases. No significant association was identified between GBV-C infection and CD4+ T-cell counts or between GBV-C infection and HIV viral loads. Since all the subjects studied were naive to ART, the influence of therapy on AIDS disease progression was ruled out in this study. Overall, our data indicated that HIV-1 positive male FBDs were prone to be infected, GBV-C coinfection with HIV-1 does not significantly influence HIV/AIDS disease progression during the late stage of chronic HIV-1 infection.

Shen E, Li L, Li L, Feng L, Lu L, Yao Z, Lin H, Wu C. · Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. · Cell Mol Immunol. · Pubmed #17484805 links to  free full text

Abstract: An adjuvant is usually used to enhance the immune response induced by vaccines. The choice of adjuvant or immune enhancer determines the effectiveness of the immune response. Currently, aluminium (Alum, a generic term for salts of aluminium) is the only FDA-approved adjuvant. Alum predominantly induces the differentiation of Th2 cells and thus mediates an antibody immune response. Therefore, there is an urgent need for new adjuvants that enhance not only humoral but also cellular immune responses. In the present study, we demonstrates that PIKA (a stabilized dsRNA) as an adjuvant directly induces the activation and the proliferation of both B and NK cells in vitro. Injection of PIKA into mice results in the production of cytokines in vivo. In addition, the study demonstrates that PIKA promotes the maturation of bone marrow-derived dendritic cells (BMDCs) including up-regulation of the co-stimulatory molecules CD80, CD86 and CD40, and the induction of cytokines such as IL-12p70, IL-12p40 and IL-6. Importantly, after immunization of mice with HBsAg plus PIKA, the presence of PIKA enhances the titers of HBsAg-specific IgG and HBsAg-specific IFN-gamma production. These results demonstrate that PIKA as an adjuvant can promote both humoral and cellular immune responses. These might have an implication in applying PIKA as an adjuvant to be used in the design and development of both therapeutic and preventive vaccines, and used in the clinical study.

Gkretsi V, Mars WM, Bowen WC, Barua L, Yang Y, Guo L, St-Arnaud R, Dedhar S, Wu C, Michalopoulos GK. · Division of Cellular and Molecular Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. · Hepatology. · Pubmed #17385211 No free full text.

Abstract: Extracellular matrix (ECM) is fundamental for the survival of cells within a tissue. Loss of contact with the surrounding ECM often causes altered cell differentiation or cell death. Hepatocytes cultured without matrix lose patterns of hepatocyte-specific gene expression and characteristic cellular micro-architecture. However, differentiation is restored after the addition of hydrated matrix preparations to dedifferentiated hepatocytes. Integrin-linked kinase (ILK) is an important component of cell-ECM adhesions transmitting integrin signaling to the interior of the cell. ILK has been implicated in many fundamental cellular processes such as differentiation, proliferation, and survival. In this study, we investigated the role of ILK in mouse hepatocytes in vitro as well as in vivo. Depletion of ILK from primary mouse hepatocytes resulted in enhanced apoptosis. This was accompanied by increased caspase 3 activity and a significant decrease in expression of PINCH and alpha-parvin, which, along with ILK, form a stable well-characterized ternary complex at cell-ECM adhesions. The induction of apoptosis caused by ILK depletion could be substantially reversed by simultaneous overexpression of ILK, indicating that apoptosis is indeed a consequence of ILK removal. These results were further corroborated via in vivo data showing that adenoviral delivery of Cre-recombinase in ILK-floxed animals by tail vein injection resulted in acute hepatitis, with a variety of pathological findings including inflammation, fatty change, and apoptosis, abnormal mitoses, hydropic degeneration, and necrosis. CONCLUSION: Our results demonstrate the importance of ILK and integrin signaling for the survival of hepatocytes and the maintenance of normal liver function.

Wu C, Chang HG, McNutt LA, Smith PF. · Department of Epidemiology, School of Public Health, University at Albany, State University of New York, Rensselaer, NY 12144, USA. · Epidemiol Infect. · Pubmed #15724719 No free full text.

Abstract: The New York State hospital discharge database and the multiple cause-of-death file were used to estimate the mortality rate of hepatitis C in New York State excluding New York City in 1997. The mortality rate with hepatitis C was severely underestimated when each data source was used alone. Applying the capture recapture method using the hospital discharge database and the multiple cause-of-death file appears to be an efficient method to estimate the mortality rate with hepatitis C.

Kramer MG, Barajas M, Razquin N, Berraondo P, Rodrigo M, Wu C, Qian C, Fortes P, Prieto J. · Division of Hepatology and Gene Therapy, Department of Internal Medicine, School of Medicine, University of Navarra, 31008 Pamplona, Spain. · Mol Ther. · Pubmed #12668133 No free full text.

Abstract: Targeting therapeutic genes to the liver is essential to improve gene therapy protocols of hepatic diseases and of some hereditary disorders. Transcriptional targeting can be achieved using liver-specific promoters. In this study we have made chimeric constructs combining promoter and enhancer regions of the albumin, alpha 1-antitrypsin, hepatitis B virus core protein, and hemopexin genes. Tissue specificity, activity, and length of gene expression driven from these chimeric regulatory sequences have been analyzed in cultured cells from hepatic and nonhepatic origin as well as in mice livers and other organs. We have identified a collection of liver-specific promoters whose activities range from twofold to less than 1% of the CMV promoter in human hepatoma cells. We found that the best liver specificity was attained when both enhancer and promoter sequences of hepatic genes were combined. In vivo studies were performed to analyze promoter function during a period of 50 days after gene transfer to the mouse liver. We found that among the various chimeric constructs tested in this work, the alpha1-antitrypsin promoter alone or linked to the albumin or hepatitis B enhancers is the most potent in directing stable gene expression in liver cells.

Wu C, Zeng Z, Wang Q. · Department of Infectious Diseases, First Hospital, Peking University, Beijing 100034, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #11798933 No free full text.

Abstract: OBJECTIVE: To investigate the effect of retroviral vector expressing the dual--target antisense RNA of hepatitis B virus (HBV) on the replication and expression of HBV. METHODS: Recombinant retroviral vector plasmids expressing dual-target antisense RNA complementary to HBV X (1400 - 1430) and P (2375 - 2405) were constructed and transduced into 2.2.15 cells. The experimental cells were divided into PLXSN + X, PLXSN + P, PLXSN + X/P, and PLXSN + Xpos/P pos groups. The HBV expression was tested by ELISA method. HBV DNA and RNA were tested by FQ-PCR. RESULTS: The inhibition rates of 2.2.15 cells transduced with recombinant vector plasmids (PLXSN + X group, PLXSN + P group, especially the PLXSN + X/P group) on expression of HBV DNA and RNA were higher than those of blank control group, PLXSN group, and PLXSN + Xpos/Ppos group. The expression of the three ORFs, S, C, and P were significantly inhibited. CONCLUSION: The expression of HBV antisense RNA in 2.2.15 cells can inhibit the replication and expression of HBV. The inhibitory effect of dual antisense-RNA group is higher than that of single antisense-RNA group. Dual antisense RNA has the potentiality in anti-HBV gene therapy.

Wu C, Tao Q, Feng B. · Institute of Hepatology, People's Hospital, Beijing Medical University, Beijing 100044, China. · Chin Med J (Engl). · Pubmed #11593587 No free full text.

Abstract: OBJECTIVE: To induce antibody response against E2 glycoprotein derived from a Chinese genotype III/2a isolate of hepatitis C virus (HCV) in BALB/C mice by plasmid DNA-based immunization. METHODS: Plasmid p3W14 containing E2/NS1 gene derived from a Chinese genotype III/2a isolate of HCV, which was verified to express 70 kDa E2 glycoprotein in NIH3T3 cells, was used for direct intramuscular injection in BALB/C mice. Specific antibody to E2 glycoprotein was detected by recombinant E2 protein. RESULTS: Specific anti-E2 antibody could be detected in mice inoculated with p3W14(5/6). Titer of antibody ranged from 1:15 to 1:120. CONCLUSION: Successfully inducing anti-E2 antibody in mice by plasmid DNA-based immunization containing E2/NS1 gene from a Chinese genotype III/2a isolate of HCV is the first time in China.

Zhu C, Wu C, Tao Q. · Institute for Liver Disease, People's Hospital, Beijing Medical University. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #10715790 No free full text.

Abstract: OBJECTIVE: E2 glycoprotein of hepatitis C virus was expressed in mammalian cell and purified for detection of antibody against E2 in hepatitis C patients. METHODS: E2/NS1 gene derived from HCV was inserted into expression vector containing six His tag. The recombinant plasmid was transfected into mammalian cells to express E2 glycoprotein expression. E2 glycoprotein was purified by affinity chromophotography. The purified protein was used to establish EIA method for detection of antibodies against E2 in hepatitis C patients. RESULT: Expressed E2 glycoprotein was 7.0 x 10(4). Purification of the purified E2 protein was 90.2%. Twenty-nine patients were anti-E2 antibody positive(82.9%). CONCLUSION: It was the first time to establish EIA method for detection of anti-E2 antibody by purified E2 glycoprotein in China. E2 glycoprotein expressed in mammalian cells had good immunogenity and could increase the sensibility of anti-HCV detection. It suggests that E2 glycoprotein may be useful for development of new anti-HCV reagents.

Feng D, Zhou F, Wu C. · No affiliation provided · Hepatology. · Pubmed #18220305 No free full text.

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