Hepatitis: Wu G

Feitelson MA, Clayton MM, Reis HM, Wu G, Lu EP. · Temple University, Department of Biology, College of Science and Technology, Suite 409, BioLife Science Building, 1900 North 12th Street, Philadelphia, PA 19122, USA. · Expert Opin Pharmacother. · Pubmed #18710349 No free full text.

Abstract: BACKGROUND: Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease (CLD) and hepatocellular carcinoma. Drugs have been developed and shown to be effective against HBV replication. These treatments are often associated with the resolution of CLD. However, they are too expensive, not well tolerated, and result in the development of resistance when given as mono or salvage therapies. In addition, most of these drugs target only the virus polymerase. OBJECTIVE: To revitalize the field, drugs with other targets and combination therapies need to be developed. METHODS: Major advances in HBV and liver cancer drug development over the past decade, focusing on Phase III trials and FDA-approved compounds, are presented. RESULTS/DISCUSSION: A number of potent nucleoside/nucleotide analogs are now available for treatment, but for the long-term management of CLD, the development of combination therapies will probably be required. Development of compounds with new virus targets will enhance the utility of combination therapies. Development of compounds to host targets altered prior to or after the development of liver cancer, as demonstrated by sorafenib, need to be developed. The goal is to devise drug cocktails that will yield sustained virus responses and halt disease progression and tumor development.

Wu G, Guo SH. · Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #15059315 No free full text.

This publication has no abstract.

Ren J, He W, Zhang R, Li Z, Cao W, Yao J, Zhu F, Zhang T, Wu G. · Cancer Center, Huazhong University of Science and Technology, Wuhan, 430022, China, · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #19513612 No free full text.

Abstract: Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma (HCC) is rarely studied so far. In this study, we investigated the RASSF2A expression and its methylation status in a cohort of 45 hepatitis B virus-associated HCC tissues and their adjacent non-carcinoma tissues by using RT-PCR and MS-PCR. Promoter methylation of RASSF2A was found in 31 (68.9%) out of 45 HCC tissues and 12 (40%) out of 30 adjacent normal tissues, respectively (P<0.05). The methylation status of PASSF2A was closely associated with the loss of RASSF2A expression and elevated serum alpha-fetoprotein level, but not significantly with clinical stage, hepatic fibrosis and K-ras mutation. It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC.

Xu LF, Wang J, Xu J, Shi N, Wu G. · National Vaccine and Serum Institute, Beijing, China. · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #17971950 No free full text.

Abstract: OBJECTIVE: To establish and optimize methods to detect the immune complexes (IC) of hepatitis B virus directly. METHODS: A C1q solid phase ELISA, mouse anti-HBs MAb solid phase ELISA and the complement consumption assay were established to detect the IC and these methods were optimized. RESULTS: All the three methods were highly sensitive, specific and reproducible. The C1q used for coating tended to lose its activity easily at room temperature. Although strict requirements are needed for the raw and processed materials for complement consumption assay and the process of manipulation is complex, it can quantitatively detect IC. Comparing to the C1q solid ELISA and complement consumption assay, the mouse anti-HBs MAb solid phase ELISA has its own merits: convenience and stability. CONCLUSION: Mouse anti-HBs MAb solid phase ELISA is the best way to detect IC directly.

Wen T, Chen Z, Yan L, Li B, Zeng Y, Wu G, Zheng G. · General Surgery Department, West China Hospital, West China Medical School of Sichuan University, Chengdu, Sichuan Province, China. · Hepatol Res. · Pubmed #17441807 No free full text.

Abstract: Aim: To evaluate the safety of remnant liver in cirrhotic patients who had undergone irregular hepatectomy with continuous normothermic hemihepatic vascular inflow occlusion for over 60 min. Methods: A group of 133 cirrhotic patients who had hepatitis B virus accompanied by hepatocellular carcinoma and had undergone irregular hepatectomy by hemihepatic vascular inflow occlusion was studied. According to the time of hemihepatic vascular inflow occlusion, patients were assigned either to the control group, treatment(60) group, or treatment(90) group. The quantity of blood loss and blood transfusion, routine liver biochemistry and postoperative complications were retrospectively analyzed. Results: The data showed that there were no significant differences in postoperative complications between the three groups. Compared to the preoperative day, the levels of aspartate transaminase (AST), alanine transaminase (ALT), prothrombin time (PT) and serum bilirubin on postoperative days 1 and 3 were significantly increased in all three groups and the levels of albumin and platelet were significantly decreased on postoperative day 1. Duration of hospital stay and the levels of ALT and AST on postoperative days 1, 3 and 7 were higher in the treatment(90) group than in the control group and treatment(60) group (P < 0.05). However, no significant differences were displayed in the length of hospital stay and the levels of AST, ALT, PT, albumin, platelet count and serum bilirubin on postoperative days 1, 3 and 7 between the control group and the treatment(60) group (P > 0.05). Conclusion: Hemihepatic vascular inflow occlusion over 60 min is a possible method for irregular hepatectomy in patients with cirrhosis caused by the hepatitis B virus. However, caution must be exercised in utilizing this method where the time of vascular occlusion is over 90 min.

Shi XF, Guo SH, Wu G, Mao Q, Yu YS, Wang JK, Zhang L, Wang ZY, Zhang XQ, Zhang QH, Zhao YR, Zeng WQ. · Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #15670485 No free full text.

Abstract: OBJECTIVES: To evaluate the effectiveness and safety of N-acetylcysteine (NAC) in treating chronic hepatitis B patients. METHODS: 144 patients with chronic hepatitis B (total bilirubin, TBil>170 mmol/L) from several centers were chosen for a randomized and double blind clinical trial. The patients were divided into a NAC group and a placebo group and all of them were treated with an injection containing the same standardized therapeutic drugs. A daily dose of 8 microgram NAC was added to the injection of the NAC group. The trial lasted 45 days. Hepatic function and other biochemistry parameters were checked at the experimental day 0 and days 15, 30, 45. RESULTS: Each group consisted of 72 patients of similar demology and disease characteristics. During the trial, 28 cases of the 144 patients dropped out. In the NAC group, at day 0 and day 30, the TBil were 401.7 vs. 149.2 and 160.1+/-160.6. In the placebo group, the TBil on the corresponding days were 384.1+/-134.0 and 216.3+/-199.9. Its decrease in the NAC group was 62% and 42% in the placebo group. At day 0 and day 45 of treatment, the effective PTa increase rate was 72% in the NAC group and 54% in the placebo group. The total effective rate (TBil + PTa) was 90% in the NAC group and 69% in the placebo group. The parameters of the two groups showed a remarkable difference. The rate of side effects was 14% in the NAC and 5% in the placebo groups. CONCLUSION: NAC can decrease the level of serum TBil, increase the PTa and reduce the time of hospitalization. NAC showed no serious adverse effects during the period of our treatment. We find that NCA is effective and secure in treating chronic hepatitis B patients.

Yan G, Huang AL, Tang N, Zhang BQ, Pu D, Xianh MQ, Lan YH, Wu G. · Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #14697128 No free full text.

Abstract: OBJECTIVE: To construct the plasmid containing short hairpin RNA (shRNA) of survivin in order to suppress the expression of survivin gene in HepG2 and SMMC-7721. METHODS: Two 20 to 21 bp reverse repeated motifs of survivin target sequence with 4 bp or 8 bp spacer were synthesized respectively and inserted into plasmid pTZU6+1 to generate the plasmid pshRNA-survivin1 and pshRNA-survivin2; plasmid pEGFP-C1-survivin and pshRNA-survivin1 or pshRNA-survivin2 plasmid were cotransfected into liver cancer cell HepG2 and SMMC-7721 to detect effect of GFP expression respectively and analyze the inhibition of survivin gene. RESULTS: The recombinant plasmid pshRNA-survivin1 and pshRNA-survivin2 were successfully constructed. The recombinant plasmids suppress the survivin expression by 80% in HepG2 and SMMC-7721. CONCLUSION: The result showed that the short hairpin RNA of survivin can efficiently suppress it's expression in HepG2 and SMMC-7721.

Sun D, Hu D, Wu G, Hu X, Li J, Fan G. · Institute of Hepatology, Beijing Army General Hospital, Beijing 100700, China. · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #12196831 No free full text.

Abstract: BACKGROUND: To explore the possibility of using retrovirus vector to carry HBV vector, and to prove that replication defective HBV could be normally packaged. METHODS: Two kinds of full length of mutant HBV gene, which express dominant negative mutants, were inserted into retrovirus vector. After recombinant retroviruses were harvested, they were used to infect Hep G2 and 2.2.15 cell line. Then the expression of HBV core antigen in the Hep G2 cell was examined by immune fluorescence, and the existence of recombinant HB virion in the culture medium was examined by PCR. RESULTS: High titer of recombinant retroviruses were obtained in the culture medium of transfected PA317 cell line. Core antigen was detectable in the recombinant retrovirus infected Hep G2 cell. Recombinant HB virion was detectable in the culture medium of recombinant retrovirus infected 2.2.15 cell. CONCLUSIONS: The results suggested that recombinant retrovirus could carry HBV vector and express HBV products. When structural protein is offered by wt-HBV, the recombinant retrovirus may function as HBV vector, therefore it could be used in anti?HBV gene therapy.

Wu G, Zhou W, Zhao Y, Guo S, Wang Z, Zou S, Zhang Q, Ren H, Huang A, Zhang D. · Institute for Viral Hepatitis of Chongqing University of Medical Sciences, Chongqing 400010, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #11856503 No free full text.

Abstract: OBJECTIVE: By clarifying the natural history of chronic hepatitis B, to evaluate its long-term therapeutic outcome, antiviral drugs efficacy and economic significance. METHODS: A cohort of 183 (mean age of 31.75?.03 years, male/female ratio: 152:31) chronic hepatitis B patients with biopsy-proven and 247 cases of general population as control were followed up by retrospective cohort study. The follow-up time was 11.81?.08 years. This study was focused on long-term clinical outcome including the rate of liver cirrhosis, hepatocellular carcinoma and death, the long-term effect of antiviral drugs and prognostic factors. RESULTS: In chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) hepatocellular carcinoma, and 20 (10.93%) died. The cumulative survival probabilities were 97.27%, 91.62%, and 84.47% in 5, 10, and 15 years, respectively. The cumulative probabilities of HCC were 0.00%, 3.19%, and 11.56% in 5, 10, and 15 years, respectively. In 247 control subjects, 6 (2.43%) died, none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in hepatitis B patients were markedly different (P<0.005) compared with controls. The overall mortality of hepatitis B patients was 4.50 folds of the general population. Cox multiple regression analysis showed that old age, severe histological injury, and the positive HBeAg were closely related to liver cirrhosis, while old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found. CONCLUSIONS: The long-term outcome of hepatitis B is poor.

Zhang Q, Wu G, Richards E, Jia S, Zeng C. · Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101300, China. · Virol J. · Pubmed #17892576 links to  free full text

Abstract: BACKGROUND: The highly heterogenic characteristic of viruses is the major obstacle to efficient DNA amplification. Taking advantage of the large number of virus DNA sequences in public databases to select conserved sites for primer design is an optimal way to tackle the difficulties in virus genome amplification. RESULTS: Here we use hepatitis B virus as an example to introduce a simple and efficient way for virus primer design. Based on the alignment of HBV sequences in public databases and a program BxB in Perl script, our method selected several optimal sites for HBV primer design. Polymerase chain reaction showed that compared with the success rate of the most popular primers for whole genome amplification of HBV, one set of primers for full length genome amplification and four sets of walking primers showed significant improvement. These newly designed primers are suitable for most subtypes of HBV. CONCLUSION: Researchers can extend the method described here to design universal or subtype specific primers for various types of viruses. The BxB program based on multiple sequence alignment not only can be used as a separate tool but also can be integrated in any open source primer design software to select conserved regions for primer design.