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Jinlin Hou,
You-Kuan Yin,
Daozhen Xu,
Deming Tan,
Junqi Niu,
Xiaqiu Zhou,
Yuming Wang,
Limin Zhu,
Yongwen He,
Hong Ren, [......],
Shanming Wu,
Yagang Chen,
Jiazhang Xu, Qinhuan Wang,
Lai Wei,
George Chao,
Barbara Fielman Constance,
George Harb,
Nathaniel A Brown,
Jidong Jia
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ABSTRACT: Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. CONCLUSION: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.
Hepatology 02/2008; 47(2):447-54. · 11.66 Impact Factor
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ABSTRACT: Oxymatrine has been shown to have a remarkable inhibitory activity to hepatitis B virus (HBV) infection with a hepatitis B virus e antigen (HBeAg) serum conversion rate of approximately 45%. In order to explore the anti-HBV mechanism of oxymatrine, the effects of oxymatrine on serum levels of T helper (h)1 cytokines (interferon (IFN)-gamma and interleukin (IL)-2) and Th2 cytokines (IL-4 and IL-10), and the expression of S gene in HBV S gene transgenic mice were studied.
Each transgenic mouse was either injected with oxymatrine or saline intraperitoneally once a day for 30 days. Serum levels of IFN-gamma, IL-2, IL-4 and IL-10 were quantitated and compared to the data before the treatment. The expression of HBV S gene in transgenic mice was analyzed at the DNA, mRNA and protein levels.
The serum levels of IFN-gamma in transgenic mice before or after oxymatrine treatment were 3.108 +/- 3.172 and 11.059 +/- 6.971 pg/mL, respectively. In contrast, serum levels before and after oxymatrine treatment for IL-4 were 29.045 +/- 13.235 and 13.024 +/- 9.002 pg/mL, respectively (P < 0.001). The serum levels of IL-2 in the control (saline injection) and oxymatrine-treated mice were 1.070 +/- 0.447 and 5.537 +/- 2.887 pg/mL, respectively (P < 0.0001); and that of IL-10 were 97.226 +/- 73.306 and 33.607 +/- 23.154 pg/mL, respectively (P < 0.01). No significant differences were observed in the expression of HBV S gene in the transgenic mice at the DNA, mRNA and protein levels before or after oxymatrine treatment.
The fact that Th1 cytokines are increased while Th2 cytokines are decreased suggests that oxymatrine treatment triggers the change of immune response to hepatitis B infection in transgenic mice, which leads to improved HBV inhibitory activities. The study can help us better understand the mechanisms of the anti-HBV drug, oxymatrine, and how it has potential as an application in clinical chronic hepatitis B treatment.
Journal of Gastroenterology and Hepatology 01/2003; 17(12):1299-306. · 2.87 Impact Factor
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ABSTRACT: To investigate the HBV quasispecies groups in the patients with chronic HBV infection.
A set of specific primers was synthesized according to DNA sequence of HBV strain found in China. The whole core promoter (CP) region was amplified by PCR method from the sera of 3 patients with chronic HBV infection, and the PCR products were subcloned into pGEM Teasy vectors. The clones were randomly selected to be sequenced. Sequence comparison of the selected clones was made to find the difference.
By comparison, it was found that each sequence of selected clones was different. The point mutation always occurred in TATA-like boxes, especially from T to C replacement on 184 site. There is a hot region (33.3% 5/15) in basic core promoter where deletion mutation frequently happened.
There is a hot deletion region near DR I in CP. The replacement at 184 nt (T to C) in the third TATA-like box may influence the expression of pre-C/C protein. The sequencing results suggest that there are HBV quasispecies groups in chronically infected patients.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 10/2002; 16(3):264-6.
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ABSTRACT: To evaluate the efficacy and safety of bicyclum, a China made new hepatocyte protecting agent, in the treatment of chronic hepatitis C (CHC).
Thirty-nine CHC patients matched demographically and clinically were randomized into two groups: bicyclum group (group A, n = 20) and placebo/bicyclum crossovergroup (group B, n = 19). Bicyclum 75mg/d or placebo was administered to these two groups respectively for 3 months. Then the patients in group A received bicyclum for further 3 months and were observed for 3 months after the treatment discontinued; and the patients in group B received bicyclum 75mg/d for six months and were observed for 3 months after the treatment discontinued. Investigation items included clinical manifestations,liver function, serum HCV RNA and anti-HCV.
In group A, the serum ALT was 120 +/- 43 U/L before treatment and was 57 +/- 32 U/L after treatment ( P < 0.01) In group B the baseline serum ALT was 126 U/L +/- 48 U/L. After the placebo administration the serum ALT was 127 U/L +/- 97 U/L (P > 0.05) and the clinical feature showed no improvement. After bicyclum treatment for 6 months, the serum ALT in group B was 68 +/- 45 U/L, significantly lower than that before bicyclum treatment ( P < 0.01) and clinical symptoms improved. The overall ALT normalization response rate were 64.1% and 48.7% at the end of bicyclum treatment and 3 months after the treatment discontinued respectively for the total 39 patients. The serum HCV-RNA became negative in 5 and 2 patients at end of treatment and 3 months after the treatment discontinued. Adverse drug reactions were mild and uncommon. Mild dizziness occurred in 1 patient in each group.
Bicyclum is effective in improving ALT and clinical manifestations of CHC patients. It is safe and well tolerated and shows few adverse reactions.
Zhonghua yi xue za zhi 07/2002; 82(14):958-60.
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ABSTRACT: To search a novel sensitive, specific and lower cost method applicable for quantitative analysis of the hepatitis B virus DNA extensively.
Quantitative analysis of the DNA from 100 sera by real-time PCR with Sybr green 1. The results of Sybr's assay were compared with the results obtained with Taqman's fluorescent quantitative assay.
Taqman real-time PCR could help evaluate the level of virus reliably. The results of Sybr's assay were in agreement with the Taqman's assay, but detection rate was lower.
Sybr green 1 real-time PCR appeared to be convenient and cheap, but detection rate was lower.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 07/2002; 16(2):160-1.
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ABSTRACT: To search for genomic DNA sequence of the augmenter of liver regeneration (ALR) of rat.
Polymerase chain reaction (PCR) with specific primers was used to amplify the sequence from the rat genome.
A piece of genomic DNA sequence and a piece of pseudogene of rat ALR were identified. The lengths of the gene and pseudogene are 1508 bp and 442 bp, respectively. The ALR gene of rat includes 3 exons and 2 introns. The 442 bp DNA sequence may represent a pseudogene or a ALR-related peptide. Predicted amino acid sequence analysis showed that there were 14 different amino acid residues between the gene and pseudogene. ALR-related peptide is 84 amino acid residues in length and relates closely to ALR protein.
There might be a multigene family of ALR in rat.
Chinese Medical Sciences Journal 07/2002; 17(2):63-7.
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ABSTRACT: To construct recombinant vector expressing antisense RNA to CCR5 in eukaryotic cells and obtain recombinant pseudovirus, which will be used to block HIV-1 infection.
The DNA fragment targeted against the initional part of CCR 5 mRNA translation was amplified by using RT-PCR from peripheral blood mononuclear cells (PBMCs) and cloned into retroviral vector pLXSN, then transfected into packaging cell (PA317) with lipofectAMINE. After 2-3 weeks selecting with G418, the pseudovirion in the survival cell's supernatant was detected with RT-PCR (FQ),then was used to infect NIH/3T3 cell.
The psuedovirion packed from expression vector of sense/antisense RNA to CCR5 had infected NIH/3T3 cell successfully. The vector had incorporated into its genome and transcripted into RNA.
The gene fragment of antisense RNA to CCR5 could be obtained from PBMCs and transfected into eukaryotic cell with retroviral vector. The results made a great foundation for studying its inhibiting effect on HIV-1 infection.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 04/2002; 16(1):52-4.
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ABSTRACT: To investigate the HBV quasispecies groups in the patients with chronic HBV infection.
Specific primers ware synthesized according to HBV strain found in China, the preC/C gene, reverse transcriptase region, whole S region, X gene and whole genome ware amplified by PCR method from the serum of 18 patients with chronic HBV infection, and then the PCR products were subcloned into pGEM Teasy vectors. Positive clones with target sequences were selected out for sequencing. Sequence comparison of the selected clones ware made to find the difference.
The homology between clones from one patient of preC/C gene, reverse transcriptase of polymerase region, whole S region, X gene and whole genome are 98.0% approximately 99.1%, 98.7% approximately 99.3%, 97.5% approximately 100%, 93.0% approximately 98.2% and 96.6% approximately 97.5%, respectively. There was a high-frequency A83 substitution and core antigen internal deletion (CID) in preC/C region. Substitution, deletion and frame-shift by insertion or deletion of short sequence were found in 4 open reading frames. Deletion in X gene (Core promoter, CP) will not only result in the polymorphism of X protein at the carboxyl end, but also regulate the expression of HBeAg. Coding sequence of truncated middle surface antigen and defective HBV genome could also be detected in this study.
There are HBV quasispecies groups in patients with chronic HBV infection. Hot deletion region in X region (CP) will influence the prognosis of the HBV infection. Individually characterized substitutions in amino acid sequence of viral protein is worthy of further study.
Zhonghua yi xue za zhi 02/2002; 82(2):81-5.
