Analysis of a randomized, double-blind, double-dummy, controlled, multicenter study confirmed the similar therapeutic efficacies of entecavir maleate and entecavir for treatment of HBeAg-positive chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB).</p><p><b>METHODS</b>The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded.</p><p><b>RESULTS</b>As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05).</p><p><b>CONCLUSION</b>Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.</p>

A randomized, double-blind, double-dummy, controlled, multicenter study of entecavir maleate versus entecavir for treatment of HBeAg-negative chronic hepatitis B: results at week 48 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of entecavir (ETV) maleate versus ETV in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).</p><p><b>METHODS</b>This was a randomized, double-blind, double-dummy, controlled, multicenter study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A; n = 26) or 0.5 mg/day ETV maleate (n = 31). Hepatitis B virus (HBV) DNA levels were measured at weeks 12, 24, and 48 by the Roche Cobas Ampliprep/Taqman PCR assay. Adverse events (AE) were recorded.</p><p><b>RESULTS</b>Baseline characteristics were similar between the two groups. At weeks 12, 24, and 48, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 4.24, 4.61 and 4.88 log10 IU/mL vs. B: 4.01, 4.50 and 4.99 log10 IU/mL, respectively; all P more than 0.05). Patients who achieved undetectable levels of serum HBV DNA (less than 20 IU/mL) at week 48 were similar in the two groups (A: 69.23% vs. B: 80.65%; P more than 0.05). Both groups achieved similar normalization of ALT at week 48 (A: 96.00% vs. B: 83.87%; P more than 0.05). The overall AE incidence was similar for the two groups (A: 22.22% vs. B: 9.38%; P more than 0.05).</p><p><b>CONCLUSION</b>Entecavir maleate and entecavir showed similar efficacy and safety in patients with HBeAg-negative CHB.</p>

Variants and quasispecies of reverse transcriptase region in polymerase gene of hepatitis B virus during lamivudine treatment / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the variants and quasispecies of reverse transcriptase region in polymerase gene of hepatitis B virus (HBV) during lamivudine treatment and their relationship with genotypes and viral loads.</p><p><b>METHODS</b>HBV DNA of 117 chronic hepatitis B patients treated with lamivudine were amplified by using PCR. The PCR products including the YMDD motif were sequenced by DNA sequencer, of which, HBV DNA viral loads of 99 patients were determined by real-time PCR and 64 samples were sequenced by Pyrosequencing.</p><p><b>RESULTS</b>In HBV YMDD variant group and no variant group, the HBV genotypes were 79.6% and 86.7% of type C, 18.5% and 12.7% of type B, 1.9% of A/B recombinant type and 2.6% of type D, respectively. The viral loads (log 10) were 6.5699 and 6.6165, respectively. There was no significant difference in HBV genotypes and viral loads between these two groups. The rtL180M variant was found in association with the rtM204I/V variant, HBV variants and wild-type in YMDD motif all existed together in these two groups.</p><p><b>CONCLUSIONS</b>HBV variants (quasispecies) in YMDD motif could be quantified by pyrosequencing, which would be a feasible measure during nucleoside or nucleotide analogue therapy against chronic HBV infection.</p>

Efficacy of antiviral treatment on intrahepatic HBV DNA and histology in HBeAg -positive chronic hepatitis B patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of antiviral agents on intrahepatic HBV DNA and histology in HBeAg-positive chronic hepatitis B patients.</p><p><b>METHODS</b>Thirty-five patients were treated with lamivudine, 16 with interferon alfa (INF-alpha), 24 with sequential Lamivudine and INF-alpha. The total duration of therapy was 12 months. Intrahepatic HBV DNA was measured quantitatively by real-time polymerase chain reaction.</p><p><b>RESULTS</b>There was significant change in all parameters of the groups of patients at the end of treatment (P < 0.05). The patients treated with sequential treatment had slightly higher HBeAg seroconversion rate (38.1%) than that of the other patients (P=0.1352). The baseline levels of intrahepatic HBV DNA in the patients with HBeAg seroconversion or undetectable serum HBV DNA were significantly lower than that of the other patients (P < 0.05).</p><p><b>CONCLUSION</b>Antiviral agents could effectively inhibit intrahepatic HBV DNA and improve hepatic histology. The patients with low baseline intrahepatic HBV DNA level may achieve better antiviral efficacy. Sequential treatment might produce high HBeAg seroconversion rate.</p>

Effects of antiviral agents on intrahepatic ccc DNA in HBeAg-positive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of antiviral agents on intrahepatic HBV covalently closed circular DNA (cccDNA) in HBeAg-positive chronic hepatitis B patients.</p><p><b>METHODS</b>Seventy-one HBeAg positive chronic hepatitis B patients were enrolled in this study. Lamivudine was administered to 35 patients for 48 weeks, sequential therapy with lamivudine-IFN alpha-2b to 24 of the 71 patients for 48 weeks, and interferon alpha (IFN alpha-2b) was administered to 12 for 24 weeks. All subjects were followed-up for 24 weeks. Serum HBV DNA, intrahepatic HBV DNA and cccDNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.</p><p><b>RESULTS</b>Forty-eight weeks of sequential lamivudine-IFN alpha-therapy and lamivudine monotherapy and 24 weeks of IFN alpha monotherapy reduced the intrahepatic HBV DNA to (4.7+/-1.1) log10, (4.6+/-1.5) log10 and (5.6+/-1.5) log10, and cccDNA to (3.4+/-1.3) log10, (3.8+/-1.1) log10 and (5.0+/-1.5) log10, significantly lower than therapy (P < 0.05). Seventeen of the 71 patients developed HBeAg seroconversion, and the reduction of cccDNA in the HBeAg seroconverted patients was significantly more than that of the HBeAg positive patients (P < 0.05). After 24 weeks of antiviral therapy withdrawal, 18 patients achieved sustained virological response, and the baseline intrahepatic cccDNA in the patients with sustained virological response was significantly lower than that of patients with virological rebound (P < 0.05). The change in intrahepatic cccDNA correlated positively with the reduction in intrahepatic HBV DNA (P < 0.05). The cccDNA levels correlated with the serum HBeAg titers at the end of the treatment (P < 0.01). Of the total 71 cases, HBV genotype C accounted for 85.9% (n = 61), and genotype B for 14.1% (n = 10). There was no significant difference in the changes of intrahepatic HBV DNA and cccDNA levels between HBV genotypes C and B (P >0.05).</p><p><b>CONCLUSIONS</b>Both 48 weeks of sequential lamivudine-IFN alpha and lamivudine monotherapy strongly reduced intrahepatic HBV DNA and cccDNA more than 24 weeks of IFN alpha monotherapy. Low baseline intrahepatic cccDNA levels might predict a good long-term efficacy of antiviral treatment. The reduction of intrahepatic cccDNA correlated positively with the changes of intrahepatic HBV DNA, and intrahepatic cccDNA levels correlated with serum HBeAg titers. HBV genotypes had no obvious influence on intrahepatic HBV DNA load or cccDNA load.</p>

Clinical characteristies and distribution of hepatitis B virus genotype and sub-genotype / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the distribution and virologic characteristics of HBV genotypes, sub-type and possible association with the severity of liver disease.</p><p><b>METHODS</b>884 patients infected with HBV were enrolled from 8 provinces in China. HBV genotype and sub-type was determined, using PCR-RFLP method.</p><p><b>RESULTS</b>The most common HBV genotypes were B (20.77% ) and C (78.22 % ) but only 1 patient showed genotypes D. We found sub-type Ba in patients with genotype B, C1 and C2 sub-type in patients with genotype C. Genotype C (83.62%) and sub-type C2 (90.32%) were predominant in northern China. Patients with genotype B were much younger than those with genotype C. There was no significant difference between patients with sub-type C1 and C2. There was no significant difference in liver function and serum HBV-DNA load between patients with genotype B and C,or between patients with sub type C1 and C2. However, hepatic inflammation and fibrosis score in patients with genotype B were significantly lower than those with genotype C.</p><p><b>CONCLUSION</b>There were no significantly differences in liver function and HBV-DNA load between patients with genotype B and C, or between patients with sub-type C1 and C2. Hepatic inflammation and fibrosis score in patients with genotype B were significantly lower than those with genotype C. Genotype C/sub-type C2 were preponderance in northern China.</p>

Establishment and application of a real-time PCR method to detect hepatitis B virus cccDNA quantitatively / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To establish a new method to detect HBV cccDNA quantitatively and to apply it to detect cccDNA in liver needle biopsy specimens of chronic hepatitis B patients.</p><p><b>METHODS</b>The sequences of HBV DNA genotypes A through G were analyzed. According to the different sequence structure of cccDNA and rcDNA, primes and probe were designed in highly conservative region outside the nick of cccDNA in order to amplify cccDNA but not rcDNA. The best conditions of this method were found after testing experiments. Also we checked its specificity and sensitivity and reproducibility. The products of PCR were sequenced in order to ascertain if it was the right region expected. To amplify with standard plasmid ranged from 10(2) to 10(10) copies/ml to measure the sensitivity and amplify in parallel with standard plasmid of 10(6) copies/ml for 30 replicates so as to measure its reproducibility. DNA was extracted from 32 needle liver biopsy specimens of chronic hepatitis B patients. The cccDNA was quantitatively detected with this method. The data of cccDNA obtained before and after therapy and their relationship with total HBV DNA were analyzed. RESULTS Results of sequencing showed that the PCR product was from the right region. The sensitivity was 10(3)-10(10) copies/ml. The Ct value was 29.69+/-0.31 and the coefficient of variability was 1.04 percent calculated from the data of 30 PCR reactions with standard plasmid. The percentage of decrease in serum HBV DNA, total HBV DNA in liver and cccDNA in liver were 0.49+/-0.17, 0.22+/-0.18 and 0.16+/-0.28 respectively. There is 47 percent-98 percent cccDNA in total HBV DNA in liver and the mean is 81.5 percent.</p><p><b>CONCLUSION</b>The method is good because of the simple and convenient operation, the high specificity, the wide linear detection range and the fine reproducibility. Therefore it can be used for both scientific research and clinical purpose. Lamividine can significantly inhibit serum HBV DNA by, but its inhibitory effect on cccDNA in liver was rather weak.</p>

An analysis of the pathohistology of liver tissues, clinical features and prognostic factors of chronic hepatitis B virus carriers / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the correlations between clinical features and liver pathohistological changes of chronic hepatitis B virus (HBV) carriers and to discuss the factors which may influence the prognosis.</p><p><b>METHODS</b>Ninety HBV carriers who had liver biopsies were enrolled in this study.</p><p><b>RESULTS</b>(1) The mean follow-up period of the patients was 118 weeks. (2) Fifty-four patients (60.0%) had G1 hepatitis and 21 (23.3%) had G2 hepatitis. The fibrosis stages were graded as S1(42) and S2(21). (3) There were significant age differences among S0, S1 and S2. (4) There were significant differences in aminotransferase levels between patients who had a normal liver histology and those who had mild hepatitis. (5) The grades of liver inflammation were not correlated with the titers of HBeAg and HBV DNA in sera. The stages of liver fibrosis were not correlated with the titers of HBVDNA in sera. Most of the HBeAg negative patients progressed to S2. (6) There were significant differences in spleen dimensions measured by ultrasonography between S0, S1 and S2 patients. (7) During the follow-up period serum aminotransferase (ALT) levels remained normal in 60 patients (group A); 22 patients had transient elevations (group B), and 8 patients had persistent increases (group C). There were significant differences of the ratios of S0 and S2 cases among patients in groups A, B and C. (8) Age and fibrosis stages were predictive factors of liver cirrhosis.</p><p><b>CONCLUSIONS</b>Most chronic HBV carriers had mild inflammatory histological changes in their livers and also had different degrees of liver fibrosis. This follow-up study shows that some of those carriers should have had antiviral therapy.</p>

Diammonium glycyrrhizinate does not affect efficacy of adefovir dipivoxil therapy in patients with HBeAg-positive chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of diammonium glycyrrhizinate on the antiviral therapy with adefovir dipivoxil (ADV) in patients with HBeAg-positive chronic hepatitis B.</p><p><b>METHODS</b>Patients with HBeAg-positive chronic hepatitis B enrolled in this study were randomized to receive either ADV 10 mg/d fir 48 weeks or placebo for 24 weeks followed by ADV 10 mg/d for 24 weeks. Antiviral activities of diammonium glycyrrhizinate administered during the trial were studied with respect to virological and serologic response, and ALT normalization.</p><p><b>RESULTS</b>Twenty-one of 142 patients in ADV group vs. 11 of 68 patients in placebo group were treated with diammonium glycyrrhizinate. There was no significant difference in virological, serological and biochemical responses between patients with or without diammonium glycyrrhizinate in both therapy groups. During double-blind period, virological response was significantly worse in patients only receiving diammonium glycyrrhizinate than those combined with ADV.</p><p><b>CONCLUSION</b>Diammonium glycyrrhizinate had no antiviral activity and exerts no influence on the efficacy of ADV treatment in patients with HBeAg-positive chronic hepatitis B.</p>

Efficacy of adefovir dipivoxil was not related to genotypes B and C of hepatitis B virus: a randomized, double-blind, multicenter clinical study / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To determine the relationship between the response to adefovir dipivoxil (ADV) treatment in patients with HBV genotypes B and C of HBeAg positive chronic hepatitis B.</p><p><b>METHODS</b>This clinical trial was a randomized, double-blind, placebo-controlled, multicenter study. A total of 226 eligible patients with HBeAg positive chronic hepatitis B were randomized (in a ratio of 2:1) receiving ADV 10 mg/d for 48 weeks (ADV+ADV group) or placebo for 24 weeks followed by ADV 10 mg/d for 24 weeks (PLB+ADV group). The primary efficacy was virologic response. The genotypes of HBV were determined by PCR-restricted fragment length polymorphism (RFLP) method using serum samples before therapy. rtN236T and rtA181V mutations were confirmed by sequencing.</p><p><b>RESULTS</b>In this study, HBV genotype C was 66.7%, genotype B was 25.2%. Genotype B was more common in Guangzhou. Patients with genotype B were much younger than those with the genotype C. Patients with genotype B previously received less anti-HBV therapy. There were no significant difference in virological response (including mean reduction in HBV DNA level from baseline, serum HBV DNA load after treatment and HBV DNA undetectable rate) and serological response (the rate of HBeAg loss and HBeAg seroconversion) between patients infected with genotypes B and C in both treatment arms.</p><p><b>CONCLUSION</b>There were no significant difference in virological and serological response to ADV therapy between patients infected with HBV genotype B and C.</p>

A multicenter, randomized, open-label study of the safety and effectiveness of pegylated interferon alpha 2b and interferon alpha 2b in treating HBeAg positive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of PEG-IFNalpha-2b (Peg-Intron) with IFNalpha-2b (Intron A) in treating HBeAg positive chronic hepatitis B patients.</p><p><b>METHODS</b>Two hundred thirty chronic hepatitis B (CHB) patients eligible to the following criteria were enrolled into this study: HBsAg and HBeAg(Abbott kit) positive for at least 6 months, serum HBV DNA > or =10(5) copies/ml (real time PCR, LLQ <10(3) copies/ml) and ALT > or =2 x ULN. After 1:1 randomization, the patients received PegIntron (group A: 1.0 microg/kg body weight, SC, once a week) or Intron A (group B: 3 MIU SC, three times a week) for 24 weeks, and followed up for 24 weeks.</p><p><b>RESULTS</b>(1) In groups A and B, respectively, 80.87% and 83.48% were males; their median ages were 31.0 and 32.0 years old; their median body weights were 65.6 and 65.5 kg; mean serum HBV DNA loads were 8.06 log10 and 7.99 log10; their mean ALT values were 4.17 x ULN and 3.77 x ULN. All of the above parameters between the two groups had no statistically significance differences. (2) At the end of treatment and after follow-up, compared to the Intron A group, the PegIntron group showed better response (including complete and partial response rate, HBV DNA undetectable rate, HBeAg seroconversion rate), but the differences of all of them had no statistical significance. The rate of HBeAg loss was higher in patients receiving PegIntron after follow-up (P = 0.0424). (Table 2) (3) PegIntron and Intron A reduced serum HBV DAN persistently during the therapy. Mean reduction at the end of the treatment was much higher in the PegIntron group than in the Intron group (2.22 log10 copies/ml vs 1.66 log10 copies/ml, P = 0.0283). (4) The overall incidence of adverse events (AEs) in the PegIntron group was similar to that of the Intron A group (94.78% vs 95.65%). The AEs associated with PegIntron administration were similar in nature to those with Interon A, such as influenza-like symptoms, fever, fatigue, headache, nausea, etc and the differences of their incidences had no statistical significance.</p><p><b>CONCLUSIONS</b>The efficacy and safety of PEG-IFNalpha-2b treatment for CHB patients seems to be better than that of IFNalpha-2b; however, further studies are needed to confirm it.</p>

A clinical study of adefovir dipivoxil, made in China, for treatment of hepatitis B e antigen-positive patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of a China made adefovir dipivoxil (ADV) treatment for hepatitis B e antigen-positive patients with chronic hepatitis B.</p><p><b>METHODS</b>Two hundred and thirty patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) were randomly put into groups A or B, and 58 patients with lamivudine-resistant chronic hepatitis B were randomly put into groups C or D. During the first 12 weeks of the trial, 112 patients in group A and 115 patients in group B received 10 mg of ADV and a placebo once a day; 28 patients in group C received 100 mg of lamivudine (LMV) and 10 mg of ADV; 29 patients in group D received 100 mg of LMV and a placebo once a day. In the second trial period, all patients received ADV for 36 weeks. The primary checking criterion was the serum HBV DNA change during the treatment. The secondary ones were alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion.</p><p><b>RESULTS</b>At week 12, the median serum hepatitis B virus (HBV) DNA level of group A (ADV-ADV) was reduced 2.8 log10 copies/ml, significantly greater than that of group B (placebo-ADV) of 0.3 log10 copies/ml reduction (P = 0.000). At week 48, the median serum HBV DNA level of group A and group B were reduced 3.6 and 3.4 log10 copies/ml respectively. At week 12, the median serum HBV DNA level of group C (LMV+ADV) was reduced 3.0 log10 copies/ml, significantly greater than that of the group D (LMV+placebo) of 0.16 log10 copies/ml reduction (P = 0.000). At week 48, the median serum HBV DNA level of group C and group D were reduced 3.6 and 3.8 log10 copies/ml respectively. Only 5.56% (16/288) patients had adverse events that were mild to moderate. There was no significant difference in the change of serum creatinine compared with their baseline levels.</p><p><b>CONCLUSION</b>In our HBeAg positive lamivudine-resistant chronic hepatitis B patients, 48 weeks of ADV treatment was safe and resulted in significant virological and biochemical improvements.</p>

Foscarnet sodium for treatment in patients with severe chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effectiveness of foscarnet sodium in the treatment of severe chronic hepatitis B.</p><p><b>METHODS</b>Two hundred and eight patients were enrolled in a multicenter, double-blind, controlled study. The patients received foscarnet sodium (foscarnet group) or saline (control group) injections for 4 weeks, and were then followed for 24 weeks.</p><p><b>RESULTS</b>HBV DNA negative rate was 12.8% in the foscarnet group and 7.1% in the control group at the end of treatment; and it was 5.5% and 3.0% at the end of the follow-up period respectively (P > 0.05). The rate of HBV DNA decrease of more than 2 log copies/ml was 53.2% in the foscarnet group and 16.2% in the control group at the end of treatment, and 23.9% and 8.1% (P < 0.01) respectively at the end of the follow-up period. The rate of HBV DNA < 10(5) copies/ml was 64.2% and 30.3% at week 4 in the two groups respectively, and 40.4% and 22.2% (P < 0.01) at the end of the follow-up period. HBeAg negative rate was 17.3% and 5.8% at the end of the treatment, and 22% and 5.4% at the end of the follow-up period (P < 0.01). The rate of HBeAg seroconversion was 12.7% and 3.7% at week 4, and 16.7% and 1.5% at the end of the follow-up period. Response rate was 60.6% and 21.2% at the end of week 4 (P < 0.05).</p><p><b>CONCLUSION</b>Foscarnet sodium injection has a good effect on severe chronic hepatitis B patients and it is safe to use on them.</p>

Serum HBV-DNA level can predict treatment effectiveness in patients with chronic hepatitis B using interferon-alpha-2a / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the correlation between the efficacy of interferon-alpha-2a and the kinetics of viral load in serum.</p><p><b>METHODS</b>The authors conducted a trial including 58 patients with chronic hepatitis B. Patients were treated with interferon-alpha-2a three times a week for 6 months. Viral kinetics were assessed by serial quantitive measurements of HBV-DNA.</p><p><b>RESULTS</b>A significant decline of serum HBV-DNA was seen after interferon-alpha-2a administration for 1 month, the decreases were (2.50 +/- 0.44) log10, (1.62 +/- 1.12) log10 and (1.05 +/- 1.35) log10 for complete responders, partial responders and no-responders, respectively. After 1 month of treatment, HBV-DNA level was (3.99 +/- 0.91) log10 for complete responders versus (5.63 +/- 1.31) log10 for partial responders, and (6.69 +/- 1.42) log10 for no-responders (P < 0.05). Multivariate analysis suggested that undetectable serum HBV-DNA after 1 month of interferon-alpha-2a treatment was associated with better efficacy; higher baseline ALT or/and no family history were also correlated with better treatment outcomes.</p><p><b>CONCLUSION</b>Kinetics of HBV-DNA level under interferon-alpha-2a treatment are highly predictive of therapeutic response.</p>

Inhibition of hepatitis C virus gene expression by antisense nucleotide in vitro / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the mechanism of hepatitis C virus (HCV) gene regulation and the inhibitory effect of antisense RNA on HCV gene expression in vitro.</p><p><b>METHODS</b>The hepatoblastoma cell line (HepG2) was co-transfected by recombinant plasmid of antisense RNA complementary to HCV 5' untranslated region (5'UTR)and HCV 5' UTR Directed luciferase (luc) gene expression recombinant plasmid. Meanwhile a reversed HCV 5'UTR recombinant plasmid which can not transcribe as antisense RNA in the cell and a recombinant plasmid in which the luc was regulated by simian virus 40 (sv40) 5'UTR were used as controls respectively. The level of luc gene expression was determined by an enzymatic assay.</p><p><b>RESULTS</b>The antisense RNA which directed to HCV 5'UTRcould obviously knock down the level of luc gene expression and the close-dependent inhibition of antisense RNA was observed at the same time. However the above inhibition was not shown in the cells co-transfected by reversed HCV 5'UTR recombinant plasmid and HCV 5'UTR directed luc gene expression recombinant plasmid. No reduction was observed in luc gene expression level in the cell co-transfected by both antisense RNA recombinant plasmid and SV40 5'UTR directed luc gene expression recombinant plasmid.</p><p><b>CONCLUSION</b>HCV 5'UTR plays an important role in regulation of viral gene expression. The antisense RNA complementary to HCV 5'UTR could effectively inhibit the gene expression regulated by HCV 5'UTR in vitro.</p>

Clinical study on patients at early stage of severe acute respiratory syndrome / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To elucidate the clinical features of patients at early stage of severe acute respiratory syndrome (SARS).</p><p><b>METHODS</b>Fifty-three cases of early SARS were studied retrospectively. The data reviewed included those of epidemiology, clinical manifestations, laboratory investigation and roentgenology.</p><p><b>RESULTS</b>The patients consisted of 24 men and 29 women, aged 10.85 years (mean 38+/-16.7 years), including 9 infected health-care professionals (17.0%). The mean incubation period was 7.3+/-7.0 days (3.14 days). The onset symptoms were characterized by fever (100%), cough (49.1%), maylgia (24.5%), shortness of breath (20.8%), malaise (17.0%),and diarrhea (5.7%). Routine blood test during the first to the fifth day of the disease revealed WBCs less than 4.0x10(9) /L in 33 patients (62.3%), 4.0-10.0x10(9)/L in 18 patients (34.0%), lymphopenia in 36 patients (67.9%), and PLT less than 100.0x10(9) in 7 patients (13.2%). The main abnormal X-ray finding was single (75.4%) or bilateral (15.1%) localized patchy clouding opacity. The decrease of arterial partial pressure of oxygen occurred in 26 patients (49.1%). The damage of several organs was common, including the elevated ALT or AST in 20 patients (37.7%), elevated BUN or SCR in 6 patients (11.3%) and elevated LDH or CK or HBDH in 23 patients (43.4%).</p><p><b>CONCLUSION</b>The clinical manifestations of SARS at the early stage were complex. The close monitoring of the blood cell counts, the blood gas analysis and chest radiography might be crucial to the early diagnosis.</p>

A randomized,double-blind,multicenter study of adefovir dipivoxii in treating patients with HBeAg-positive chronic hepatitis B / 中华传染病杂志

Objective To evaluate the efficacy and safety of adefovir dipivoxil(ADV)in treating patients with hepatitis B e antigen(HBeAg)positive chronic hepatitis B.Methods In this randomized,double blind,placebo-controlled,multicenter trial,210 eligible patients with HBeAg positive chronic hepatitis B were recruited and randomized(randomization ratio was 2:1)receiving ADV 10 mg/d for 48 weeks(ADV+ADV group,n=142)or placebo for 24 weeks followed by ADV 10 mg/d for 24 weeks(PLB+ADV group,n=68).The primary endpoint was virological response. The secondary endpoint was serologic response(HBeAg loss rate and HBeAg seroconversion rate) and alanine aminotransferase normalization rate.Results After 24 weeks therapy,mean reduction of hepatitis B virus(HBV)DNA level comparing with that of baseline was 3.12 log_(10)copy/mL in ADV +ADV group while it was 0.95 log_(10)copy/mL in PLB+ADV group.The percentages of patients with HBV DNA clearance(HBV DNA level