Efficacy of pegylated-interferon alpha-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy.</p><p><b>METHODS</b>Patients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software.</p><p><b>RESULTS</b>A total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%.</p><p><b>CONCLUSION</b>Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.</p>

Comparative analysis of the efficacies of entecavir capsules and lamivudine in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy profile of entecavir capsule (ETV) as a chronic hepatitis B therapy, as compared to lamivudine (LAM).</p><p><b>METHODS</b>In this multicenter, randomized, double-blind, parallel group evaluation of ETV, 232 subjects were administered a 96-week course of 0.5 mg/day ETV or 100 mg/day LAM. PCR measurement of hepatitis B virus (HBV) was conducted throughout the treatment course to determine achievement of complete virologic response (CVR; defined as less than 500 copies/ml of HBV DNA) or experience of virology rebound ( more than 500 copies/ml of HBV DNA after achievement of CVR).</p><p><b>RESULTS</b>After week-48 of treatment, the ETV group showed a higher CVR rate (90.3% vs. LAM: 59.4%) and lower virology rebound rate (1.9% vs. LAM: 13.9%). After week-96 of treatment, the ETV group continued to have a higher CVR rate (86.0% vs. LAM: 71.4%), and virology rebound was experienced by significantly less subjects in the ETV group (1.2% vs. LAM: 11.9%, P = 0.005).</p><p><b>CONCLUSION</b>ETV therapy can quickly and continuously suppress HBV replication in chronic hepatitis B patients, and has a lower resistance rate than LAM. Compared to LAM, ETV may be a superior long-term treatment choice for chronic hepatitis B.</p>

Study on the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011.</p><p><b>METHODS</b>We summed up the changes in the characteristics of the etiology of acute hepatitis of patients mentioned above, and preliminarily analyze the causes.</p><p><b>RESULTS</b>From 2002 to 2011, 6235 patients with acute hepatitis were admitted to Ditan Hospital, aged between 12 and 78 years old, Of which 4309 were male and 1926 female. Acute viral hepatitis accounted for 70.44%-85.07%, while CMV, EBV, drug-induced liver injury accounted less than 5%, and acute hepatitis D and acute hepatitis C less than 1.10%. From year to year, the incidence and constitution of acute hepatitis changed significantly. The proportion of patients with acute hepatitis in total hospitalized patients was from 20. 38% to 2.05%. In 10 years, the percentage of acute hepatitis A decreased most obviously, about 99.11%, while 45.07% decline in incidence of acute hepatitis B and 62. 28% of acute hepatitis E. The constituent ratio of acute hepatitis also changed significantly. The proportion of acute hepatitis A declined from 31.31% in 2002, to less than 1% in 2011. The proportion of acute hepatitis B increased from 26.47% in 2002 to 45.88% in 2011, an increase of about 2 folds in 10 years. The proportion of acute hepatitis E increased from 26.73% in 2002 to 32.05% in 2010, a rise of 1.20 times in 10 years.</p><p><b>CONCLUSIONS</b>The proportion of patients with acute hepatitis in total hospitalized patients decreased from 20. 38% in 2002 to 2. 05% in 2011 in Beijing Ditan Hospital. The constituent ratio of acute hepatitis changed, too.</p>

Analyse related factors of impact and prognosis of 73 cases of severe hepatitis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>A retrospective study was conducted to investigate the clinical features and prognostic factors of 73 cases of severe hepatitis.</p><p><b>METHODS</b>To summarize clinical features of 73 cases of severe hepatitis, grouping by etiology and pathogenesis. A retrospective analysis was performed to evaluate the relationship between biochemical characteristics (liver function, renal function, electrolytes, PTA, etc) and complications (hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, ascites, abdominal infections, etc) and prognosis.</p><p><b>RESULTS</b>(1) HBV infection alone accounted for 65.75%. Alcoholic liver disease, drug-induced liver injury, hepatitis E, autoimmune hepatitis, overlapping causes and other factors were five cases (6.85%), six cases (8.22%), two cases (2.74%), two cases (2.74%), seven cases (9.59%) and three cases (4.11%) respectively. According to the incidence rate, severity and underlying liver condition, subacute hepatitis, cases based on chronic hepatitis and on cirrhosis were 12 cases (16.43%), 11 cases (15.07%), 50 cases (68.49%) respectively. Clinical manifestations with or without hepatic encephalopathy accounted for 58.90% or 41.10%. (2) The highest mortality of severe hepatitis was alcoholic liver disease and patients on the basis of overlapping factors (66.67%), followed by autoimmune liver disease (50%). The mortality of HBV-related hepatitis was 18.75%. Overall mortality of 73 cases of severe hepatitis was 28.77%, of which cirrhosis group was higher than non-cirrhotic group (40% vs 4.3%, P = 0.002). The difference was statistically significant. Patients without hepatic encephalopathy had lower mortality than with hepatic encephalopathy (3.33% vs 46.51%). The mortality of patients with hepatic encephalopathy Stage III and IV was 72.73%. (3) Independent samples t test filtered nine factors associated with death, namely cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, serum creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB) and serum sodium. The results of multivariate conditional logistic regression analysis indicated that hepatic encephalopathy, serum creatinine levels were risk factors for death, whereas ALB as a protective factor.</p><p><b>CONCLUSION</b>Hepatic encephalopathy, serum creatinine levels were risk factors for severe hepatitis death, But ALB was protective factor. Nucleotide analogs using was the main reason why the mortality of hepatitis B was as low as 18.75%.</p>

Study on retreatment of CHC patients with initial treatment failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the retreatment of CHC patients with initial treatment failure and how to achieve SVR.</p><p><b>METHODS</b>54 patients who had experienced treatment failure were enrolled and retreated with standard treatment of pegylated interferon and ribavirin or intensive treatment, respectively. Their SVR rates were statistically compared, to decide two therapies' application.</p><p><b>RESULTS</b>54 patients had been retreated, and total SVR rate was up to 75.92%, with 88.46% in relapsed patients and 64.29% in non-responders. After retreatment with pegylated interferon and ribavirin, SVR rate was 95.45% in patients with prior interferon monotherapy, and 64.71% in patients with prior interferon and ribavirin, and 60% in patients with prior pegylated interferon alpha-2a monotherapy. SVR rate of relapsed patients was significantly higher than that of non-responders.</p><p><b>CONCLUSIONS</b>In CHC patients with treatment failure, SVR rate of retreatment with standard treatment or intensive treatment still can be up to 60%-90%. Retreatment with standard therapy can be applied to patients who had received interferon monotherapy or interferon plus ribavirin. Three types of patients who need intensive retreatment were as following: patients nonresponsive to interferon plus ribavirin or pegylated interferon alpha-2a monotherapy, and patients with treatment failure who had received prior standard treatment.</p>

High rates of HBsAg loss and seroconversion result from prolonged course of pegasys treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>HBsAg loss and seroconversion in patients with chronic hepatitis B leads to long-lasting good clinical outcomes. The aim of this paper was to investigate to improve the rate of HBsAg loss and seroconversion in chronic hepatitis B patients by prolonged treatment of PEG-IFNa-2a. 217 cases of HBeAg-positive or negative patients were collected from inpatient and outpatient in Beijing Ditan Hospital from May 2005 to October 2009 and subcutaneous injection of 135 ug or 180 ug PEGASYS were given once a week according to body weights. The drug doses were adjusted according to the neutrophilic granulocyte and platelet counts during treatment course. Quantitative HBV DNA test was conducted using a commercially available real-time fluorescence quantitative PCR kit. The serum HBsAg/anti-HBs and HBeAg/anti-HBe were quantitatively detected by Abbott i 2000 chemiluminescent kit before and during treatment every three months. Patients with HBsAg steadily decreased and reached serum HBsAg level below 200 IU/ml after 48 weeks of treatment would receive prolonged treatment. Patients with more than 12 weeks of treatment entered into analysis. Main efficacy of prolonged treatment was evaluated by the incidences of HBsAg loss and seroconversion.</p><p><b>RESULTS</b>The treatment courses of the 217 patients ranged from 12.0 to 197.6 weeks with an average of 53.1+/-33.4 weeks, 118 cases took more than 48 weeks and another 89 cases less than 48 weeks. 13.4% (29/217) of patients achieved HBsAg loss or HBsAg seroconversion with treatment courses from 17.6 to 197.6 weeks (average 75.4+/-42.8 weeks). Among these 29 patients 24 (82.8%) received more than 48 weeks of treatment, but the treatment courses of HBV DNA reached undetectable level were 20.8+/-8.9 weeks. In this study, 9.5% (14/148) of HBeAg-positive patients achieved HBsAg loss or seroconversion, all of them treated more than 48 weeks, from 48 to 194 weeks, average 81.32+/-39.36 weeks. 21.7% (15/69) of HBeAg-negative patients achieved HBsAg loss or seroconversion, significantly higher than that of HBeAg-positive patients (9.5%) (x2 = 6.129, P = 0.013). The average treatment course for HBeAg-negative patients with HBsAg loss was 70.2+/-48.0 weeks, shorter than that of HBeAg-positive patients with HBsAg loss (81.3+/-39.4 weeks), but no significant difference (t = -0.522, P = 0.602) found between.</p><p><b>CONCLUSION</b>Higher rate of HBsAg loss and seroconversion could be obtained by individual extended treatment courses in patients with rapid HBV DNA and HBsAg response to PEG-IFNa-2a treatment and the HBeAg-negative patients could got higher rate of HBsAg loss than HBeAg-positive patients.</p>

The relationship of serum HBsAg, HBeAg concentration and HBV-DNA load in chronic hepatitis B during IFN treatment / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relation of serum HBsAg, HBeAg contents and HBV-DNA load changes in HBeAg-positive chronic hepatitis B during IFN-alpha treatment.</p><p><b>METHODS</b>After enrolled, the patients were treated with 3MU-5MU IFN subcutaneous injection every two days, and their serum was collected before treatment and every 3 months during the treatment course. The serum HBV-DNA load was determined by real-time fluorescence quantitative PCR method kit (lower detection limit 500 copies/ml, Piji company, Shenzhen city, China,) according to production instruction, and HBeAg and HBsAg contents were detected by ARCHITECH I 2000.chemiluminescent kit. The relation of serum HBV-DNA, HBeAg and HBsAg content was analyzed by SPSS statistic software.</p><p><b>RESULTS</b>There were 228 patients enrolled into this group, male 162 cases, female 66 cases, aged 14-60 years, average 30.94 years old. After IFN treatment the HBV-DNA, HBeAg and HBsAg levels were all gradually decreased. But there was no relation of HBsAg content to HBV DNA and HBeAg content before and during treatment course(P > 0.05). However the serum HBeAg content was related to HBV-DNA content significantly (P < 0.05) and their changes was correspondence.</p><p><b>CONCLUSION</b>Before and during treatment of interferon, HBeAg and HBV-DNA content changes are closely related, while there is no significant correlation between HBsAg and HBeAg and HBV-DNA content. During interferon therapy, HBsAg, HBeAg, HBV-DNA contents should be detected together.</p>

Studies about the level of CD4+ CD25+ regulatory T cells and relation between expression of Foxp3 and CD127 in peripheral blood of chronic HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the level of CD4+ CD25+ Foxp3+ regulatory T cells and observe relation between expression of Foxp3 and CD127 in peripheral blood of chronic HBV infection.</p><p><b>METHODS</b>CD4+ CD25+ Foxp3+ and CD4+ CD25+ CD127low Treg in peripheral blood from 34 patients of immune tolerance stage, 26 patients of immune clearance stage and 31 patients of non-active status were quantitatively analyzed by flow cytometry.</p><p><b>RESULTS</b>Immune tolerance group presented a higher fraction of CD4+ CD25+ Foxp3+ and CD4+ CD25+ CD127low Treg than non-active group in chronic HBV infection (Z = -2.693, P = 0.007 and t = 3.251, P = 0.002), and HBV positive group also presented a higher fraction than non-active group (t = 2.266, P = 0.026 and t = 3.208, P = 0.002), But ALT normal group is similar to ALT abnormal group (P > 0.05). In this study, the relation between expression of CD127low and Foxp3+ from CD4+ CD25+ regulatory T cells was observed, and CD4+ CD25+ CD127low Treg presented a higher fraction than CD4+ CD25+ Foxp3+ Treg.</p><p><b>CONCLUSION</b>Peripheral Treg in HBV active replication group is higher than HBV negative group of chronic HBV infection. Expression of CD127low is consistent with Foxp3+ in CD4+ CD25+ regulatory T cells, but the former is significantly higher than the latter.</p>

Results of 3 years of continuous entecavir treatment in nucleos(t)ide-naive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the virological, serological and biochemical outcomes of 3 years of entecavir (ETV) treatment in nucleoside-naive chronic hepatitis B patients.</p><p><b>METHODS</b>This study was divided into two stages: Patients receiving either ETV 0.5 mg/d (n = 258) or lamivudine (LAM) 100 mg/d (n = 261) entered the initial 96-week randomized, double blind, controlled efficacy study. Patients not achieving a consolidated response (HBV DNA less than 0.7 MEq/ml, ALT less than 1.25 times*ULN, and if HBeAg-positive at baseline, loss of HBeAg for >or= 24 weeks), or those experienced viral breakthrough or relapse, entered a 48-week entecavir rollover study.</p><p><b>RESULTS</b>96 weeks after the treatment, 79% of ETV treated and 46% of LAM treated patients had HBV DNA less than 300 copies/ml (P < 0.0001), 96% of ETV treated and 92% of LAM treated patients had normalized ALT (P = 0.06). 21% of ETV treated and 23% of LAM treated patients achieved HBeAg seroconversion. Among the 160 patients received continuous ETV for 144 weeks, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, and 27% achieved HBeAg seroconversion. ETV resistance was rare: only 3 patients showed ETV resistance 96 weeks after the treatment, and additional 2 patients developed ETV resistance during the following 48 weeks, genotyping indicated the ETV resistance was caused by gene mutation. Adverse event rates in ETV-treated patients were similar to those in LAM-treated patients, but fewer ALT flares were observed in ETV-treated patients.</p><p><b>CONCLUSIONS</b>This study demonstrates that ETV treatment results in long-term HBV suppression and ALT normalization in Chinese CHB patients, and is associated with low rate of drug resistance.</p>

Prediction of sustained viral response to combinational therapy with interferon and ribavirin in chronic hepatitis C by rapid viral response / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate whether the rapid viral response (RVR) to combinational therapy with interferon and rabavirin can be used to predict the sustained viral response (SVR) in chronic hepatitis C patients.</p><p><b>METHODS</b>According to their clinical characteristics, all patients in this study were given pegylated or conventional interferon injection and different dose of ribavirin according to their weight. Patients were injected Pegasys (pegierferon alpha-2a) 180 microg or 135 microg once a week, or pegyintron 50-80 microg once a week, or conventional interferon 3-5 MU every two days, in combination with a dose of 600-1500 mg/d ribavirin. The serum HCV RNA load was determined at 0, 4, 12 week, and then every 12 weeks. After the viral response obtained, the patients were treated for another 24-72 weeks and followed up 24 weeks. The main parameter to evaluate the efficacy was SVR rate. The influence factors associated with rapid viral response were investigated.</p><p><b>RESULTS</b>RVR was obtained at week 4 in 84.2% of the 120 patients. The HCV RNA baseline of RVR group was (5.883+/-1.246) lg copies/ml, which was significantly lower than that of the group without RVR [(6.502+/-0.693) lg copies/ml, t=2.15, P=0.034]. 97 patients with RVR who finished treatment and follow-up, 90.7% of these patients obtained SVR, but the SVR rate in patients (82.4%) without RVR was lower than that in patients with RVR (x2=0.371, P=0.543). In this study, RVR rate was not associated with HCV genotype and the dose of interferon used. In the naive patients, the RVR to pegylated interferon was 87.8%, which was significantly higher than that in retreat patients (x2=4.651, P=0.031).</p><p><b>CONCLUSION</b>High RVR rate could be obtained in chronic hepatitis C patients treated combined with interferon and ribavirin. RVR rate is associated with the HCV RNA baseline load in both naive and retreat patients but not correlated to HCV genotype. RVR could predict the SVR.</p>

Expression of intrahepatic CD4+ CD25+ regulatory T cells in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression and distribution of intrahepatic CD4+ CD25+ regulatory T cells in immuno-tolerant and immuno-clearance phase of patients with chronic hepatitis B.</p><p><b>METHODS</b>The expression of FoxP3 was detected in 19 cases of immuno-tolerant phase and 12 cases of immuno-clearance phase by immunohistochemistry. The relation between the intrahepatic expression of FoxP3 and the clinicopathological features were analyzed.</p><p><b>RESULTS</b>The positive signal of FoxP3 is located in nuclear of lymphocyte and mainly aggregated in portal areas as well as occasionally scattered in hepatic sinusoids. The expression of intrahepatic FoxP3 in the group of immuno-tolerant phase was significantly increased than those in normal control (P < 0.01), and greatly decreased than those in immuno-clearance phase (P < 0.01). No correlation was observed among the expression of intrahepatic FoxP3, ALT, levels of HBV DNA, HBeAg positive, in patients of immuno-clearance phase, respectively. There were significant differences between immuno-tolerant phase and immuno-clearance phase age, ALT, TBIL, PTA, HBV-DNA and detection of HBeAg but not in sex and family history of HBV infection.</p><p><b>CONCLUSION</b>CD4+ CD25+ regulatory T cells may play important roles in the clearance of HBV as well as in liver inflammation and injury during chronic HBV infection.</p>

The degree of HBV suppression with 24 week telbivudine- or lamivudine-treatment in hepatitis B patients predicts the efficacy of the treatment at week 52 / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy.</p><p><b>METHODS</b>In this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again.</p><p><b>RESULTS</b>At week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition.</p><p><b>CONCLUSION</b>HBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.</p>

Factors associated with HBeAg seroconversion in chronic hepatitis B patients treated with interferon alfa-2a / 中华肝脏病杂志

<p><b>OBJECTIVE</b>The aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients.</p><p><b>METHODS</b>PEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed.</p><p><b>RESULTS</b>The differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01).</p><p><b>CONCLUSIONS</b>Viral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.</p>

Effect of hepatitis C virus serotype on the response of patients with chronic hepatitis C to interferon treatment / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the influence of hepatitis C virus (HCV) serotype on the interferon (IFN) treatment of patients with chronic hepatitis C.</p><p><b>METHODS</b>Ninety-eight patients with chronic hepatitis C were divided into two groups: patients in group 1 (n=53) were treated with Pegasys, 180 ug injected subcutaneously once a week for 24 weeks, and those in group 2 (n=45) were injected with Roferon-A 3 MU three times a week for 24 weeks and then patients in both groups were followed up for another 24 weeks. The virological response at the end of follow up was the primary endpoint for evaluating the effects of IFN treatment. The HCV RNA levels of the chronic hepatitis C patients were determined with COBAS AMPLICOR MONITOR Test, version 2.0, and the HCV serotypes were examined by the means of ELISA using Murex HCV Serotyping 1-6 Assay.</p><p><b>RESULTS</b>Of the 98 cases, HCV in 44 cases was serotype 1, in 23 was serotype 2, in 10 was serotype 3, in 1 was serotype 4, 1 was serotype 5 and in 2 was serotype 6; HCV serotypes in the remaining 17 patients could not determined. In Pegasys treatment group, the biochemical and virological response was not significantly different at the end of treatment between the patients with serotype 1 and non serotype 1 or serotype undetermined patients, but the sustained virological response rate of HCV serotype undetermined group (66.7 percent) was significantly higher than that of serotype 1 patients (27.3 percent) (p=0.035). In Roferon-A treatment group, the virological response rate at 24 weeks and sustained viral response rate at the end of follow-up was not significantly different between serotype 1 and non serotype 1 patients or serotype undetermined patients.</p><p><b>CONCLUSION</b>After the six months treatment course, the HCV serotype had some effects on the treatment response to Pegasys treatment for chronic hepatitic C.</p>

Concordance between hepatitis C virus serotype and genotype in chronic hepatitis C patients in China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of hepatitis C virus (HCV) serotype with genotype.</p><p><b>METHODS</b>The serotypes of HCV in the serum of 104 patients with chronic hepatitis C from 14 cities in China for which HCV genotypes were available, were determined by ELISA using Murex HCV Serotyping 1-6 Assay.</p><p><b>RESULTS</b>The serotypes of 86 (82.69 percent) of the 104 serum specimens were determined, and HCV serotypes were determined for 91 strains. Overall the concordance between hepatitis C virus serotype and genotype was 62.1 percent, and the concordance of serotype, with genotypes 1, 2 and 3 were 69.4 percent, 51.2 percent and 70.0 percent, respectively. The false-negative rate and concordance of genotype 2b was lower (54.5 percent).</p><p><b>CONCLUSION</b>The specificity of HCV serotyping was affected by HCV strains' genotype and sometimes HCV serotype was not in concordance with genotype.</p>

The impact of HBeAg positivity/negativity and HBV DNA loads on the prognosis of chronic severe hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the impact of HBeAg positivity/negativity and HBV DNA loads on the prognosis of chronic severe hepatitis B.</p><p><b>METHODS</b>206 patients with chronic severe hepatitis B hospitalized in Beijing Ditan Hospital from July 2002 to Dec. 2004 were analyzed. HBeAg positivity/negativity, HBV DNA loads and other factors relating to the prognosis of the patients were studied with univariate and multivariate analyses.</p><p><b>RESULTS</b>Chi2 univariate analysis showed that there was no significant difference in the prognosis between different HBeAg groups (chi2 = 0.440, OR = 0.777, 95% CI 0.424-1.425, P = 0.50). But there was a significant difference in the prognosis between different HBV DNA load groups: the prognosis of patients with lower HBV DNA loads was better than those with higher loads (chi2 = 9.806, OR = 3.055, 95% CI 1.554-6.007, P = 0.002), and the improving rates of the two groups were 53.1% and 27.0% respectively. Using multivariate logistic regression analysis, 9 screened factors showed great impact on the prognosis of chronic severe hepatitis B. Cirrhosis, hepatorenal syndrome, hepatic encephalopathy, PTA < 20%, TBil > 513 mmol/L, Alb < 30 g/L, CHO < 1.6 mmol/L, PLT < 5 x 10(9)/L, and higher HBV DNA loads (HBV DNA > 3 x 10(4) copies/ml in HBeAg negative patients and > 1 x 10(5) copies/ml in HBeAg positive patients) were shown to be associated with a poor prognosis. Coefficients of regression of the above factors were 1.539, 21.356, 1.398, 1.650, 2.440, 2.266, 1.738, 2.631 and 2.656 respectively. The coefficients of regression of HBV DNA loads were: B = 2.656, Wald = 7.768, P = 0.005, EXP(B) = 14.235, and 95.0% CI for EXP(B) = 2.199-92.133.</p><p><b>CONCLUSIONS</b>Our results indicate that the HBV DNA loads were one of the most important factors influencing the prognosis of the chronic severe hepatitis B patients, the importance is only next to hepatorenal syndrome and over grade II hepatic encephalopathy. HBeAg positivity/negativity has no influence on the prognosis, but HBV DNA loads are important; the lower the viral loads, the better the prognosis.</p>

The factors associated with viral relapse after interferon treatment in chronic hepatitis C patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between hepatitis C virus (HCV) genotype, serum viral load and ALT levels, and the factors associated with the viral relapse after IFN treatment in patients with chronic hepatitis C.</p><p><b>METHODS</b>The HCV RNA levels were determined with Cobas Amplicor Monitor Test, version 2.0, and HCV genotypes were examined by means of PCR products of 5' NTR digested with restriction endonucleases. The patients with chronic hepatitis C were treated with PEG-IFN alpha -2a and Roferon-A for 24 weeks. Those with a viral response after 24 week treatment were followed for an additional 24 weeks. The association of clinical characteristics, such as sex, age, the way of the HCV infection, IFN treatment history and platelet counts, and the HCV genotype, virus load and medicine used for the viral relapse after IFN treatment were analyzed.</p><p><b>RESULTS</b>Of the 208 chronic hepatitis C patients, the ALT levels were not related to HCV RNA levels (r = 0.093, P > 0.05). No difference of ALT levels between HCV genotypes was found, and the HCV RNA load was also of no difference between HCV genotype 1 patients and non 1 patients. Of the 119 patients with viral response after 24 week treatment, 58 cases (48.7%) relapsed after another 24 week's follow-up. Relapse was not significantly related to the clinical characteristics, such as sex, age, mode of the infection, treatment history of IFN, AST/ALT ratio, platelet counts and the baseline viral load. Among patients with genotype 1 virus, the relapse rate was significantly higher than those patients with non-genotype 1 virus (54.5% vs 32.1%, P=0.039). The relapse rate after PEG-IFN alpha -2a treatment was lower than that of Roferon-A treatment (47.0% vs. 52.8%), but not significantly.</p><p><b>CONCLUSION</b>The viral relapse of chronic hepatitis C patients after IFN treatment was significantly associated with the genotypes of the HCV.</p>

Retreatment with interferon of relapsed chronic hepatitis C patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and investigate the influencing factors of the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed after a previous IFN treatment.</p><p><b>METHODS</b>A retrospective study was designed to analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All patients were from a randomized, opened and multi-center clinical trial about the efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the treatment of chronic hepatitis C in China. There were 35 patients treated with PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the efficacy was sustained viral response (SVR) rate. The influence of viral concentration in serum, genotype and drug categories on the responses to IFN were analyzed.</p><p><b>RESULTS</b>For all the patients, the end of treatment virus response (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG-IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00% respectively, P < 0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher than that of CIFNalpha-2a (45.71% and 20.00% respectively, P < 0.05). However, there was no significant difference between the high and low viral load groups. Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%, 11.11%), (P < 0.01, P < 0.05 respectively), but in patients with genotype non-1, there were no such differences between the two groups.</p><p><b>CONCLUSION</b>Some relapsed patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha-2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be used in the relapsed cases with genotype 1. The viral load was not associated with the efficacy of IFN retreatment.</p>

Immune response for phase I clinical trial of a hepatitis B immunogenic complex therapeutic vaccine, YIC / 中华肝脏病杂志

<p><b>OBJECTIVE</b>A hepatitis B immunogenic complex therapeutic vaccine, yeast-derived recombinant HBsAg combined with human anti-HBs immunoglobulin (YIC), was evaluated for safety and immune response in phase I clinical trial.</p><p><b>METHODS</b>The subtypes IgG1, IgG2, IgG3 and IgG4 of serum anti-HBs collected from 20 immunized subjects were analyzed by ELISA. The lymphocyte proliferation assay was carried out in five subjects and was analyzed by 3H-thymidine incorporation. The assays for IFNgamma, IL-2, IL-4, IL-6, IL-10 and TNFalpha were measured using Human Cytometric Bead Array Kit with FACSCalibur.</p><p><b>RESULTS</b>The results showed that the subtypes of anti-HBs antibodies induced by 30, 60 and 90 microg YIC-immunized groups among all of the adult volunteers (20/20) were IgG1 and IgG3. The level of IgG1 was higher than that of IgG3 in each volunteer but the strength was different from each other. The rHBsAg-stimulated lymphocyte proliferation induced by three injections of 90 microg of YIC showed that the stimulation index was more than 2.0 in four out of the five individuals (4/5), ranging from 2.70 to 4.75. PHA-stimulated lymphocyte proliferation was not related to rHBsAg-stimulated lymphocyte proliferation. In the 60 microg YIC-immunized group there was no significant difference between the levels of IFNgamma, IL-2, IL-4, IL-6 and IL-10 at day 0 and day 42. At day 71, in comparison to day 0, the level of IFNgamma was higher in all eight subjects studied (P = 0.015) and the level of IL-2 was also increased in seven out of eight subjects (P = 0.002). In contrast, the levels of IL-4, IL-6, IL-10 and TNFalpha showed no significant difference in all the subjects (P-values: 0.298, 0.976, 0.202 and 0.996).</p><p><b>CONCLUSION</b>Our results indicate that this hepatitis B immunogenic complex therapeutic vaccine (YIC) can induce a potent anti-HBs response.</p>

Use of direct portal vein puncture portography with modified TIPS treatment in patients with portal hypertension and gastro-esophageal varices bleeding / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore a better procedure for transjugular intrahepatic portosystemic shunt (TIPS) in order to improve its safety and to extend its indications.</p><p><b>METHODS</b>To puncture the right portal branch under sonographic guidance in 20 patients with portal hypertension and gastro-esophageal bleeding. The Teflon sheath with gold marker was put into the portal vein; anterior and lateral portography was made, portal pressure was measured and the gastric coronal vein was embolized. The gold marker was put into the portal vein puncture site and the Rups-100 was guided under the gold marker during the TIPS puncture procedure. Anterior and lateral portography was again made to make sure the puncture site was 2 cm away from the portal vein bifurcation. In some cases a 10F sheath was used to suck the thrombosis in the portal vein, and a balloon was used to dilate the parenchyma channel and then a stent was released smoothly.</p><p><b>RESULTS</b>20 reformed TIPS were successfully performed on all patients and their gastric-esophageal bleedings were controlled immediately. 37 punctures were made in 20 of those cases; the average puncture per patient was 1.85+/-0.67, lower than that of the traditional method. The pressure of the portal vein declined from (30.5+/-1.1) mmHg to (16.9+/-0.9) mmHg, P < 0.05, showing that the difference of portal vein pressure before and after the reformed TIPS was significant. 25 stents were placed, and no complications occurred during the procedure in any of the cases.</p><p><b>CONCLUSION</b>Direct portal vein puncture portography and gold marker guided TIPS procedure is feasible and safe; the indications of TIPS could be further extended.</p>