Study on F9 gene expression downregulation and its clinical value in hepatocellular carcinoma / 中华肝脏病杂志

Objective: To analyze the expression levels of the F9 gene and F9 protein in hepatocellular carcinoma by combining multiple gene chip data, real-time fluorescence quantitative PCR (RT qPCR), and immunohistochemistry. Additionally, explore their correlation with the occurrence and development of hepatocellular carcinoma, as well as with various clinical indicators and prognosis. Methods: The mRNA microarray dataset from the GEO database was analyzed to identify the F9 gene with significant expression differences associated with hepatocellular carcinoma. Liver cancer and adjacent tissues were collected from 18 cases of hepatocellular carcinoma. RT-qPCR method was used to detect the F9 gene expression level. Immunohistochemistry was used to detect the F9 protein level. Combined with the TCGA database information, the correlation between F9 gene expression level and prognostic and clinicopathological parameters was analyzed. The biological function of F9 co-expressed genes associated with hepatocellular carcinoma was analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Statistical analysis was performed using Graphpad Prism software. Results: Meta-analysis results showed that the expression of the F9 gene was lower in HCC tissues than in non-cancerous tissues. Immunohistochemistry results were basically consistent with those of RT-qPCR. The data obtained from TCGA showed that the F9 gene had lower expression values in stages III-IV, T3-T4, and patients with vascular invasion. A total of 127 genes were selected for bioinformatics analysis as co-expressed genes of F9, which were highly enriched in redox processes and metabolic pathways. Conclusion: This study validates that the F9 gene and F9 protein are lower in HCC. The down-regulation of the F9 gene predicts adverse outcomes, which may provide a new therapeutic target for HCC.

The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection / 中华肝脏病杂志

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

Unsatisfying antiviral therapeutic effect in patients with mother-tochild transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study / 中华医学杂志(英文版)

Background@#Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group.@*Methods@#The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected.@*Results@#Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ2 = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response.@*Conclusion@#Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission.@*Trial Registration@#NCT01962155; https://clinicaltrials.gov.

Unsatisfying antiviral therapeutic effect in patients with mother-to-child transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study / 中华医学杂志(英文版)

BACKGROUND@#Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group.@*METHODS@#The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected.@*RESULTS@#Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response.@*CONCLUSION@#Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission.@*TRIAL REGISTRATION@#NCT01962155; https://clinicaltrials.gov.

Research progress of the natural small molecular products synergistically with antifungal agents to inhibit drug-resistant fungi / 药学学报

The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.

Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans / 药学学报

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

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>

Investigation of entecavir treatment in patients with LAM-refractory chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB).</p><p><b>METHODS</b>In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles.</p><p><b>RESULTS</b>At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion.</p><p><b>CONCLUSION</b>While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.</p>

High serum interleukin-6 level is associated with increased risk of delirium in elderly patients after noncardiac surgery: a prospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between inflammation and delirium remains to be determined. The purposes of this study were to investigate the association between serum interleukin-6 levels and the occurrence of delirium in elderly patients after major noncardiac surgery.</p><p><b>METHODS</b>A total of 338 elderly patients (60 years of age and over) undergoing major noncardiac surgery were enrolled. Blood samples were obtained before anesthesia and in the first postoperative morning and serum interleukin-6 concentrations were measured. Delirium was assessed twice daily by the confusion assessment method for the Intensive Care Unit during the first three postoperative days. Survival analyses were performed to assess the relationship between the serum IL-6 level and the occurrence of postoperative delirium.</p><p><b>RESULTS</b>Postoperative delirium occurred in 14.8% (50 of 338) of patients. High serum interleukin-6 levelsafter surgery were significantly associated with increased risk of the occurrence of postoperative delirium (hazard ratio 1.514, 95% confidence interval 1.155-1.985, P = 0.003). Other independent predictors of delirium included increasing age, poor preoperative New York Heart Association classification, low preoperative Mini-Mental State Examination score, and high total postoperative Visual Analogue Scale pain score. Patients who developed delirium had a prolonged hospital stay after surgery.</p><p><b>CONCLUSIONS</b>Delirium is a frequent complication in elderly patients after noncardiac surgery. High serum interleukin-6 level after surgery is associated with increased risk of the occurrence of postoperative delirium.</p>

Clinical observations of sequential interferon therapy following complete response to telbivudine treatment in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic benefit of sequential interferon alpha-1b (IFNa-1b) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who showed early complete response to telbivudine (LdT) treatment, and to explore the clinical value of serum hepatitis B surface antigen (HBsAg) for predicting sustained virological response (SVR).</p><p><b>METHODS</b>Twenty HBeAg+ CHB patients who had shown a complete response to LdT therapy before treatment week 52 were divided into two treatment groups: one continued on the LdT treatment for an additional 6 months, and the other switched to IFNa-1b for 6 months. Each patient presented for follow-up examinations at 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36 months after treatment cessation. Serum levels of alanine aminotransferase (ALT) and creatinine were detected by an automated biochemical analyzer. HBV DNA load was determined by real-time PCR. HBsAg and HBeAg levels were assessed by chemiluminescence.</p><p><b>RESULTS</b>The relapse rate was lower in the group treated with sequential IFN than in the group who continued LdT treatment (30% vs. 40%, P more than 0.05). The area under the receiver operating characteristic curve at week 24 (0.689) was significantly higher than at week 12 and week 48 (0.652 vs. 0.545, P less than 0.05). Decline in serum HBsAg levels at week 24 were predictive of SVR after treatment cessation. Patients showing a decrease more than 1000 IU/ml in serum HBsAg levels at week 24 had a significantly higher SVR rate than the patients who showed a decrease less than 1000 IU/ ml (90.9%(10/11) vs. 33.3%(3/9), P less than 0.05). At the end of treatment, patients showing a decrease less than 200 IU/ml of serum HBsAg levels had a significantly higher SVR rate than those showing more than 200 IU/ml (100% vs. 53.3%, P less than 0.05).</p><p><b>CONCLUSION</b>Sequential IFNa-1b consolidation therapy does not reduce the rate of relapse after treatment cessation. However, patients with a decrease in serum HBsAg levels of more than 1000 IU/ml at treatment week 24 are more likely to achieve SVR.</p>

Efficacy and safety of a protease inhibitor with pegylated interferon and ribavirin in patients with untreated chronic hepatitis C: a meta analysis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of a double therapy containing pegylated interferon and ribavirin to a triple therapy (with addition of a protease inhibitor) for untreated chronic hepatitis C with genotype 1 infection.</p><p><b>METHODS</b>We searched Pub med, EMBASE, OVID, the Cochrane Library Clinical Trials Registry and included relevant randomized controlled trials for comparing the efficacy and safety of the triple therapy to the double therapy in HCV genotype 1 untreated patient, using terms: protease inhibitor, hepatitis C, genotype 1. The primary endpoints were composed of the rates of SVR, the rates of relapse, the rates of anemia, and the rates of discontinuation due to severe adverse events, respectively.</p><p><b>RESULTS</b>Five trials (involving a total of 3200 patients) were included. Data showed the triple therapy with either telaprevir or boceprevir significantly increased the SVR rate and decreased the relapse rate compared with the double therapy [for SVR rate, 65.4% vs. 40.9%, OR=2.92, 95% CI 2.5 to 3.42, P less than 0.01, and for relapse rate, 11.3% vs. 24.8%, OR=0.42, 95% CI 0.26 to 0.68, P less than 0.01], but the triple therapy associated with higher side effects and intolerability [ higher anemia rate, 44.1 % vs. 26.2%, OR=2.25, 95% CI 1.9 to 2.65, P less than 0.01 and higher discontinuation rate owing to severe adverse events, 12.4% vs. 7.7%, OR=1.66, 95% CI 1.19 to 2.32, P less than 0.01]. Subgroup analysis found that the rates of SVR were still higher and the relapse rates were lower in all triple treatment groups [composed by 24 (or 28) -week groups, 48-week groups, and response-guided therapy groups] than that of the double therapy.</p><p><b>CONCLUSION</b>A triple therapy with peginterferon-ribavirin plus either boceprevir or telaprevir significantly increased the rate of sustained virologic response among untreated patients infected with hepatitis C genotype 1. Both the incidence of adverse events and the frequency of discontinuation owing to severe adverse events were higher in patients receiving the triple therapy than those receiving the standard double therapy.</p>

Comparison of peg-interferon monotherapy to peg-interferon and nucleoside analogue combination therapy for hepatitis B: a meta-analysis of randomized controlled trials / 中华肝脏病杂志

To evaluate the efficacy and safety of pegylated-interferon (Peg-IFN) treatment as monotherapy or in combination with nucleoside analogues (NAs) for treating chronic hepatis B (CHB) infection.Searches of PubMed, OVID, EMBASE, and the Chinese Medical (WanFang, CNKI, and VIP) databases were conducted to identify all relevant randomized controlled trials published since January 1990. Twelve studies comparing Peg-IFN monotherapy to NA combination therapy (lamivudine (LAM), n =8); adefovir (ADV), n = 4) met the inclusion criteria (treatment duration, range: 48-52 weeks; follow-up, range: 24 weeks to three years). Meta-analysis was performed with RevMan 5.0 using the fixed-effects and random-effects models. Patients who had received combination therapy had a higher biochemical response rate at the end of treatment than those who had received monotherapy (51.1% vs. 38.9%, odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.33-2.01, P less than 0.01). Subgroup analysis of Peg-IFN combination therapies with LAM or ADV indicated that neither NA type significantly enhanced the increased efficacy of combination therapy compared to monotherapy. The combination therapy subgroups also had higher virologic response rates at the end of treatment than the monotherapy subgroups (LAM: 65.9% vs. 34.9%, OR = 3.57, 95% CI: 1.83-6.95, P less than 0.01; ADV: 74.6% vs. 46.2%, OR = 3.66, 95% CI: 2.13-6.30, P less than 0.01). Moreover, the combination therapy group had a higher sustained biochemical response rate at the end of follow-up than the monotherapy group (47.6% vs. 42.1%, OR = 1.28, 95% CI: 1.05-1.55, P less than 0.05). The LAM combination therapy subgroup had a significantly higher biochemical response rate than the monotherapy subgroup, but there was no significant difference between the LAM and ADV combination therapy subgroups. At the end of follow-up, the ADV combination therapy subgroup had a significantly lower rate of hepatitis B e antigen (HBeAg) than the monotherapy subgroup, but there was no significant difference between the ADV and LAM combination therapy subgroups for HbeAg reduction. The combination therapy group and monotherapy group showed no statistically significant differences in HBsAg reduction or occurrence of severe adverse events. Peg-IFN/NA combination therapy produces a higher biochemical response rate in CHB patients than PEG-IFN monotherapy. Moreover, Peg-IFN/ADV combination therapy produces a greater reduction in HBeAg than Peg-IFN monotherapy.

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>

Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: a meta-analysis

Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus [HCV] infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes. To assess the associations of single nucleotide polymorphisms [SNP] of the IL28B and sustained virologic response [SVR] of patients with chronic hepatitis C to PEG-interferon/ ribavirin therapy. We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate of SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied. The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans [OR =3.85, 95% CI:3.06-4.83]; the percentage of rs12979860 TT genotype was lower in Caucasians than that of Afro-Americans [OR=3.45, 95% CI=2.68-4.44]. Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 [OR=0.16, 95%CI: 0.11-0.24]. IL28B is significantly associated with response of PEG-interferon/ ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes

Comparison of the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients.</p><p><b>METHODS</b>In this open-label study we randomly assigned 125 CHB patients to receive 0.5 mg of entecavir (n = 56) or 10mg of adefovir (n = 69) once daily for 48 weeks.</p><p><b>RESULTS</b>HBV DNA, ALT and HBeAg were quantified at baseline and at 0, 24, 48 weeks. At week 24 and 48, more patients in entecavir group than in adefovir group achieved undetectable serum HBV DNA level (68% vs 35%, 84% vs 49%, P < 0.05). The percentage of patients with normal ALT level in the two groups at week 48 was similar (100% vs 94%, P > 0.05). Among the HBeAg positive patients, more patients in entecavir group than in adefovir group had HBeAg loss at week 24 and 48 (23% vs 7%, 44% vs 15%, P < 0.05). The ratio of HBeAg seroconversion was similar in the two groups at week 24 (18% vs 7%, P > 0.05), but more patients in entecavir group than in adefovir group achieved HBeAg seroconversion at week 48 (33% vs 12%, P < 0.05). The retreated patients in the entecavir group had a higher chance to achieve undetectable serum HBV DNA level (79% vs 34%, P < 0.05), HBeAg loss (42% vs 17%, P > 0.05), and seroconversion (26% vs 17%, P > 0.05), than these in the adefovir group. The safety profiles and adverse event profiles were similar in the two groups.</p><p><b>CONCLUSIONS</b>Compared to adefovir, entecavir is more potent to suppress HBV replication.</p>

Dynamic changes of Th1/Th2 type cytokines in peripheral blood of patients with hepatitis B e antigen-positive chronic hepatitis B treated with telbivudine / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of Th1/Th2 type cytokines in peripheral blood of patients with hepatitis B e antigen-positive chronic hepatitis B treated with telbivudine (LDT).</p><p><b>METHODS</b>The levels of IL-2, IL-4, IL-6, IL-10, TNF alpha, IFN gamma in the blood cells of HBeAg positive chronic hepatitis B patients were measured at 0, 4, 8, 12, 24, 48 weeks after LDT treatment by fluorescence activated cell sorting (FACS), the levels and dynamic changes of Th1/Th2 type cytokines in groups of complete response, partial response, non-response, virologic breakthrough were compared.</p><p><b>RESULTS</b>The levels of Th1 type cytokines in complete response group were higher than those in groups of partial response, non-response and virologic breakthrough, however, the levels of Th2 type cytokines showed an opposite trend compared with Th1 type cytokines. There were no significant differences between each group. In complete response group, the levels of IL-2, TNF alpha and IFN gamma were higher than baseline 12 weeks after LDT treatment (P < 0.05). In partial response group the level of IFN gamma was higher than baseline 24 weeks after LDT treatment (P < 0.05). In non-response group, the levels of IL-6 and IL-10 were higher than baseline at 48 weeks after LDT treatment (P < 0.05). In virologic breakthrough group, the level of IL-4 was higher than baseline 24 weeks after LDT treatment (P < 0.05), while the level of IL-6 was higher than baseline 12 weeks after LDT treatment (P < 0.05).</p><p><b>CONCLUSIONS</b>The balance of Th1/Th2 type cytokines plays an important role in the outcome of patients with hepatitis B e antigen-positive chronic hepatitis B treated with LDT. The immune response of patients with chronic hepatitis B is improved to some extent after LDT therapy.</p>

Nucleos(t)ides as prophylaxis for the reactivation of hepatitis B virus in immunosuppressed patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation.</p><p><b>METHODS</b>Non-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated.</p><p><b>RESULTS</b>Of the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation.</p><p><b>CONCLUSION</b>HBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.</p>

Analysis of spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks.</p><p><b>METHODS</b>Chronic hepatitis B patients not receiving antiviral treatment from 2003 to 2005 were divided into two groups according to the baseline value of ALT and TBil. Spontaneous decline of HBV DNA were retrospected, and the influence of the baseline value of ALT and TBil on spontaneous decline of HBV DNA was analyzed.</p><p><b>RESULTS</b>Total of 213 chronic hepatitis B patients (male 174, female 39, aged from 18 to 65) were recruited in this study, including 124 mild and moderate type of hepatitis B, 89 severe type of hepatitis B, and 19 patients (8.92%) were lost at the end of the 12th week. The mean baseline value of HBV DNA of all the patients was (6.66+/-1.03) log10 copies/ml, at 12 week the mean value of HBV DNA of all the patients was (5.98+/-1.53) log10 copies/ml (compared to baseline P<0.01), the decline value of HBV DNA was (0.68+/-1.46) log10 copies/ml. The mean baseline value of HBV DNA of patients with the severe type of hepatitis B was lower than that with the mild or moderate type of hepatitis B patients [(6.45+/-0.99) log10 copies/ml and (6.81+/-1.04) log10 copies/ml respectively] (P<0.05). However, there was no significant difference in the mean and the declined value of HBV DNA between these two groups at the 12th week (P<0.05). At the 12th week, the baseline values of ALT and TBil were higher in patients with HBV DNA<or=3 log10 copies/ml than those in patients with HBV DNA>3 log10 copies/ml (P>0.05); And there were no significant difference in the baseline values of ALT and TBil between patients with the declined value of HBV DNA>or=2 log10 copies/ml and patients with declined value of HBV DNA less than 2 log10 copies/ml. At the 12th week, the mean and the declined value of HBV DNA were similar between the patients with ALT<or=5xULN and the patients with ALT>5xULN at baseline. The mean baseline value of HBV DNA of patients in the group of patients whose baseline value of ALT<or=5xULN while TBil<or=5xULN was higher than that in the group of patients whose baseline value of ALT>5xULN while TBil>5xULN, ALT<or=5xULN while TBil>5xULN, ALT>5xULN while TBil<or=5xULN (P<0.05 respectively), there were no significant difference in the rate of the HBV DNA<or=3 log10 copies/ml and the rate of the declining value of HBV DNA<or=2 log10 copies/ml between the groups at 12 week (P>0.05 respectively).</p><p><b>CONCLUSIONS</b>There is spontaneous decline of HBV DNA in patients with chronic hepatitis B in 12 weeks, but the level of liver injury is not correlated with the level of spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks.</p>

Five years trial of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of five-year trail of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area.</p><p><b>METHODS</b>32 patients failed with lamivudine therapy were enrolled in this study. In the double-blind phase, patients were randomly divided into entecavir 1.0 mg/d group (n = 28) and placebo group(n = 4) for 12 weeks. In the open-lable phase, patients received ETV 1.0 mg/d for 240 weeks. HBV DNA level, liver function, HBV serology were observed.</p><p><b>RESULTS</b>The mean reduction in HBV DNA level at week 12 was 4.05 log10 copies/ml in ETV group, and 0.08 log10 copies/ml in placebo group (P less than 0.05). The mean of HBV DNA level after 240 weeks of ETV treatment was decreased to 2.58 log10 copies/ml. The proportion of patients with HBV DNA less than 3 log10 copies/ml was 0, 6.25%, 15.6% , 50%, and 57.14% at 0, 8, 24, 96 and 240 weeks respectivfely. There were 2 patients with HBsAg seroconversion and 4 patients with HBeAg seroconversion at the end of the study. The ALT level returned to normal at week 12 and remained normal throughout the following 240 weeks. One patient had a severe adverse event during the trail.</p><p><b>CONCLUSION</b>Entecavir is effective and safe for the chronic hepatitis B patients failed with lamivudine therapy.</p>

Advances in the chemical and biological studies of polyamides / 药学学报

Polyamides, containing N-methylpyrrole (Py) and N-methyl-imidazole (Im) amino acids, are synthetic oligomers programmed to read the DNA double helix in the minor groove with high affinities and sequence specificities resulting in modulation of gene expression. They are cell permeable, stable and have no cytotoxicity, which provide a promising tool of gene regulation. We describe here recent advances in the field of DNA binding polyamides, including pairing rules, specifities and affinities to DNA, synthesis methods, cellular and nuclear uptake properties, gene regulation and effectiveness in vivo. The potential problems and difficulties in future research are also discussed.