Analysis of the correlation between the pre-S1 antigen, pre-S2 antigen and DNA of hepatitis B virus in the serum of chronic hepatitis B patients undergoing nucleoside analogue therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic correlation between pre-S1 antigen, pre-S2 antigen and HBV DNA in the serum of chronic hepatitis B (CHB) patients undergoing nucleoside analogue therapy.</p><p><b>METHODS</b>12 CHB patients with transient virological response after lamivudine treatment, and 20 patients treated with adefovir for 5 years were recruited in this study. Serum samples were collected at four time points when HBV DNA fluctuated sharply during lamivudine treatment, and at 0, 8, 12, 28, 52, 104, 156, 208, 260 weeks following adefovir treatment. HBV DNA was quantified by real-time PCR, pre-S1 and pre-S2 antigens were detected by ELISA.</p><p><b>RESULTS</b>The titers of pre-S1 and pre-S2 antigens were not correlated with the HBV DNA level in the serum of lamivudine treated patients. Only in one case of the adfovir treated patients, the decrease of pre-S1 and pre-S2 antigens was in parallel with the decrease of HBV DNA. Linear regression analysis indicated that neither pre-S1 antigen nor pre-S2 antigen was correlated with HBV DNA in the serum of lamivudine or adfovir treated patients (P more than 0.05).</p><p><b>CONCLUSION</b>Our results indicate that the titers of pre-S1 and pre-S2 antigens are not correlated with the serum HBV DNA in CHB patients undergoing nucleoside analogue therapy. Neither pre-S1 nor pre-S2 is a good predictor for the outcome of nucleoside analogue treatment.</p>

Increased expression of KCTD9, a novel potassium channel related gene, correlates with disease severity in patients with viral hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>Studies have shown that potassium channel plays a pivotal role in T cell activation. The expression of potassium channel gene KCTD9 was evidenced being highly upregulated in patients with severe hepatitis B (SHB). To understand this phenomenon further, tissue and cellular expression profiles of KCTD9 were investigated in patients with SHB.</p><p><b>METHODS</b>A rabbit peptide polyclonal antibody was prepared. Various samples including peripheral blood mononuclear cells (PBMCs); livers from patients with SHB or mild chronic hepatitis B, were examined for KCTD9 expression by quantitative real time PCR and immunohistochemistry staining (IHC). Confocal microscopy was used to illustrate the localizations of the expressions.</p><p><b>RESULTS</b>Increased expression of KCTD9 was observed in PBMC in over 35.7% of the patients with SHB when compared with that of patients with mild chronic hepatitis B. In all patients, the relative value of increased KCTD9 mRNA was positively correlated with alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin but negatively with serum albumin. The expression was mainly located in hepatocytes, bile duct epithelial cells, Kupffer cells and inflammatory cells, and in the cytoplasm of PBMCs from the healthy individuals and patients with mild chronic hepatitis B, whereas in both cytoplasm and nuclei in those from patients with SHB.</p><p><b>CONCLUSION</b>The increased expression of potassium channel gene KCTD9 correlates with disease severity in patients with viral hepatitis B.</p>

Distribution and characteristics of hepatitis B virus genotypes in Uighur patients with chronic hepatitis B in Xinjiang province of China / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study genotype distribution and the characteristics of hepatitis B virus (HBV) in Uighur patients with chronic hepatitis B (CHB) in Xinjiang, China.</p><p><b>METHODS</b>Type specific primers and PCR were used to detect the HBV genotypes of 127 Uighur CHB patients in Xinjiang. Genotyping results were confirmed by PCR product sequencing.</p><p><b>RESULTS</b>Among the 127 patients, the proportions of genotype D, B, C and B/D, C/D, B/C/D were 39.4% (50/127), 22.0% (28/127), 16.5% (21/127) and 9.4% (12/127), 8.7% (11/127) and 3.9% (5/127), respectively. The distribution of the HBV genotypes showed no significant differences between male and female patients (x2 = 8.058, P > 0.05), between HBeAg positive and negative patients (x2 = 6.033, P > 0.05), and between patients of different ages (x2 = 3.137, P > 0.05).</p><p><b>CONCLUSION</b>Genotype D HBV is predominant in Uighur patients with chronic hepatitis B in Xinjiang. The distribution of various HBV genotypes shows no significant differences between these Uighur patients with different HBeAg positivity, sex and age.</p>

A study on the situations of human L02 hepatocytes in genetically tolerized immunocompetent rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether human L02 hepatocytes could survive after implanting them into normal, immunocompetent rats.</p><p><b>METHODS</b>Human L02 hepatocytes were injected through the uterine walls into the intraperitoneal cavities of fetal Sprague-Dawley rats to induce immune tolerance to human L02 hepatocytes. Human L02 hepatocytes stained with DiI were implanted into the spleens of the 2-week old rats. Immuno-fluorescent staining, SP immunohistochemistry, and DiI staining were used to detect human albumin and specific proliferating cell nuclear antigen (PCNA) in the rat livers. The distribution of human L02 hepatocytes was observed under the fluorescent microscope.</p><p><b>RESULTS</b>Dynamic distribution of human L02 hepatocytes in the rat livers was observed from the 1st to the 10th week after the implantation. Human albumin was detected at 2, 4, 6 and 8 weeks, and at the 4th week it had the highest level. Specific human PCNA was detected in the rat livers from the 2nd to the 6th week after implantation. The PCNA positive cells were most abundant at the 4th week.</p><p><b>CONCLUSION</b>Human L02 hepatocytes can survive and proliferate for 10 weeks after implanting them into genetically normal immunocompetent rats.</p>

Study of the quasispecies dynamics of serum hepatitis B virus in a patient with acute exacerbations of chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the quasispecies dynamics of hepatitis B virus (HBV) during the course of exacerbation and resolution of chronic hepatitis B in a patients.</p><p><b>METHODS</b>Five serum samples were collected from a patient with two episodes of exacerbation and resolution of chronic hepatitis B. A method of PCR-TA cloning-conformation sensitive gel electrophoresis (CSGE)-sequencing was performed to study the dynamic changes of HBV quasispecies in basal core promoter (BCP), precore and core regions of HBV genome.</p><p><b>RESULTS</b>Quasispecies complexity was 10 and 12 at the points of exacerbations, and 14 and 17 at the points of resolutions (t = 3.133, P < 0.05). Ratio of dominant quasispecies in HBV population was high (42.4% and 51.5%) during exacerbations and low (30.3% and 21.2%) during resolutions (t = 3.295, P < 0.05). All dominant quasispecies, except the one during the second resolution, carried core P5T, L60V, S155T, and precore G1896A mutations.</p><p><b>CONCLUSION</b>The composition of HBV quasispecies changes due to the change of host immune status, and immune pressure might lead to the selection of immune escape mutants.</p>

Analysis of prognostic factors of and to establish a predictive model for patients with chronic severe hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze prognostic factors of and to develop a prognostic model for patients with chronic severe hepatitis (CSH).</p><p><b>METHODS</b>From December 1998 to October 2003, 385 in-patients being treated for chronic severe hepatitis were evaluated. The main clinical and laboratory variables were analyzed as predictive factors of survival with Cox univariate and multivariate regression models.</p><p><b>RESULTS</b>The median survival time of this study group was 47 days. The survival rates at 1, 3, 6 months, 1-year, and 3 years were 66.2%, 32.9%, 26.9%, 22.9% and 17.7% respectively. Four prognostic factors were extracted using Cox's proportional hazard model; the prognostic index (PI) was calculated using the following formula consisting of these factors. PI = 0.016loge + 1.148 hepatic encephalopathy + 0.294loge (bilirubin micromol/L) - 0.826loge (prothrombin time activity). The model accurately predicted 3 months survival in an independent series of 84 patients with chronic severe hepatitis.</p><p><b>CONCLUSION</b>The developed model is valuable in prognostic evaluation of chronic severe hepatitis and it may be useful to guide clinicians in selecting treatment methods for CSH.</p>