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>

Surveillance of Keshan disease in Wudalianchi city Heilongjiang province in 2009 / 中国地方病学杂志

Objective To analyze the surveillance results and grasp the situation of Keshan disease in Wudalianchi city Heilongjiang province.Methods In 2009,Kaifa village was selected as the surveillance point in Wudalianchi city,total resident population were monitored by routine clinical examination and 12-lead electrocardiogram(ECG) tracing.Suspected cases with Keshan disease were taken chest X-ray,and Keshan disease was diagnosed based on Keshan Disease Diagnostic Criteria (WS/T 210-2011).Results A total of 795 people were investigated,including 397 males and 398 females.Eighteen people were found to be the patients with Keshan disease,of which 13 cases were latent Keshan patients,5 cases were chronic Keshan patients.The overall detection rate was 2.27％,aged 24 to 83 years old.There was no acute type and subacute type of Keshan disease in the surveillance point.Twenty nine cases of abnormal ECG were detected,the detection rate was 3.65％ (29/795),of which the 18 patients with Keshan disease were all had abnormal ECGs,mainly taken the form of ST-T changes and completely right bundle branch blocked.Six cases of male patients with Keshan disease were detected,the detection rate was 1.52％ (6/397); 12 cases of female patients with Keshan disease were detected,the detection rate was 3.01％ (12/398).Conclusions There is still potential and chronic Keshan disease cases in Wudalianchi city.We must keep on the monitoring on Keshan disease,master the dynamical changes of the disease conditions,and carry out the targeted prevention and control of Keshan disease.

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>

A clinical study of N-acetylcysteine treatment in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of N-acetylcysteine (NAC) and glutathione (GSH) in treating chronic hepatitis B patients.</p><p><b>METHODS</b>Seventy-five patients with chronic hepatitis B were treated daily with an injection containing the same basic therapeutic drugs and randomly divided into a NAC group (50 patients) and a GSH group (25 patients). A daily dose of 8 grams of NAC and 1.2 grams of GSH was added to the injections of the two groups respectively. The trial lasted 28 days. Hepatic function and other biochemistry parameters (TBil, PTA, ALB et al) were tested on experimental day 0 and on days 7, 14, 21 and 28. The evaluation on the total effective rates of the NAC and GSH groups was based on the decreases of serum TBil and the increases of PTA.</p><p><b>RESULTS</b>Both NAC and GSH have therapeutic effects. The total effective rate was 84% in the NAC group and 72% in the GSH group. The rate of side effects was 13% in the NAC group.</p><p><b>CONCLUSION</b>NAC and GSH can decrease the level of serum TBil and increase PTA, but NAC was more effective in decreasing TBil than GSH. Serious adverse effects of NAC were not observed during the period of our treatment.</p>

Short-term results of telbivudine versus entecavir treatments in HBeAg-positive chronic hepatitis B patients in China / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of telbivudine (LDT) versus entecavir treatments in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Eighty HBeAg-positive compensated CHB patients with HBV DNA more than 6 log10 copies/ml and serum ALT 2 x ULN were divided into two groups: a telbivudine treatment group, and a entecavir treatment group. HBV DNA, ALT and HBeAg were surveyed at baseline and at 12 and 24 weeks. The efficacy and safety of the two nucleoside analogues were assessed at 12 and 24 weeks.</p><p><b>RESULTS</b>Undetectable serum HBV DNA levels of the telbivudine group (50% and 80%) were similar to those of the entecavir B group (50% and 70%) according to the polymerase-chain-reaction assay at week 12 and 24. There were no significant differences in the normalization of alanine aminotransferase levels between the two groups at week 12 and 24 (52.5% vs 60.0%, 77.5% vs 75.0%). The mean reductions in serum HBV DNA from the baseline levels at week 12 and 24 were similar between the two groups [5.27 vs.5.36, 6.49 vs.6.18 log (on a base-10 scale) copies per milliliter]. More patients in the telbivudine group had HBeAg seroconversion at week 12 than those in the entecavir group (20.0% vs 5.0%, P = 0.043); however, there was no significant difference between the two groups at week 24 (27.5% vs 17.5%). No adverse reactions were found in either group.</p><p><b>CONCLUSION</b>There was no significant difference in HBV DNA undetectable rates and the ALT normalization rates between the two groups in a short-term therapy (24 weeks), but the telbivudine group had a higher rate in HBeAg seroconversion than that in the entecavir group at week 12.</p>

Activation of extracellular signal-related kinases 1 and 2 in Sertoli cells in experimentally cryptorchid rhesus monkeys / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation.</p><p><b>METHODS</b>Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism.</p><p><b>RESULTS</b>The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 (CK18), a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2.</p><p><b>CONCLUSION</b>The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.</p>

Clinical investigation of famciclovir in chronic hepatitis B patients irresponsive to alpha interferon treatment / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To evaluate the efficacy and safety of famciclovir on the decreasing levels of serum HBV-DNA and ALT and HBeAg/antiHBe seroconversion in chronic hepatitis B patients irresponsive to 3 months treatment with alpha interferon.</p><p><b>METHODS</b>Two hundred and nineteen patients with chronic HBV infection, defined as positive HBsAg, HBeAg and HBV DNA, were enrolled and randomly half-and- half put into famciclovir and placebo groups. The two groups received either famciclovir 500 mg tid or a placebo treatment for 24 weeks, and then were followed-up for another 24 weeks with no treatment.</p><p><b>RESULTS</b>At the end of 24 weeks, the log value of HBV DNA dropped from 6.54+/-1.26 to 5.70+/-2.03 in the famciclovirt group and were elevated from 6.30+/-1.32 to 6.51+/-1.65 in the placebo group (P < 0.01). The rate of cases with persistence HBV DNA dropped 2 log of quantity in the famciclovir group and was 28.28% (28/99); it was 9.47% (9/95) in the placebo group (P < 0.01). Those with persistence negative HBV DNA was 28.28% (28/99) in the flamciclovir treated group and 14.74% (14/95) in the placebo group (P < 0.05). Those persistently being HBeAg negative were 7.69% (7/91) in the famciclovir treated group and 3.33% (3/90) in the placebo group (P > 0.05). The HBeAg/antiHBe seroconversion was 4.40% (4/91) in the famciclovir group and 2.22% (2/90) in the placebo group (P > 0.05). The percentage of cases with normal of ALT level was 15.15% in the famciclovir group and 6.35% in the placebo group (P < 0.05).</p><p><b>CONCLUSION</b>Famciclovir is effective in inhibiting HBV DNA replication and in decreasing serum ALT levels. The rate of HBeAg/antiHBe seroconversion in the famciclovir treated group was similar to that of the placebo group. Famciclovir was well tolerated without severe adverse effects during our treatment.</p>

A single factor analysis of the prognosis of 301 hepatitis failure cases and a study of a scoring system on their prognostic assessment / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To analyze the factors related to prognosis of hepatitis failure and to determine the factors which significantly affect it, and to build a scoring system for assessment of the prognosis of hepatitis failure and also to examine its efficacy for clinical use.</p><p><b>METHODS</b>Clinical data from 301 patients were analyzed retrospectively. The correlated degree between those single factors and prognosis of hepatitis failure was explored by logistic regression analysis. Independent risk factors of prognosis and those correlated coefficients, which were from logistic regression analysis, were used to build a scoring system. This system was used in analyzing the clinical data of 275 patients to examine its efficacy of the prognostic assessment.</p><p><b>RESULTS</b>The factors that significantly affected the prognosis of hepatitis failure included age, clinical typing, hepatic coma, total bilirubin, and others (P < 0.01). Some factors, including PTA, blood urea, sodium and hepatic coma, were independent risk factors of prognosis. The scoring system built gave different scores between the effective treatment group and ineffective treatment group with statistical significance (P < 0.01). When the score was less than 40, the probability of a recovery was 76.9%; when the score was 40 to 80, the probability of a recovery was only 12.5%. When the score was more than 80, the probability of a recovery dropped to 0%.</p><p><b>CONCLUSIONS</b>The factors, including PTA, blood urea and sodium and hepatic coma, are important in building a scoring system to assess the prognosis of hepatitis failure. The scoring system we built is very effective in evaluating the prognosis of hepatitis failure.</p>

A multi-center clinical study of N-acetylcysteine on chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To evaluate the effectiveness and safety of N-acetylcysteine (NAC) in treating chronic hepatitis B patients.</p><p><b>METHODS</b>144 patients with chronic hepatitis B (total bilirubin, TBil>170 mmol/L) from several centers were chosen for a randomized and double blind clinical trial. The patients were divided into a NAC group and a placebo group and all of them were treated with an injection containing the same standardized therapeutic drugs. A daily dose of 8 microgram NAC was added to the injection of the NAC group. The trial lasted 45 days. Hepatic function and other biochemistry parameters were checked at the experimental day 0 and days 15, 30, 45.</p><p><b>RESULTS</b>Each group consisted of 72 patients of similar demology and disease characteristics. During the trial, 28 cases of the 144 patients dropped out. In the NAC group, at day 0 and day 30, the TBil were 401.7 vs. 149.2 and 160.1+/-160.6. In the placebo group, the TBil on the corresponding days were 384.1+/-134.0 and 216.3+/-199.9. Its decrease in the NAC group was 62% and 42% in the placebo group. At day 0 and day 45 of treatment, the effective PTa increase rate was 72% in the NAC group and 54% in the placebo group. The total effective rate (TBil + PTa) was 90% in the NAC group and 69% in the placebo group. The parameters of the two groups showed a remarkable difference. The rate of side effects was 14% in the NAC and 5% in the placebo groups.</p><p><b>CONCLUSION</b>NAC can decrease the level of serum TBil, increase the PTa and reduce the time of hospitalization. NAC showed no serious adverse effects during the period of our treatment. We find that NCA is effective and secure in treating chronic hepatitis B patients.</p>

Neurogenesis of dentate granule cells following kainic acid induced seizures in immature rats / 中华儿科杂志

<p><b>OBJECTIVE</b>Data accumulated over the past years have led to widespread recognition that neurogenesis, the emergence of new neurons, persists in the hippocampal dentate gyrus of the adult mammalian brain, and can be increased by seizures in multiple models. Also, aberrant reorganization of dentate granule cell axons, the mossy fiber sprouting, occurs in human temporal lobe epilepsy and rodent epilepsy models. However a number of studies suggest that the immature brain is less vulnerable to the morphologic alteration of hippocampus after seizures. The goal of this study was to determine whether the seizures can induce dentate granule cell neurogenesis and mossy fiber sprouting in the immature rat.</p><p><b>METHODS</b>Seizures was elicited by unilateral microinfusion of kainic acid (KA, 1 micro g) into the amygdula at postnatal day 15 (P15). Rat pups were given bromodeoxyuridine (BrdU) intraperitoneally on day 5 after KA administration and killed 7 d or 21 d later. The brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using neuron-specific, early differentiation marker TuJ1 (betaIII tubulin) or granule-specific marker CaBP (calcium-binding protein calbindin D28k) as well as glia-specific marker GFAP (glial fibrillary acidic protein). Mossy fiber sprouting in intermolecular layer and CA3 subfield was assessed in Timm-stained sections both 1 month and 3 months after KA administration by using a rating scale and density measurement.</p><p><b>RESULTS</b>The dentate BrdU-immunoreactive cells of the KA-treated rats increased significantly compared with those of control rats on day 7 and 21 after BrdU administration (7 d: 244 +/- 15 vs. 190 +/- 10; 21 d: 218 +/- 19 vs. 133 +/- 12, P < 0.05). Approximately 80.2% and 78.7% of BrdU-labeled cells coexpressed TuJ1 in KA-treated rats and control rats on day 7 after BrdU respectively (P > 0.05). On 21 d after BrdU, 60.2% and 58.2% of dentate BrdU-labeled cells coexpressed GaBP in KA-treated rats and control rats respectively (P > 0.05). GFAP colocalized with 3%-5% dentate BrdU-labeled cells in the rats of both groups on day 7 and 21 after BrdU. It was also demonstrated that status epilepticus at P15 did not result in any detectable mossy fiber sprouting within the hippocampus both 1 month and 3 months after KA administration.</p><p><b>CONCLUSIONS</b>KA induced seizures can increase granule cell neurogenesis in the immature rat. Most of newly appeared cells migrate from subgranular proliferation zone (SGZ) into granule cell layer, the hilus as well as the molecular layer, and there they can differentiate into granule neurons. These observations also indicate that there is an early developmental resistance to seizure-induced mossy fiber sprouting in the immature brain.</p>

The effect of artificial support system on serum cytokine in chronic severe hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the changes of cytokines including TNFalpha, TGFbeta1 and nitrogen monoxide, and endotoxin in the serum of chronic severe hepatitis after the treatment of ALSS, and to evaluate further the value of ALSS in the treatment of chronic severe hepatitis.</p><p><b>METHODS</b>Forty two patients were screened. The changes of TNFalpha, TGFbeta1, nitrogen monoxide and endotoxin were detected respectively. The relationship between the cytokines and the severity and prognosis were further analyzed.</p><p><b>RESULTS</b>ALSS was effective to decrease the serum concentration of cytokines. TNFalpha dropped from (481.57+/-229.33) pg/ml to (156.46+/-78.12) pg/ml (P < 0.05). TGFbeta1 from (44.09+/-31.73) ng/ml to (27.77+/-23.28) ng/ml (P < 0.01), endotoxin from (1.05+/-0.37) Eu/ml to (0.28+/-0.22) Eu/ml (P < 0.001). NO from (71.15+/-33.09) micromol/L to (58.11+/-29.30) micromol/L (P < 0.001). Before the therapy endotoxin was related with TNFalpha and total bilirubin, while after the therapy, NO was related with protime and aminonemia.</p><p><b>CONCLUSION</b>High level of endotoxin and nitrogen monoxide in serum plays an important role in hepatocyte damage of chronic severe hepatitis. The changes of serum endotoxin TNFalpha, TGFbeta1 and nitrogen monoxide level in patients with chronic severe hepatitis can be used to judge the severity and prognosis of severe hepatitis. ALSS is a reliable hepatic support device for chronic severe hepatitis</p>

The difference between the positive rate of anti-HCV in the patients with severe viral hepatitis detected by the first generation or second generation enzyme linked-immunosorbent assay / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the positive rate of antibody to hepatitis C virus (anti-HCV) in sera of patients with severe viral hepatitis between 1984-1990 year and 1997-2003 year.</p><p><b>METHODS</b>Serum anti-HCV was detected by enzyme linked-immunosorbent assay (ELISA). It was detected by the first generation (1st) ELISA (Ortho Co. USA) in 79 cases of severe viral hepatitis during 1984-1990 year, and it was detected by the second generation (2nd) ELISA (Xiamen Xingchuang Co. China) in 251 cases of severe viral hepatitis during 1997-2003 year.</p><p><b>RESULTS</b>The positive rate of serum anti-HCV was 51.9% detected by the 1st ELISA in 79 cases of severe viral hepatitis during 1984-1990 year, and it was 1.2% detected by the 2nd ELISA in 251 cases of severe hepatitis during 1997-2003 year (chi2 = 133.68, P </= 0.001).</p><p><b>CONCLUSION</b>To compare with the positive rate of serum antibody to hepatitis C virus in severe viral hepatitis detected by the 1st ELISA, it was lower that detected by the 2nd ELISA</p>

Study on the replication of Hepatitis B Virus in primary hepatocytes from heterogenous species / 中华肝脏病杂志

<p><b>OBJECTIVES</b>By studying the possibility and degree of the replication and expression of human hepatitis B virus (HBV) genes in normal liver cells from heterogenous species, such as primary duck hepatocytes (PDH) and primary rat hepatocytes (PRH), to investigate the species-specificity of HBV infection and replication.</p><p><b>METHODS</b>PDH and PRH isolated by in situ perfusion with low concentration collagenase were transfected with complete HBV genome by electroporation (transfection group, about 1.19 10(12) copies of linear HBV DNA/1 10(7) PRH/PDH). From 1 day to 15 days after transfection, HBsAg and HBeAg in the supernatants and lysates of PRH/PDH were measured with IMX System, HBcAg was assayed with western blotting, Immunol dot blotting and Immunocytochemistry. Moreover, HBV S-mRNA and X-mRNA were tested with RT-PCR. Meanwhile, replicative intermediates of HBV DNA were analyzed by Southern blotting and Dot blotting. PRH/PDH electroporated only was used as control group.</p><p><b>RESULTS</b>HBsAg in the lysates of transfected PDH group were 15.24 (1day), 14.55 (3 days) and 5.13 ( 5 days; P/N values, positive>or=2.1), HBeAg all was negative (<2.1), and both were negative in the supernatants of transfected group. Viral antigen production in transfected rat hepatocytes: HBsAg in the lysates of transfected hepatocytes was positive, P/N values ranging from 2.17 to 93.41, The average P/N values was 14.74+/-31.82, and could be maintained for 15 days after transfection. Whereas, HBsAg in the supernatants of transfected group was only found positive on 1 day after transfection, which P/N value was 6.66. HBeAg and HBcAg in the lysates of PRH of transfection group were positive during the first 3 days following transfection, P/N values was around 2.8. The total amount of HBV DNA in the transfected PDH and PRH groups was strongly positive by dot blotting, whereas that of the control group was negative. Southern blot analysis of intracellular total HBV DNA indicated that there were relaxed circular (RC), covalently closed circular (ccc) and single-stranded (SS) HBV DNA replicative intermediates in the transfected PDH and PRH groups, there was no integrated HBV DNA in the cellular genome. Control groups were negative at all.</p><p><b>CONCLUSION</b>Expression of HBV genes and production can occur in hepatocytes from nonmammalian species or mammalian species, which strongly supports the idea that replication of HBV has no critical species-specificity, and yet it depends on the endoenvironment of hepatocyte.</p>

The efficacy of two type of membrane plasma separator on the treatment of patients with chronic severe hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>In order to compare the efficacy of two kinds of membrane plasma separator on the treatment of patients with severe hepatitis B.</p><p><b>METHODS</b>63 cases suffering from chronic severe hepatitis B were divided into two groups, 25 cases were treated with plasma exchange using Evacure-4A membrane plasma separator (A group) or 38 cases were using PS-06 membrane plasma separator (B group). Both of them also were treated with similar basic medical treatment. The level of serum total bilirubin, non-conjugated bilirubin, prothrombin time and albumin were tested at baseline and the end of the treatment with PE.</p><p><b>RESULTS</b>Evacure-4A and PS-06 membrane plasma separators can effientively remove bilirubin, the levels of serum total bilirubin, non-conjugated bilirubin of all patients were significantly decreased after treated with PE. In A group, the level of serum total bilirubin, non-conjugated bilirubin decreased from (464.2+/-193.8)micromol/L to (279.4+/-158.7)micromol/L, (293.5+/-129.1)micromol/L to (175.5+/-106.7)micromol/L (t=5.45, 10.36, P<0.01) respectively. In B group, the level of serum total bilirubin, non-conjugated bilirubin decreased from (493.2+/-126.9)micromol/L to (299.7+/-96.5)micromol/L, (300.2+/-74.3)micromol/L to (171.5+/-53.1)micromol/L (t=5.17, 12.04, P<0.01) respectively. The level of serum albumin increased after treated with PE in A and B groups, to contrast with PS-06, the increasing percentage of albumin was higher when the patients were treated with PE using Evacure-4A membrane plasma separator [(8.3+/-0.7) % vs. (3.4+/-9.3) %, t = 2.76, P<0.01].</p><p><b>CONCLUSION</b>Evacure-4A membrane plasma separator may be better than PS-06 membrane plasma separator on the treatment of patients with chronic severe hepatitis B.</p>

One year and half treatment with lamivudine in active cirrhosis resulting from chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the therapy effect of long term lamivudine treatment on active cirrhosis following chronic hepatitis B, and explore the methods for abnormalities resulting from lamivudine withdrawing.</p><p><b>METHODS</b>58 patients received lamivudine 100 mg orally everyday for 18 months. The changes were observed and wrote down, including clinical symptoms and signs, aminotransferase, virology indexes, and the abnormalities after lamivudine withdrawing, then further to find out plans for the latter.</p><p><b>RESULTS</b>(1) After lamivudine treatment, there were 35 patients whose situation stabilized, life quality improved, child-pugh score declined, and liver function turned better. (2) The level of HBV DNA decreased at least 10(3) copies/ml. HBeAg of 33.3% patients (13/39) became negative. (3) Among the 10 patients who stopped lamivudine of their own accord, and came again after 3 - 6 months because of hepatitis B recurring, two were treated with interferon for one month, then turning to liver-protecting methods for deteriorating, the other eight only received liver-protecting and immune-regulating treatment, whose liver function improved.</p><p><b>CONCLUSIONS</b>Long term treatment with lamivudine for active cirrhosis following chronic hepatitis B can improve liver function and life quality, prevent exacerbation. And it is not advisable to use interferon for hepatitis B relapsing after lamivudine withdrawing.</p>

Clinical research on the treatment effect of autologous dendritic cell vaccine on the patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the treatment effect of autologous HBsAg-loaded dendritic cells (DCs) on patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>Monocytes were isolated from fresh peripheral blood of 19 CHB patients by Ficoll-Hypaque density gradient centrifugating and cultured with plastic -adherence method. DCs were induced and proliferated from the monocytes with granulocyte-macrophage clony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for seven days. After being incubated with HBsAg for two hours, DCs were injected to patients subcutaneously twice at the interval of two weeks. HBV DNA level, alanine aminotransferase (ALT) level, and HBV markers in the serum of patients were tested every two months.</p><p><b>RESULTS</b>11 of the 19 (57.9%) patients responded to DC-treatment clinically. The rates of HBeAg clearance and HBeAg/anti-HBe seroconversion were 52.6% (10/19) and 26.3% (5/19) respectively, and the copies of HBV DNA decreased by 10(1.77 2.39) (t = 3.13, P < 0.01). Two patients who were treated in combination with lamivudine had complete clinical response. There was no difference in the trial effect between the DC treatment and the other two antiviral methods, and in the efficient rate between the patients whose ALT levels were high before treatment and those whose ALT levels were normal.</p><p><b>CONCLUSION</b>The autologous HBsAg-loaded DCs can effectively suppress HBV replication, reduce virus load in serum, eliminate HBeAg and promote HBeAg/ anti-HBe seroconversion. The patients whose ALT levels are high or normal can response clinically to DCs treatment. DCs in combination with lamivudine can eliminate virus more effectively.</p>

Long-term health-related quality of life in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate their long-term outcome and the efficacy and economic significance of antiviral drugs by investigating the long-term health-related quality of life (HQL) in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>The HQL of 101 CHB patients with biopsy-proven 6 to 18 years ago and 105 persons of general population as control was studied with revised SF-36 questionnaire.</p><p><b>RESULTS</b>The HQL in CHB patients was lower than that in general population in physical functioning, role physical, general health, mental health, and specific symptoms (mu > or = 2.10, P<0.05).</p><p><b>CONCLUSIONS</b>The long-term HQL in chronic hepatitis B patients is poor.</p>

An in vitro model of hepatitis B virus gene replication and expression in primary rat hepatocytes transfected with circular viral DNA / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish an in vitro model of hepatitis B virus (HBV) replication and expression in primary rat hepatocytes (PRH) transfected with circular viral DNA for further study on the interaction of HBV with hepatocytes.</p><p><b>METHODS</b>Circular viral DNA containing complete HBV genome were transfected into PRH by electroporation (transfected group, about 4mug of circular viral DNA/1 10(7)cells). From day 1 to day 10 after transfection, HBsAg and HBeAg in the supernatants and lysates of PRH were measured with IMX system. HBcAg was assayed with western blotting, immunol dot blotting and immunocytochemistry. Meanwhile, HBV S-mRNA and X-mRNA were tested with RT-PCR, and replicative intermediates of HBV DNA were analyzed by southern blotting and dot blotting. Moreover, Transmission electron microscopy was used if viral particles were produced in transfected rat hepatocytes. PRH electroporated only was used as control group.</p><p><b>RESULTS</b>(1) Viral antigen production in transfected rat hepatocytes: HBsAg in cell lysates was positive. P/N values ranged from 4.83 to 85.69, and could be maintained for 10 days after transfection. The average P/N values was 18.239 27.459. Whereas, HBsAg was negative in the supernatants of transfected group (P/N values, negative<2.1). HBeAg in the supernatants and lysates of transfected hepatocytes all was negative (P/N values<2.1) during 10 days following transfection. HBcAg was only found positive in transfected hepatocytes by immunol dot blotting. (2) Detection of viral transcripts: transcription of HBV DNA was investigated by preparing total RNA from rat hepatocytes 2 days after transfection and looking for S-mRNA and X-mRNA by RT-PCR. Results showed S-mRNA positive, X-mRNA negative. (3) HBV DNA replication analysis: intracellular total DNA was extracted 2 days after transfection and analysed by southern blotting. All replicative DNA intermediates, including relaxed circular (rcDNA), covalently closed circular (cccDNA), and single-stranded (ssDNA) linear HBV DNA forms, were indicated. Dot blotting showed intracellular HBV DNA positive in transfected group during 10 days after transfection. However, viral particles were not found in transfected hepatocytes during 3 days after transfection.</p><p><b>CONCLUSIONS</b>Circular HBV DNA transfected into primary adult rat hepatocytes could obtain continuous replication and stable expression of HBV surface antigen. This in vitro model has high reproducibility and stability, and is useful for directly studying the interaction of HBV with hepatocytes.</p>

A clinical research on oxymatrine for the treatment of chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of oxymatrine on chronic viral hepatitis B and to look for new methods for treating hepatitis B.</p><p><b>METHODS</b>Multi-center, controlled study was used. In this study, 196 patients were allocated to oxymatrine, oxymatrine with Ara-AMP, IFN-a1b, and glucose groups to observe ALT, AST and viral marker changes.</p><p><b>RESULTS</b>At the end of treatment, the rate of normal ALT, the negative rate of HBV DNA and HBeAg, and the positive rate of HBeAb were similar in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups. It was higher than that of glucose group. After 12 months follow up, the total effective rate is 40.8%, 60.8% and 43.1% in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups, respectively.</p><p><b>CONCLUSIONS</b>Oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b are effective to treat hepatitis B with a good negative rate of HBV DNA and HBeAg and positive rate of HBeAb.</p>

A study on the long-term outcome of hepatitis B e antigen-negative chronic hepatitis B compared with that of hepatitis B e antigen-positive chronic hepatitis B / 中华传染病杂志

0.05)between the two groups.Conclu- sion The long-term outcomes of e-CHB is not markedly different compared with that of e+CHB.