Positive serum hepatitis B surface antigen (HBsAg) is an indication of hepatitis B virus (HBV) infection,and the clearance of HBsAg usually stands for clinical cure of chronic hepatitis B (CHB).The clearance of HBsAg is influenced by the host,virus,antiviral drugs and other factors.This paper reviews the recent research progress on the related factors of HBsAg clearance in patients with CHB.

Objective To evaluate the efficacy of nucleos(t)ide analogues in patients with hepatitis B virus(HBV)-related chronic liver failure through Meta-analysis.Methods Literature search was done in Medline, PubMed, China National Knowledge Infrastracture(CNKI), Wanfang Database and China Biology Medicine(CBM)for papers published from 1990 to 2010 in Chinese or English, as well as the references in the relevant literature complemented by retrospective and manual literature search. Only literatures fully matching the inclusion and exclusion criteria could be included in this study. RavMan 5.0 statistical software was utilized for Meta-analysis. Then the sensitivity and publication bias about the data were measured by forest pl0t, funnel plot and fail-safe number. Results Total 1240 patients from 20 controlled clinical trials reported in Chinese and English papers were included in this study. The indicators of therapeutic efficacy were as below: HBV DNA undetectable rate relative risk(RR)=3. 37, 95％CI: 2. 20, 5. 16(Z=5. 60, P＜0. 01), prothrombin activity(PTA)weighted mean difference(WMD)=34.70, 95％CI: 25.62, 43.79(Z=7.49, P＜0.01), albumin(Alb)WMD=4.73, 95％ CI: 2.95, 6.51(Z=5.21, P＜0.01), alanine aminotransferase(ALT)WMD=42.58, 95％CI: -59.74, -25.41(Z=4.86, P＜0.01), total bilirubin(Tbil)WMD=-150.95, 95％CI: -199.29,-102.62(Z=6.12, P＜0.01), mortality RR=0. 55, 95％ CI: 0. 48, 0. 64(Z=8. 09, P＜0. 01). Conclusion Nucleos(t)ide analogues treatment could significantly increase HBV DNA undetectable rate, improve PTA and Alb, decrease levels of ALT and Tbil, which further reduces the short-term mortality of the patients with HBV-related chronic liver failure.

Objective To evaluate the clinical efficiency of glucocorticoids in treatment of severe hepatitis.Methods A systematic review on the efficacy of glucocorticoids in treatment of severe hepatitis was conducted.Relevant literatures were searched in PubMed (1966-2011),EMCC (1995-2011),Springer,CNKI,Wanfang Database and CBM.The retrieved literatures were screened according to the predefined inclusion and exclusion criteria.RevMan 5.0 statistical software was used for Meta-analysis.The mortality was evaluated by relative risk (RR),while the total bilirubin (TBil),ALT and prothrombin activity (PTA) were evaluated by weighted mean difference (WMD) and 95％ confidential interval (CI).The publication bias and sensitivity about the data were measured by forest plot and funnel plot.Results Twenty-three papers involving a total of 1457 patients were included in the study.Compared to control group,the mortality in glucocorticoids-treated group was lower (RR =0.39,95％ CI:0.32-0.47,Z =9.75,P＜0.01); and the TBil (WMD=-88.03,95％CI:-112.80-63.26,Z=6.97,P＜0.01),ALT (WMD=-25.04,95％CI:-42.23-7.84,Z=2.85,P＜0.01) and PTA levels (WMD=21.56,95％ CI:6.52-36.60,Z=2.81,P ＜0.01) in glucocorticoids-treated group were improved.Conclusion Glucocorticoids can effectively improve TBil,ALT and PTA levels,and reduce the mortality of patients with severe hepatitis.

MicroRNAs(miRNAs,miR) is a class of 21～22 nt small non-protein-coding single strand RNA molecules.In the liver,the phenotypic alternation or expressed abnormality of many miRNAs can influence the hepatitis virus replication at the gene level,which would provocate the development from hepatitis to hepatic fibrosis,cirrhosis,and even primary hepatic carcinoma on target.And so,several miRNAs are confirmed to be a new class of related gene to carcinoma.Furthermore,the dysfunction or abnormal quantity of miRNAs will promote the formation of fatty liver disease by interfering with signal transduction of insulin,inducing insulin resistance and then influencing normal metabolism of endosomatic lipid,Therefore,the specific medicine or methods,which might retrieve the expression or function of miRNAs in the hepatocytes,will provide a new valuable method to manage human liver disease.

Chronic HBV infection may not only cause liver damage , but also lead to renal injury . HBV-related kidney injuries mainly include ( 1 ) HBV-associated glomerulonephritis , ( 2 ) hepatorenal syndrome, and (3) kidney injuries caused by long-term nucleos(t)ide analogues therapy.This paper mainly reviews the pathogenesis and therapeutic principle of HBV-related kidney injuries , so as to provide the foundation for clinical management .

The activation of NK cell , mediated by natural killer group 2 ( NKG2 ) family receptor , plays an important role in antiviral immune response and disease progression after hepatitis B virus (HBV) infection.To explore the NKG2 receptors-mediated NK cell activation and its mechanism may be of value for anti-HBV targeting immune treatment .This article reviews the recent research progress on the role of NK cells and its NKG2 family receptors in immunity of chronic HBV infection and its mechanisms .

Objective To explore the expressions of adiponectin and adiponectin receptor 2 (AdipoR2) in the liver of patients with hepatitis B virus (HBV)-related liver failure and their clinical implications in the pathogenesis of liver failure.Methods The healthy controls (HC),patients with chronic hepatitis B (CHB) and patients with HBV-related liver failure (HBV-LF) were enrolled in the study.Each group had 20 participants.The liver tissues from 11 CHB patients who were diagnosed by liver biopsy,6 patients with HBV-LF and 6 liver donors during liver transplantation were collected.Histological specimens were observed by hematoxylin-eosin staining and Masson trichrome staining under microscope.The mRNA and protein expressions of adiponectin and AdipoR2 in the liver were measured by semi-quantitative reverse transcription and polymerase chain reaction (SqRT-PCR) and immunohistochemical staining,respectively.The level of serum adiponectin was detected by enzymelinked immunsorbent assay.Serum biochemical parameters and HBV DNA levels were also measured.The pairwise comparison between groups was done by Student-Newman-Keuls and mann whitney U test.The relationship between two variables was analyzed using Spearman correlation.Results The level of serum adiponectin in HBV-LF group [(0.86 ± 0.15) ng/mL] was higher than those in HC [(0.59±0.15) ng/mL] and CHB groups [(0.62±0.13) ng/mL,Z=3.963,Z=3.774,both P＜0.01)],but showing no difference between CHB and HC groups (P＞0.05).The expressions of adiponectin and AdipoR2 mRNA in the liver were significantly higher in HBV-LF group (0.251 ±0.028 and 0.223 ± 0.021,respectively) than those in HC (0.091 ± 0.018 and 0.072 ± 0.020,respectively) and CHB (0.121±0.019 and 0.097±0.017,respectively) groups (q=18.428,17.069,19.807,18.673,respectively; all P＜0.01).Also,the expressions of adiponectin and AdipoR2 mRNA in CHB group were significantly higher than those in HC group (q=3.895,3.860,both P＜0.05).The expressions of adiponectin and AdipoR2 proteins in the liver were significantly higher in HBV-LF group (8.482±0.772 and 7.654±0.272,respectively) than those in HC (4.045± 0.815 and 2.804±0.623,respectively) and CHB (5.545±0.613 and 4.775±0.458,respectively) groups (q=15.327,11.542; Z=2.802,3.266; respectively; all P＜0.01).Also,the expressions of adiponectin,AdipoR2 proteins in CHB group were significantly higher than those in HC group (q=5.894,Z=3.266,both P＜0.01).In HBV-LF group,serum adiponectin levels as well as the expressions of adiponectin mRNA and protein in the liver were negatively correlated with serum albumin (r=-0.815,-0.886,-0.943; P＜0.01 or P＜0.05),but positively correlated with serum alanine aminotransferase (r=0.701,0.886,0.943; P＜0.01 or P＜0.05).The expression of AdipoR2 mRNA in the liver was negatively correlated with serum albumin (r=-0.943,P＜0.01),but positively correlated with serum aspartate aminotransferase (r=0.829,P＜0.05).Conclusions The expressions of adiponectin and AdipoR2 are up-regulated during HBV infection,especially in patients with HBV-LF,which might reflect the degree of necroinflammation in the liver.

Objective To investigate the impact of tumor necrosis factor-α (TNF-α) on intestinal mucosa permeability and the protective effect of probiotics in mice with acute liver failure (ALF).Methods Thirty male BALB/c mice aged 6-8 weeks were randomly divided into normal control,ALF and intervention groups (10 for each group).Mice in intervention group were fed with live combined bifidobacterium and lactobacillus (900 mg · kg-1 · d-1) by gavage,while those in normal control and ALF groups were fed with normal saline (9 mL · kg-1 · d-1).After two weeks,mice in ALF and intervention groups were given an intraperitoneal injection of D-galactosamine (3.0 g/kg) to induce liver failure,and all mice were sacrificed 9 h after the injection.Biochemical markers were tested,expressions of TNF-α mRNA in liver tissues and zonula occluden-1 (ZO-1) mRNA in ileum tissues were detected by real-time PCR,and the expression of ZO-1 protein in ileum tissues was detected by Western blotting.One-way analysis of variance or Kraskal-Wallis test was performed to explore the differences in biochemical markers,TNF-α mRNA,ZO-1 mRNA and ZO-1 protein expressions among groups,and Pearson test was used to analyze the correlations between the expression of ZO-1 protein in ileum tissues and serum level of TNF-α or plasma levels of endotoxins.Results Serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),TNF-α and plasma level of endotoxins in ALF group were significantly higher than those in normal control group (P ＜0.01) ; while compared with ALF group,the above biomarkers were significantly decreased in the intervention group (P ＜ 0.01).The expression of TNF-α mRNA in liver tissues in ALF group was higher than that in the normal control group (Z =4.038,P ＜ 0.01) ; while compared with ALF group,it was decreased in intervention group (Z =3.780,P ＜ 0.01).The expressions of ZO-1 mRNA and ZO-1 protein in ileum tissues in ALF group were lower than those in normal control group (P ＜ 0.01) ; while compared with ALF group,those in intervention group were increased (P ＜ 0.01).Pearson analysis showed that the expression of ZO-1 protein in ileum tissues was negatively correlated with serum level of TNF-α level and plasma level of endotoxin (r =-0.946 and-0.919,both P ＜ 0.01).Conclusions TNF-α may be involved in the increased permeability of intestinal mucosa in mice with ALF.Live combined bifidobacterium and lactobacillus may relieve liver damages through inhibiting endotoxin synthesis and release,and ameliorate the permeability of intestinal mucosa through up-regulating ZO-1 protein expression.

Objective To investigate the association of SLC34A1 ( rs6420094 ) and RGS14 (rs4074995) polymorphisms with serum level of phosphorus in chronic hepatitis B virus (HBV) infection patients following long-term adefovir dipivoxil ( ADV ) treatment.Methods Ninety one patients with chronic HBV infections admitted in Third Hospital of Hebei Medical University during October 2012 and August 2013 were enrolled in the study.All patients received ADV treatment ( monotherapy or combination therapy) for at least two years, among whom 31 had hypophosphatemia and 60 had normal serum phosphorus levels.rs6420094 and rs4074995 were genotyped by polymerase chain reaction-restrictive fragment length polymorphism ( PCR-RFLP ) analysis.The relationship between allele frequency and serum phosphorus concentration was analyzed by Chi-Square test.Results In hypophosphatemia group, there were 13, 13, and 5 patients with genotype A/A, A/G and G/G at rs6420094, respectively;while in patients with normal serum phosphorus levels, there were 35, 24 and 1 patients with genotype A/A, A/G and G/G at rs6420094.The frequency of allele A at rs6420094 in patients with normal serum level of phosphorus was higher than that in hypophosphatemia group ( 78.3% vs.62.9%, χ2 =4.947, P <0.05 ).In hypophosphatemia group, there were 2, 11, and 18 patients with genotype A/A, A/G and G/G at rs4074995, respectively;while in patients with normal serum phosphorus level, there were 1, 21 and 38 patients with genotype A/A, A/G and G/G at rs6420094.There was no difference in the frequencies of alleles at rs4074995 between two groups (χ2 =0.625, P >0.05).Conclusion The polymorphism of rs6420094 gene may be associated with the serum level of phosphorus in patients with chronic HBV infections following long-term treatment of ADV.

Objective:To explore the effect of Toll like receptor 4(TLR4) and interleukin 1 belta,6,10 and tumor necrosis ? on the etiopathogenesis in rat model with alcoholic liver disease(ALD).Methods:A rat model of ALD was induced by intragastric alcohol.At the end of 4,8,12 and 16 weeks,liver and serum samples were collected.The levels of interleukin 1 belta,6,10 and tumor necrosis ? in serum were examined.Hematoxylin-eosin,sudan Ⅳ and sirius red staining were performed to obeserve the hepatic pathology.The mRNA expression of TLR4 in liver tissues were examined by reverse transcription polymerase chain raction(RT-PCR) method.Results:With the progress of ALD,the levels of interleukin 1 belta,6 and tumor necrosis ? in serum and the mRNA expression of TLR4 in liver tissues increased significantly(P