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.

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.

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 .

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.

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 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 study the role of inositol requiring enzyme 1 (IRE1)-mediated endoplasmic reticulum stress on hepatocyte apoptosis of experimental fulminant hepatic failure (FHF).Methods Thirty male depuratory Wistar rats were manufactured to be FHF model by peritoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS),and 30 rats were injected peritoneally with 0.9％ sodium chloride solution as controls.The apoptosis of liver cells was detected by flow cytometry.The protein and mRNA expressions of Caspase-12 and IRE1 in liver tissues were detected by immunohistochemistry and reverse transcriptation-polymerase chain reaction (RT-PCR).The independent samples were compared by Kruskal-Wallis H test.The comparison between two groups at the same time point was done by Mann-Whitney U test.The correlation analysis was done by rank correlation.Results The apoptotic rates of liver cells at 2,4,8 and 12 hours were increased over time in model group (x2 =25.475,P=0.01),which were higher than control group (U=0,P＜0.01).The expressions of Caspase-12 and IRE1 proteins in liver tissues were upregulated in model group,while the expressions were not detected in control group.The expressions of Caspase-12 and IRE1 mRNA in model group were also increased over time and peaked at 8 h,then gradually decreased; the differences among different time points were statistically significant (x2 =23.983,x2 =24.820; both P＜0.01),and all higher than control group (U=0,P＜0.01).IRE1 was positively correlated with both Caspase-12 and hepatocellular apoptotic rate (r=0.733 and 0.715,respectively;both P＜0.01).Caspase-12 was positively correlated with hepatocellular apoptotic rate (r=0.586,P＜0.01).Conclusions IRE1 mediated endoplasmic reticulum stress on hepatocyte apoptosis is closely related to the development of FHF.The earlier intervention on endoplasmic reticulum stress pathway,the more protective effect in liver failure.

Objective To investigate the expression and significance of adiponectin(Adip) and the it's receptor 1, 2( AdipoR1, AdipoR2) in the pathogenesis of alcoholic liver disease ( ALD). Methods Fifty male Wistar rats were acclimatized for 7 days and then 10 rats were randomly assigned to be control. Others were to develop the rats mod-el of ALD by intragastric alcohol of increasing concentration and volume gradually [30% ～ 60%, 5 ～9 g/(kg · d)] , 8, 8, 8 and 9 rats were sacrificed randomly at the end of 4th, 8th, 12th and 16th week, liver samples and liver homogenate (10% ) were collected respectively. The concentration of triglyceride (TG) in the liver homogenate and the level of adiponectin and tumor necrosis alpha (TNFα) in the serum were measured by bi-ochemical chromatometry and ELISA method respectively. The mRNA and protein expression of Adip, AdipoRl and AdipoR2 in the hepatic tissue were performed by reverse transcription polymerase (RT-PCR) and Western blot. Results The model of rats alchoholic liver disease was developed. With the progress of ALD,the level of TG and TNFα in serum increased and the contention of Adip decreased gradually. The expression of Adip and AdipoR2 mRNA and protein decreased and no significant change was found in the AdipoRl. There is a negative correlationbetween the expression of serum Adip and AdipoR2 in hepatic tissue and the level of serum TNF-α and TG in the liver homogenate. ( r =-0. 98 ～-0. 90, P < 0. 01 ). The expression level of Adip protein was positively correlated with the contents of Adip in the serum ( r = 0. 90, P < 0. 01 ). Conclusion There is a close correlation between the decreased expression of Adip and AdipoR2 and adipose degenaration and inflammation in hepatic tissue.