Hepatitis C ; metabolism ; Humans ; Vitamin D ; metabolism

Hepatitis ; metabolism ; pathology ; Humans ; Liver Regeneration

Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C.
Antiviral Agents/therapeutic use ; Chemokines/*metabolism ; Hepatitis C/drug therapy/*immunology/*metabolism ; Hepatitis C, Chronic/drug therapy/*immunology/*metabolism ; Humans

No abstract available.
DNA, Circular/*analysis ; Female ; Hepatitis B/*pathology ; Hepatitis B Surface Antigens/*genetics ; Hepatitis B virus/*metabolism ; Humans ; Male

Adult ; Female ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B, Chronic ; drug therapy ; immunology ; virology ; Humans ; Liver ; metabolism ; Male ; Middle Aged ; Vidarabine ; therapeutic use

OBJECTIVETo investigate the effect of miR-122 on the expression of hepatitis B virus (HBV) proteins.

METHODSAnti-sense oligodeoxynucleotide (ASODN) of two different sequences against miR-122, anti-miR-122 and LNA-antimiR-122 (Locked nucleic acid), human miR -122 (hsa-miR-122), or the negative control anti-GFP were designed and synthesized, then transfected into HepG2.2.15 cells. After 24 h and 48 h, the levels of HBsAg and HBeAg in the supernatant were determined with a time-resolved immunofluorometric assay (TRFIA). HBV DNA in supernatant and miR-122 in cells were measured by quantitative real-time PCR.

RESULTSAfter 48 h expressions of miR-122 in the LNA-antimiR-122 and anti-miR-122 groups were significantly suppressed and lower than those in the negative control (P<0.001), while the level of miR-122 in the hsa-miR-122 group was higher than that in the negative control (P<0.001). The expression of HBeAg and HBsAg in hsa-miR-122 group was lower than that in the negative control (P<0.01) 24 h and 48 h after transfection. The expression of HBeAg and HBsAg in the anti-miR-122 group and LNA-antimiR-122 group was significantly lower than that in negative control (P>0.001). The levels of viral DNA at both time-points in the various test groups were not significantly different from those of negative control group (P>0.05).

CONCLUSIONmiR-122 may regulate HBV antigens and potentially affect the progress of pathogenesis, which might be the new targets for treatment of HBV infection.

DNA, Viral ; genetics ; Hep G2 Cells ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B e Antigens ; metabolism ; Hepatitis B virus ; genetics ; Humans ; MicroRNAs ; genetics ; metabolism ; Transfection

OBJECTIVETo explore the effect of hepatitis B virus (HBV) X protein (HBX) on expression of the host gene Wnt induced secreted protein-1 (WISP-1) that is related to the pathogenic process of hepatocellular carcinoma (HCC).

METHODSTumor and paratumor tissues were collected from HCC patients, and normal liver tissues were collected from healthy controls. Immunohistochemistry was used to evaluate the in vivo presence and expression levels of HBX and WISP-1 in the three tissue types. HepG2 cells stably transfected with pc-DNA3.1(+)-HBX or with pc-DNA3.1(+) only (G0, control) were generated and used to examine in vitro the HBX-induced changes in WISP-1 expression at the mRNA and protein levels by reverse transcription polymerase chain reaction and western blotting, respectively.

RESULTSThe HCC tissues showed significantly higher rates of positivity for WISP-1 expression than the non-tumor controls (76.6% vs. paratumor: 23.4% or normal tissues: 0%, x2= 35.967, P less than 0.01). HBX increased WISP-1 expression in HepG2 cells at both the mRNA (1170.33 +/- 41.26 vs. G0: 265.34 +/- 27.47, t = 31.63, P less than 0.01) and protein (240.33 +/- 11.37 vs. G0: 40.33 +/- 7.09, F = 600.57, P less than 0.01) levels.

CONCLUSIONHBV may up-regulate expression of the host gene WISP-1 through its X protein and thus promote the development of HCC.

Carcinoma, Hepatocellular ; Hepatitis B ; Hepatitis B virus ; metabolism ; Humans ; Liver Neoplasms ; Wnt1 Protein

OBJECTIVETo investigate the intrahepatic expression of inducible nitric oxide synthase (iNOS) in patients with chronic hepatitis B (CHB) and its relation to liver histopathology.

METHODSThe intensity and distribution of the immunohistochemical staining of intrahepatic iNOS were studied in the liver biopsy specimens obtained from 74 patients with CHB and statistical analyses were performed between intrahepatic iNOS and ALT, HbeAg, HBV DNA grading of liver inflammation and staging of fibrosis. Seven histologically normal liver sections were used as a control group.

RESULTSCompared with the control group, the intrahepatic iNOS immunoexpression was significantly higher in patients with CHB (P < 0.05), iNOS immunoreactivity was observed mainly in hepatocytes showing a predominant cytoplasmic staining, with the positive liver cells distributed diffusely throughout the hepatic lobule. Immunopositive staining could also be detected in Kupffer cells, sinusoidal lining cells and vascular endothelial cells. Compared with patients with normal ALT, the hepatocellular iNOS immunoexpression was significantly higher in patients with elevated ALT (P < 0.05) and the iNOS immunoexpression was significantly correlated with the serum level of ALT (r=0.601, P=0.000). Statistical analysis also showed that the intrahepatic iNOS immunoexpression was positively correlated with the grading of liver inflammation and the staging of liver fibrosis (r=0.660, P=0.000; r=0.507, P=0.000). No significant correlation between iNOS and HBeAg and HBV DNA was detected. CONCLUSION The intrahepatic expression of iNOS is elevated in chronic hepatitis B patients and correlated well with the severity of the disease, which indicated that inducible nitric oxide synthase may have a critical role in the pathogenesis of chronic viral hepatitis B.

Adult ; Alanine Transaminase ; metabolism ; DNA, Viral ; metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Hepatitis B Antigens ; metabolism ; Hepatitis B virus ; metabolism ; Hepatitis B, Chronic ; enzymology ; metabolism ; pathology ; virology ; Hepatocytes ; metabolism ; Humans ; Male ; Nitric Oxide Synthase Type II ; metabolism

Occult HBV infection is characterized by the absence of serum HBsAg with persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms for the origin of occult HBV infection include strong suppression of viral replication and gene expression, mutation in the regulatory regions of HBV genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage of HBsAg secretion from infected hepatocytes. Standardized assays are not yet available, and sensitive HBV DNA amplification assay is necessary for the diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti-HBc positive population. However, neither anti-HBc nor anti-HBs can be detected in a significant proportion of infected persons. Occult HBV infection occurs in a number of clinical settings and is highly prevalent in HCV-infected patients as well as in patients with cryptogenic chronic liver disease including hepatocellular carcinoma.
DNA, Viral/analysis ; Hepatitis B/*diagnosis/*epidemiology/metabolism ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Humans

OBJECTIVETo screen and identify the protein interacting with HBV antigen in hepatocytes. Then investigate the biological functions of hepatitis B virus antigen in the pathogenesis of hepatitis B and seek effective methods to prevent and treat it.

METHODSThe yeast two-hybrid system-3 technique was used to construct HBV PreS2, HBeAg, HBcAg, HBxAg bait plasmids. The bait plasmids transformed the yeast AH109 and expressed themselves in it. After being identified by SDS-PAGE and Western blot, the AH109 yeast was mated with yeast Y187 containing liver cDNA library plasmid in 2 x YPDA medium to form diploid yeast and was then plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) and synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing x-alpha-gal for screening. Plasmids of blue colonies were extracted and transformed into Escherichia coli, then analyzed by DNA sequencing and bioinformatics. To further prove the interaction between HBV antigen and metallothionein, translation was performed by using reticulocyte lysate and coimmunoprecipitation was displayed in vitro.

RESULTSGenes coding for HBV antigen binding protein were successfully cloned and metallothionein was found in that protein. The interaction between HBeAg, HBcAg and HBxAg and metallothionein were further proved by coimmunoprecipitation in vitro.

CONCLUSIONThe interaction between HBV antigen and metallothionein indicates that metallothionein may participate in the pathogenesis of hepatitis B

Hepatitis B ; metabolism ; Hepatitis B Antigens ; chemistry ; Hepatocytes ; metabolism ; Humans ; Metallothionein ; chemistry ; Protein Interaction Mapping ; Two-Hybrid System Techniques