Lai Wei

Hepatic steatosis in chronic hepatitis B patients is associated with metabolic factors more than viral factors

Background and Aims:u2002 Hepatic steatosis is commonly seen in chronic hepatitis C (CHC) patients. It has been reported to be associated with both metabolic factors and viral factors, and affects the severity of fibrosis in CHC. However, the relationship between hepatic steatosis and chronic hepatitis B (CHB) is unclear. The aims of this study were to investigate the frequency of hepatic steatosis in CHB patients, to identify the factors associated with its presence, and assess the relationship between the stage of steatosis and the severity of fibrosis.

Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa-2b in HBeAg-positive patients.

Background and Aim:u2002 To evaluate the usefulness of quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for predicting HBeAg seroconversion in chronic hepatitis B patients treated with conventional interferon (IFN) alfa‐2b or PegIFN alfa‐2b.

Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma

To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphisms (SNPs) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, three SNPs in the IL28B gene (rs12979860C/T, rs8099917G/T and rs12980275G/A) were examined in 330 subjects (including 154 HBV-related HCC patients, 86 non-HCC patients with chronic hepatitis B (CHB), 43 HBV self-limited infections and 47 healthy controls). Notably, the frequency of CC homozygosity was 91.5% in healthy controls and 72.9% in CHB, the difference being statistically significant (χ2xa0=xa06.40, Pxa0=xa00.01). The statistically difference was seen between healthy controls (91.5%) and HCC (74.7%) (χ2xa0=xa06.05, Pxa0=xa00.01). However, this significant finding was not seen between HBV self-limited and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (χ2xa0=xa04.44, Pxa0=xa00.04). Haplotype analyses revealed significant association between haplotype C–T–A and healthy controls, but not with the HCC group (96.6 vs. 82.0%, χ2xa0=xa06.08, Pxa0=xa00.01). Analyses of genotype combination and gene–gene interaction showed that there was a positive interaction between rs12979860 and rs12980275, with an OR rate of 11.79 (likelihood test, Pxa0=xa00.04). Our results suggest that the IL28B rs12979860 C/T polymorphism might affect susceptibility to the chronic HBV infection and progression of HCC. Of note, the T allele and non-CC genotypes have strong predictive effect of increasing susceptibility of chronic HBV infection and HCC.

Transplanted endothelial progenitor cells ameliorate carbon tetrachloride–induced liver cirrhosis in rats

Cirrhosis is the most common end stage of liver diseases, and there are no effective treatment methods. Here we evaluated the effect of endothelial progenitor cell (EPC) transplantation from rat bone marrow (BM) on the development of cirrhosis induced by carbon tetrachloride (CCl4). Ex vivo generated, characterized, and cultivated rat BM–derived EPCs were identified by their vasculogenic properties in vitro. EPCs from male rats were transplanted into female rats via the intraportal vein 12 weeks after they had been challenged with CCl4, and the rats were killed 16 weeks later. The control rats received only a saline infusion. The fibrosis index and donor cell engraftment were assessed after EPC transplantation. After transplantation via the portal vein, PKH26 labeling, polymerase chain reaction, and in situ hybridization analysis revealed that the donor EPCs had adhered to the vasolateral surfaces of blood vessels and established in the liver. EPCs reduced the expression of α‐smooth muscle actin, collagen III, and transforming growth factor β (P < 0.05) as well as levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the serum (P < 0.05), but at the same time they increased the levels of albumin and Ki67. CCl4 treatment increased the international prothrombin ratio (P < 0.05) and reduced albumin levels, whereas EPCs restored these parameters to normal levels. These results suggest that EPC transplantation could play a role in regulating hepatocyte regeneration and ameliorating established liver cirrhosis. Liver Transpl 15:1092–1100, 2009.

Senescence marker protein 30 in acute liver failure: validation of a mass spectrometry proteomics assay

BackgroundOur previous proteomic study showed that the senescence marker protein (SMP30) is selectively present in the plasma of a murine model of acute liver failure (ALF). The aim of this study was to validate this SMP30 expression in the plasma and liver tissues of mice and humans with ALF.MethodsAfter the proteomic analysis of plasma from a murine model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced ALF by two-dimensional electrophoresis (2-DE) and mass spectrometry, the expression levels of SMP30 in the plasma and liver tissues were validated by western blot and RT-PCR analyses. These results were then confirmed in plasma samples from humans.ResultsThese data validate the results of 2-DE, and western blot showed that SMP30 protein levels were only elevated in the plasma of ALF mice. Further analysis revealed that GalN/LPS induced the downregulation of SMP30 protein levels in liver tissues (by approximately 25% and 16% in the GalN/LPS-treated mice and in the treated mice that survived, respectively; P < 0.01). Hepatic SMP30 mRNA levels decreased by about 90% only in the mice that survived the GalN/LPS treatment. Importantly, plasma obtained from patients with ALF also contained higher levels of SMP30, about (3.65 ± 0.34) times those observed in healthy volunteers.ConclusionThis study shows that SMP30 is not only a potential biomarker for the diagnosis and even prognosis of ALF. It also plays a very important role in a self-protective mechanism in survival and participates in the pathophysiological processes of ALF.

Proteome responses to stable hepatitis B virus transfection and following interferon alpha treatment in human liver cell line HepG2

Hepatitis B virus (HBV) infection is a worldwide health problem and may develop to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. To investigate the global proteome responses of liver‐derived cells to HBV infection and IFNα treatment, 2‐DE and MS‐based analysis were performed to compare the proteome changes between HBV stably transfected cell line HepG2.2.15 and its parental cell line HepG2, as well as HepG2.2.15 before and after IFNα treatment (5000u2005IU/mL for 72u2005h). Compared to HepG2, 12 of 18 down‐regulated and 27 of 32 up‐regulated proteins were identified in HepG2.2.15. After IFNα treatment, 6 of 7 down‐regulated and 11 of 14 up‐regulated proteins were identified. Differentially expressed proteins caused by HBV infection were involved with cytoskeletal matrix, heat shock stress, kinases/signal transduction, protease/proteasome components, etc. Prohibitin showed a dose‐dependent up‐regulation during IFNα treatment and might play a potent role in anti‐HBV activities of IFNα by enhancing the crossbinding p53 expression to achieve the apoptosis of HBV infected liver cells. Down‐regulation of interferon‐stimulated gene 15 (ISG15) in HepG2.2.15 and recovery by IFNα suggested its relationship with IFNαs anti‐HBV effect.

Polymorphisms of interferon-inducible genes OAS associated with interferon-α treatment response in chronic HBV infection.

To evaluate the role of host single nucleotide polymorphisms (SNPs) of 2,5-oligoadenylate synthetase (OAS) in predicting IFN response in patients with HBV infection, OAS gene and four SNPs were examined in 363 patients with chronic HBV infection (including 41 patients with HBsAg seroconversion) and 57 healthy controls. One SNP and three haplotypes were identified after adjustment for age, sex, HBV DNA. The frequency of OAS3T/C heterozygotes is 52.2% in responders (R) and 38.2% in non-responders (NR), with an odds ratio (OR) of 1.511 (P = 0.018). For complete responders (CR) and NR, the OR reached 2.323(P = 0.023). Haplotype analyses revealed significant association between three OAS haplotypes and response to IFN-α treatment. Genotype combination and interaction between gene-gene analyses disclosed that there was a positive interaction between OAS2/OAS3 and OAS3/OASL, and the rate of OR was 2.46 (likelihood test, P = 0.004) and 4.46 (likelihood test, P = 0.004), respectively. Our results suggest that OAS gene variations may play an important role in response to IFN-α and provide a novel strategy for the resolution of HBV infection.

Characterization of microRNA expression profiles associated with hepatitis B virus replication and clearance in vivo and in vitro

Background and Aim:u2002 Alpha interferon (IFN‐α) is an approved treatment for chronic hepatitis B (CHB). MicroRNA (miRNA) are currently known as a part of IFN‐mediated antiviral defense. We aimed at characterizing the miRNA expression associated with hepatitis B virus (HBV) replication and IFN‐mediated HBV clearance.

Role of ISGF3 in modulating the anti-hepatitis B virus activity of interferon-alpha in vitro

Background and Aim:u2002 Although interferon‐α (IFN‐α) is an effective treatment for hepatitis B virus (HBV) infection, its precise mechanism of action has not been identified. In this study, we investigated the role of signal transduction pathways in the activation of anti‐HBV responses mediated by IFN‐α.

Performance evaluation and comparison of the newly developed Elecsys anti-HCV II assay with other widely used assays.

BACKGROUNDnAnti-HCV assays remain the first choice for screening HCV infection in most clinical laboratories. The Elecsys anti-HCV II assay has been recently launched and we aimed to evaluate its performance compared with other widely used methods.nnnMETHODSnFour seroconversion panels, 861 consecutive sera under routine clinical conditions, 100 preselected sera with low positive anti-HCV results and 178 samples from patients infected with HIV were tested using Elecsys anti-HCV II, Architect anti-HCV and Vitros anti-HCV assays. Confirmatory testing was performed using RIBA and HCV RNA tests. Moreover, 203 samples with different HCV genotypes were assessed using Elecsys anti-HCV II.nnnRESULTSnElecsys anti-HCV II detected seroconversion 7-14 days earlier than the Architect and Vitros assays. Furthermore, it had 100% sensitivity and superior specificity in screening routine clinical samples, including those with low positive anti-HCV, and detected 97.6% (122/125) anti-HCV-positive samples from HIV-infected patients with HCV viremia. However, the anti-HCV levels in the genotype 3b samples were slightly underestimated.nnnCONCLUSIONSnElecsys anti-HCV II shortens the seroconversion window. It is suitable for screening HCV infection in clinical samples, including those from immunocompromised patients, due to the excellent sensitivity and specificity. Further investigation of the subtype inclusivity in a larger sample number might be warranted.