Hypomethylation of TNF-alpha gene promoter in the patients with acute-on-chronic hepatitis B liver failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>The present study was designed to investigate the possible epigenetic alteration in the promoter of TNF-alpha in the patients with acute-on-chronic hepatitis B liver failure (ACHBLF).</p><p><b>METHODS</b>The methylation of TNF-alpha promoter in peripheral blood mononuclear cells (PBMCs) was measured by methylation specific PCR (MSP). The level of serum TNF-alpha was determined by enzyme-linked immunosorbent assay (ELISA). Model for End-stage Liver Disease (MELD) was performed for the evaluation of liver failure.</p><p><b>RESULTS</b>The serum level of TNF-alpha in patients with ACHBLF(44.9260 +/- 26.48523) was higher than that in CHB (18.92505 +/- 9.04461) and healthy controls (11.9172 +/- 5.04612) (P < 0.05). Moreover, the serum TNF-alpha level was significantly decreased in methylation group as compared to unmethylaiton group in patients with ACHBLF (P < 0.05). MELD was not significantly different between methylated and unmethylated group of ACHBLF patients (P > 0.05). In addition, the serum level of TNF-alpha was found to be positively correlated with serum total bilirubin (r = 0.891, P < 0.01) and MELD score (r = 0.792, P < 0.01), but to be negatively correlated with prothrombin activity (r = - 0.511, P < 0.05) in patients with ACHBLF.</p><p><b>CONCLUSION</b>The TNF-alpha methylation patten is stable for the liver failure, suggesting the effect of environment on methylation.</p>

Study of oxidative stress in chronic hepatitis B patients with elevated serum total bilirubin / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate oxidative stress in chronic hepatitis B (CHB) patients with elevated serum total bilirubin (TBIL).</p><p><b>METHODS</b>75 CHB patients with elevated serum TBIL were enrolled in the present study. A, B, C, D and E group were defined. Serum Malondialdehyde (MDA), Xanthine Oxidase (XOD), Vitamin C (V(C)) and Vitamin E (V(E)) were determined. The control group contained 11 healthy donors and the carrier group contained 16 Hepatitis B surface antigen (HBsAg) carriers.</p><p><b>RESULTS</b>The concentrations of MDA and XOD were significantly higher in each group of patients than in the control (P < 0.05), while V(C) and V(E) were significantly lower (P < 0.05). The concentration of XOD was significantly higher in the carrier group than in the control (P < 0.05), while MDA, V(C) and V(E) were not significantly different (P > 0.05). The concentrations of MDA and XOD were significantly positively correlated with TBIL (r = 0.670, P < 0.01; r = 0.737, P < 0.01, respectively) in the patients, while V(C) and V(E) were significantly negatively correlated with TBIL (r = -0.463, P < 0.01; r = -0.247, P < 0.05, respectively). The concentration of MDA was significantly different among all the groups in the patients except the comparison between group A and group B. The concentration of XOD was significantly different between group A, B, C and group D, E (P < 0.05). The concentration of V(C) was significantly different between group A and group D, E and between group B, C, D and group E (P < 0.05). The concentration of V(E) was significantly different between group A, B and group E (P < 0.05).</p><p><b>CONCLUSION</b>There was a disturbance between oxidative stress and anti-oxidative ability in CHB patients with elevated serum TBIL. Oxidative stress became more serious along with the increasing of serum TBIL. In HBsAg carriers, oxidative stress level was low. The results suggest antioxidant treatment for CHB patients with elevated serum TBIL may help to improve the effect of therapy.</p>

Increased expression of inducible nitric oxide synthase in chronic hepatitis B patients is correlated with histopathological grading and staging / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the intrahepatic expression of inducible nitric oxide synthase (iNOS) in patients with chronic hepatitis B (CHB) and its relation to liver histopathology.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Compared 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.</p>

Oxidative stress in patients with chronic hepatitis B before and after interferon alpha-2b treatment / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the impacts of interferon alpha-2b (IFN alpha-2b) on the oxidative stress states in the treatment of chronic hepatitis B (CHB) with different genotypes.</p><p><b>METHODS</b>Thirty-five patients with chronic hepatitis B and 18 healthy volunteers as a control were enrolled in this present study. In control and patients group, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum malondialdehyde (MDA) levels, serum total antioxidative stress capacity (TAC) were measured spectrophotometrically. After the therapy with interferon alpha-2b at the dose of 300 million units via intramuscular injection thrice a week for 12 weeks, these parameters were measured again in the patient group. The genotypes of hepatitis B virus were detected by polymerase chain reaction and hybridization. The effective group was defined as the patients with complete response and partial response.</p><p><b>RESULTS</b>The elevated concentrations of MDA and impaired levels of TAC in the patients with CHB were observed as compared to the healthy controls (P < 0.05 for both). There were no significant differences in serum levels of MDA and TAC in CHB patients with various genotypes (P > 0.05). The serum levels of MDA after the treatment with IFN alpha-2b were significantly lower than the pretreatment levels (P < 0.05), which even returned to the normal concentration (P > 0.05) in the effective group. There were significant increases in the TAC after the IFN alpha-2b therapy in the effective group. However, the significant differences in the TAC levels before and after the INFalpha-2b treatment were not observed in the non-responsive group.</p><p><b>CONCLUSION</b>The oxidative stress could be improved with IFN alpha-2b treatment of chronic hepatitis B patients. The results suggest that antioxidant treatment for chronic hepatitis B patients may help improve the effect of anti-virus therapy.</p>

Nitric oxide and nitric oxide synthase in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate nitric oxide (NO) and nitric oxide synthase (NOS) in patients with chronic hepatitis B.</p><p><b>METHODS</b>Nitric oxide and nitric oxide synthase, including inducible NOS (iNOS) and constitutive NOS (cNOS), were measured in patients and control groups, then were statistically analyzed.</p><p><b>RESULTS</b>NO and iNOS were significantly higher in patients with hepatitis B than in the controls (P < 0.05). NO and iNOS were significantly higher in patients with increased ALT than in the controls and in patients with normal ALT (P < 0.05). NO was significantly higher in patients with normal ALT than in the controls (P < 0.05). cNOS were not significant different among these groups. NO and iNOS significantly correlated with ALT in patients with hepatitis B (r=0.367 and r=0.474). No significant relationship was found among NO, NOS and HBV DNA. Among different genotype groups, NO and NOS had no significant difference.</p><p><b>CONCLUSION</b>NO and NOS were higher in patents with chronic hepatitis B. In patients with increased ALT, NO's damage was severe. In patients with normal ALT, there was no significant damage caused by NO. NO should be detected in patients with hepatitis B in addition to HBV markers.</p>

Hemorheologic changes in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the variation of the hemorheology in patients with chronic hepatitis B and study its relations with HBV DNA, liver function and oxidative stress markers.</p><p><b>METHODS</b>Indices for hemorheology, oxidative stress markers, liver function, and HBV DNA were measured in 55 patients with chronic hepatitis B and correlative analysis was made.</p><p><b>RESULTS</b>The low-shear whole blood viscosity (BV), RBC aggregation index were significantly higher in hepatitis B group than those in the control group (P < 0.05), Hematocrit (HCT), the low-shear BV, RBC aggregation index were significantly higher in the patients whose ALT was higher than the patients whose ALT was normal and the controls. No significant difference was found in HBV DNA and indices of hemorheology (P > 0.05), nor in indices of hemorheology and oxidative stress markers (P > 0.05).</p><p><b>CONCLUSION</b>There is disturbance of microcirculation and oxidative stress in the body of patients with chronic hepatitis B. The hemorheology and oxidative stress markers should be regarded as useful indexes in patients with chronic hepatitis B in addition to HBV markers.</p>