ABSTRACT: T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acute-on-chronic hepatitis B liver failure (ACHBLF) still remains obscure.
This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF.
This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction.
We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end-stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients.
These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients.
Digestive Diseases and Sciences 03/2012; 57(3):667-74. · 2.12 Impact Factor
ABSTRACT: Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ(2) = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.
The Tohoku Journal of Experimental Medicine 01/2012; 228(1):43-51. · 1.24 Impact Factor
ABSTRACT: To investigate oxidative stress in chronic hepatitis B (CHB) patients with elevated serum total bilirubin (TBIL).
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.
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).
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.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 04/2010; 24(2):131-3.