[Interleukin-21 expression in serum of patients with acute-on-chronic liver failure and its significance].

OBJECTIVE: To investigate the level of the serum IL-21 and its correlation with serum biochemical indices of liver function test in patients with acute-on-chronic liver failure. METHODS: Sixty patients with acute-on-chronic liver failure (severe hepatitis group) and 18 normal cases (control group) were enrolled in the study. Peripheral blood lymphocytes were isolated and total RNA of lymphocytes was extracted by using Trizol. Real-time PCR was used to assay IL-21 mRNA level. The serum IL-21 expression level was detected by ELISA method. The correlation between IL-21 and ALT, AST, TBiL, ALB was analyzed using Pearson's correlation analysis, respectively. RESULTS: Serum IL-21 expression level in severe hepatitis group was higher than that of control group. Moreover, the difference between them was statistically significant (P < 0.05). Serum IL-21 level was positively correlated with serum ALT, AST, TBil, respectively (P < 0.05), but was negatively correlated with ALB, respectively (P < 0.05). CONCLUSION: Serum IL-21 expression level was increased in patients with acute-on-chronic liver failure and was associated with the severe of inflammation. We, therefore, believe that IL-21 might be involved in the pathogenesis of acute-on-chronic liver failure and might be an index of the severity of liver inflammation.

[Comparative study on the clinical characteristics of HBV/HCV co-infection patients with different HCV contaminnation mode].

OBJECTIVE: The purpose of this study was to compare the epidemiological, biochemical and virological characteristics among patients co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the mode of HCV contamination. METHODS: The study included 133 patients with chronic HBV/HCV co-infection. They were studied and subdivided into two groups (drug addicts group and Blood transfusion group) according to the mode of HCV contaminnation. The epidemiological, biochemical and virological characteristics were collected. Univariate analysis was performed with the SPSS 16.0. RESULTS: 78 patients were infected by the mode of drug addicts (IDU), whereas 55 were infected by the mode of blood transfusion( PTCH). Patients in drug addicts group had yonger age, shorter HBV and HCV infection history, and lower cirrhosis percentage than those of patients in PTCH group (P <0.05). However,serum levels of ALT (t =4.760, P =0.000), AST (t = 3.798, P = 0.000), TBil (t = 4.274, P = 0.000) of IDU patients were higher than those of PTCH patients. There was difference of sex composition between two groups (chi2 = 18.706, P = 0.000). CONCLUSIONS: The clinical characteristics of patients with HBV/HCV coinfection were significantly different among different HCV contamination mode. PTCH patients have the characteristics of older age, more cirrhosis and mild degree of liver injury; IDU patients have the characteristics of yonger age,fewer cirrhosis and severe liver injury.

[Adenoviruses mediated BCL-X1 overexpression protects mice from fulminant hepatic failure].

OBJECTIVE: To indentify the relation between hepatic cells apoptosis and the lesion of liver tissue in acute toxic lethal hepatitis. METHODS: 60 Wistar mice were randomly divided into normal control, model group and treatment group. Normal control and model group were pretreated by portal vein injection of normal saline, the treatment group was pretreated by portal vein injection of BCL-X1 adenoviruses. The mice of model group and treatment group were received an injection of D-galn and LPS to establish fulminant hepatic failure models 7 days after pretrement. To observe BCL-X1 expression, serum ALT, AST, hepatocyte apoptosis rate, and mortality rate of the three groups. RESULTS: The BCL-X1 expression was higher in treatment group than in model group; 6 hours after fulminant hepatic failure models were established,the serum ALT, AST level of treatment group was lower than model group;The hepatocyte apoptosis rate of treatment group was lower than model group. The death rate of treatment group was lower than model group. CONCLUSION: In fulminant mice hepatic failure models, the hepatocyte apoptosis rate has a positive correlation with death rate, the overexpression of BCL-X1 can decrease the hepatocyte apoptosis rate and the death rate.

[The levels of HBsAg can predict the efficacy of peglated interferon-alpha 2a combined with adefovir dipivoxil, in HBeAg-positive chronic hepatitis B patients].

OBJECTIVE: To investigate the levels of HBsAg in predicting the efficacy of peglated interferon-alpha 2a combined with adefovir dipivoxil (ADV), in HBeAg-positive chronic hepatitis B patients. METHODS: This trial enrolled 62 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, serum HBV DNA levels of at least 100 000 IU/ml. The efficacy assessment: viral suppression below 100 IU/ml. The patients with HBV DNA < or = 100 IU/ml after 24 weeks therapy were divided into group A, in which monotherapy continued; While the rest were divided into group B, in which ADV was combined until week 48. In group B, at the end-of-treatment, the patients with HBV DNA < or = 100 IU/ml were divided into group B1, the rest were divided into group B2. RESULTS: There was no significant difference on the baseline characteristics of patients between B1 and B2. There was significant difference on the levels of HBsAg at 12-week and 24-week between B1 and B2; while there was no significant difference on the levels of HBeAg. CONCLUSIONS: The levels of HBsAg at 12-week and 24-week would be predictors to evaluate the efficacy of combined therapy in HBeAg-positive chronic hepatitis B patients.

[A clinical study on the efficacy of HBeAg-positive chronic hepatitis B patients treated with adefovir dipivoxil for 4 years].

OBJECTIVE: To observe the efficacy and safety on the efficacy of HBeAg-positive chronic Hepatitis B patients treated with adefovir dipivoxil for 4 years. METHODS: Ninety-five patients with HBeAg-positive chronic hepatitis B were treated with adefovir dipivoxil 10 mg per day orally. The patients were observed before and after treatment for their serum levels of ALT and HBV DNA, the new increasing rates of serum ALT normalization, HBV DNA clearances, HBeAg loss, HBeAg seroconversion and adverse drug events. RESULTS: At 4 years on study, the rates of ALT normalization, HBV DNA clearances, HBeAg loss, HBeAg seroconversion and HBV DNA rebound were 89.5%, 63.2%, 47.4%, 41.1% and 8.0%, respectively. No drug related to renal function impairment was found during the treatment, eight patients had adverse drug events but all were mild. CONCLUSION: Adefovir dipivoxil could effectively inhibit HBV replication, normalize ALT and enhance transformation from HBeAg to HBeAb for cases with naive and treated-first patients. The efficacy were increased with prolongation of the treatment period. It is safe and has a good tolerance.

[Short-term efficacy of adefovir dipivoxil as an add-on therapy in the pegylated IFNalpha-2a treatment for HBeAg positive chronic hepatitis B patients].

OBJECTIVE: To investigate whether the combination therapy of pegylated IFNalpha-2a plus adefovir dipivoxil (ADV) improve the efficacy of the treatment in CHB patients with HBeAg positive or not. METHODS: 57 CHB patients with HBeAg positive received 48-week pegylated IFNalpha-2a therapy were enrolled into this study. If serum HBV DNA levels exceeded 1000 copies/ml at week 24, the patients were assigned to group A (pegylated IFN-alpha2a plus ADV, 21 cases) or group B (pegylated IFNalpha-2a only, 14 cases); otherwise, they received the unceasing monotherapy of pegylated IFNalpha-2a (group C, 22 cases). RESULTS: At week 48, HBeAg seroconversion rates were 23.8%, 28.6% and 63.6% (A vs C,P = 0.014), but rates of aminotransferases normalization and HBV DNA suppression (< 1000 copies/ml) were not statistically significant among three groups. But during week 24 to week 48, rates of HBeAg seroconversion, aminotransferases normalization and HBV DNA suppression were also not statistically significant between group A and B. But amplitude of DNA drop in group A was much more than that in group B (2.60 +/- 1.37 vs 0.86 +/- 2.09, P = 0.005). CONCLUSION: An ADV add-on therapy in pegylated IFNalpha-2a treatment seems able to improve the inhibition of HBV DNA in chronic hepatitis B patients with HBeAg positive. It requires a large, double-blind, randomized clinical trial to further provent.

[The effect of antiviral therapy for patients with HBeAg-negative cirrhosis].

OBJECTIVE: To investigate the efficacy of nucleot(s)ide analogues therapy in patients with HBeAg-negative cirrhosis in China. METHODS: 111 patiens with HBeAg-negative cirrhosis were divided into antiviral group (58 cases, 25 entecavir, 19 adefovir dipivoxil, 13 lamivudine, 1 telbivudine) and control group (53 cases, supportive and symptomatic treatment). These two groups were matched for demography, liver function and Child-Pugh score. RESULTS: At the 96th week, the rate of ALT normalization and HBV DNA drop (1g copies/ml) in antiviral group were higher than those in control group (P < 0.05). The rates of HBV DNA negative (< 500 copies/ml) were 88.7% (47/53) and 32. 5% (13/40), respectively (P < 0.05 ). There were no differences in the rates of developing HCC and undergoing variceal bleeding between antiviral group and control group (P > 0.5). 15.4% patients with lamivudine treatment emerged YMDD mutations. 10.5% patients with adefovir dipivoxil treatment emerged virologic breakthrough and hepatitis flare during the second year. 2 patients (3.5%) in treatment group and 6 patients (11.5%) in control group died of liver failure or variceal bleeding or HCC ( P > 0.05 ). CONCLUSIONS: Neucleot(s)ide analogues are effective in suppressing HBV replication in patients with HBeAg-negative cirrhosis, but the impact of which on the mortality and complications of cirrhosis should be prolongly observed. For continuing treatment, the neucleot(s)ide analogues with strong effective and low resistance are the first choices to prevent viral mutation and drug resistance.