Quantitative hepatitis B surface antigen combined with hepatitis B e antigen as sustained virological response predictors during extended therapy with Peginterferon alfa-2a for hepatitis B e antigen-positive chronic hepatitis B.

BACKGROUND: The best strategy for chronic hepatitis B patients with poor response to 48 weeks of Peginterferon-based therapy has been controversial and the predictive value of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels for determining the sustained virological response (SVR) of these patients is uncertain. OBJECTIVES: To optimize management of these patients and evaluate the use of these serobiomarkers to predict SVR. STUDY DESIGN: Eighty-one patients with an unsatisfactory response after 48 weeks of Peginterferon-based therapy were treated with extended Peginterferon therapy with or without nucleo(s) tide analogues (NAs), for a total of 96 weeks of Peginterferon treatment. HBsAg, HBeAg and HBV DNA levels were measured serially during the treatment and follow-up. RESULTS AND CONCLUSIONS: Twenty-six of 81 patients (32.1%) attained SVR during the 72-week follow-up. The SVR rate was not statistically different between groups receiving 1-year prolongation of Peginterferon with or without NAs. The serum HBsAg cut-off of 1800IU/mL at week 48 had area under curve (AUC) of 0.727, and the serum HBsAg cut-off of 1500IU/mL, combined with HBeAg loss at week 72, had AUC of 0.753 to predict SVR during the follow-up. In conclusion, extended treatment with Peginterferon with or without NAs for patients with unsatisfactory response after 48 weeks of Peginterferon-based therapy is a promising strategy to achieve SVR, and quantitative serum HBsAg at week 48 and HBsAg level combined with HBeAg loss at week 72 of therapy can predict SVR to prolongation therapy with Peginterferon.

[The associated research on the expression of RUNX3 mRNA and protein in hepatic cell carcinoma as well as the relationship with clinical pathological parameters].

OBJECTIVE: To investigate the expression of RUNX3 mRNA and protein in hepatic cell carcinoma (HCC) and surrounding normal tissue, to analyze the relationship between RUNX3 expression and clinical pathological parameters. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to detect the expression of RUNX3 mRNA and protein in HCC and surrounding normal tissue respectively, and their relationship with clinical pathological parameters were analyzed. RESULTS: The relative expression value of RUNX3 mRNA found in 51 cases HCC was 0.4509 +/- 0.0963, and that did in 51 cases surrounding normal tissue was 0.9147 +/- 0.0222. The difference of RUNX3 mRNA expression between two kinds of samples was statistically significant (t = 33.6087, P < 0.001). The positives rate of RUNX3 protein expression found in 51 cases HCC tissue was 49.02% (25/51) and that did in 51 cases surrounding normal tissue was 82.35% (42/51). The difference of RUNX3 protein expression between two kinds of samples was statistically significant (chi2 = 12.5706, P < 0.005). The difference of RUNX3 mRNA and protein expression in some clinical pathological parameters involving differentiation degree, invasion, cancer thrombus and diversion in liver were statistically significant (P < 0.05). However that were not in another clinical pathological parameters involving gender, cancer diameter, cancer location as well as hemorrhage and necrosis of cancer, histotype (P > 0.05). CONCLUSION: The expression of RUNX3 mRNA and protein in HCC were significantly lower than that in surrounding normal tissue. The lower expression of runx3 protein in the HCC probably plays an important role in the tumorigenesis and development of HCC. The RUNX3 gene may be an anti-oncogene of HCC.

Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis.

OBJECTIVE: To investigate predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B (CHB) patients and their diagnostic values in hepatic inflammation and fibrosis. METHODS: A total of 106 HBeAg-negative CHB patients with clinically and pathologically proven steatosis and 98 patients without steatosis were recruited into this study. The levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (CHOL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), globulin (Glb), HBV DNA, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR) and pathological changes of the liver in inflammation, fibrosis and fatty deposition were examined in all patients. RESULTS: The levels of BMI, HOMA-IR, FBG, insulin, TG, and CHOL were significantly higher in patients with steatosis than those without steatosis (all P<0.05). But ALT, AST and HBV DNA levels were significantly lower in patients with steatosis (all P<0.05). Logistic regression analysis showed that only FINS was a significant predictor for hepatic steatosis (P<0.05); FINS and Glb were significant predictors for hepatic inflammation (all P<0.05); BMI and TC were significant predictors for hepatic fibrosis (all P<0.05). CONCLUSIONS: Hepatic steatosis, a common disease in HBeAg-negative CHB patients, was positively associated with BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. In these patients, the prevalence of hepatic inflammation and fibrosis was also increased.

[Effects of interferon on hepatic intercellular adhesion molecule-1 expression in patients with chronic hepatitis B].

OBJECTIVE: To investigate the effects of interferon -alpha1b (IFN-alpha1b) on hepatic intercellular adhesion molecule-1 (ICAM-1) expression and serum HBV DNA in patients with chronic hepatitis B. METHODS: Before and 6 months after IFN-alpha1b treatment, liver biopsy was performed in patients with chronic hepatitis B to detect the expression of ICAM-1 in the liver tissues using immunohistochemistry. Serum HBV load was detected with real-time fluorescence polymerase chain reaction. RESULT: CAM-1 expression in the liver tissue was significantly down-regulated after IFN treatment in patients with severe and moderate chronic hepatitis B (P<0.05). No significant variation was noted in the expression of ICAM-1 in the livers of patients with mild chronic hepatitis B after the treatment (P>0.05). In the patients weakly positive for ICAM-1 expression (+), serum HBV DNA varied scarcely after the treatment (P>0.05), while in the patients with strong ICAM-1 positivity (++, +++, or ++++), significant variation of serum HBV DNA occurred after the treatment (P<0.05 or P<0.01). CONCLUSION: The therapeutic effect of IFN-alpha1b is associated with the expression of ICAM-1 in the hepatocytes, and its expression might enhance the effects of IFN on HBV DNA in patients with chronic hepatitis B.

[A clinical and pathological study of nonalcoholic fatty liver disease].

OBJECTIVE: To study the pathological and clinical features of nonalcoholic fatty liver disease (NAFLD). METHODS: Grades and stages of liver lesions in 41 patients with NAFLD were analyzed. The relationships between pathohistological features of the livers, serum biochemical parameters, ultrasound examination and other clinical data of the patients were studied. RESULTS: Among the 41 patients with NAFLD (there were 21 with their liver fatty degeneration in grade 1, 15 in grade 2, and 5 in grade 3). There were 2 of grade 0, grade 1 had 25, grade 2 had 10, grade 3 had 3, and grade 4 had 1. Stage 0 of fibrosis was 20, stage 1 was 14, stage 2 was 4, stage 3 was 2, and stage 4 was 1. Degree of fatty degeneration was not positively associated with the body mass index (BMI) of the patients and the ultrasound findings in their livers. Grading of the inflammation was positively related to the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and ultrasound findings in their livers, but negatively to the platelet counts. Staging of fibrosis of the livers was positively related to the blood ALT, AST, GGT, and ALP, and negatively to triglyceride levels and platelet counts. CONCLUSIONS: Degree of liver fatty degeneration was not associated with grades of inflammation and staging of fibrosis of the liver. BMI, ALT and AST level, platelet counts, and ultrasound grades of fatty liver were associated with the liver histopathological changes of NAFLD patients. Liver biopsy is the essential way to make a diagnosis of NAFLD.

[Histological study of livers from the patients with chronic hepatitis B treated with bicyclol].

OBJECTIVE: To study histological changes of the livers in patients with chronic viral hepatitis B treated with bicyclol tablets. METHODS: Thirty one patients with chronic viral hepatitis B were divided into two groups and were treated with bicyclol orally at doses of 150 mg daily or 75 mg daily for 36 weeds. The histological changes of the livers were observed before and after the treatment. RESULTS: Compared with pre-treatment findings, there were significant differences in histological activity index in each group (P < 0.01, P < 0.05), there were also significant differences between the two groups (P < 0.05). Decreased inflammatory reaction was also seen (P < 0.05). CONCLUSION: Daily use of 150 mg and 75 mg bicyclol tablets are effective in improving liver histological changes in chronic hepatitis B patients. Bicyclol 150 mg daily was better.