Relationship Between Hepatitis B Virus Replication, Acute Exacerbation Of The Disease, And Liver Histopathology In Chronic Hepatitis B Patients

OBJECTIVE: Hepatitis B virus (HBV) is a major health problem worldwide and it is estimated that 350 million individuals are chronically ir.fected with this virus. Chronic HBV infection may be associated with a large spectrum of disease ranging from the status of healthy carrier of hepatitis B surface antigen (HBsAg) to a moderate or severe chronic hepatitis susceptible of evolution to cirrhosis and development of hepatocellular carcinoma(HCC) . Episodes of acute exacerbation (AE) are a common and important feature in the natural history of chronic hepatitis B (CHB). Liver injury in many patients with chronic hepatitis B is often characterized by acute exacerbation alternating with relatively normal liver function. These patients with chronic hepatitis B who have active liver disease almost invariably have serological evidence of active hepatitis B virus (HBV) replication. HBV genome (HBV DNA) is the most sensitive and direct marker of active HBV replication. Furthermore, HBV DNA quantification provides valuable information on the level of HBV replication and can be used as a prognostic indicator of liver disease or an index of response to antiviral drugs. The popular tests for assessing hepatitis activity are plasma alanineaminotransferase (ALT) and Aspartate aminotransferase (AST). liver biopsies is the best standard for evaluation of liver injury.The objectives of this study are (1)to quantitatively evaluate changes of serum level of HBV DNA in patients with chronic hepatitis B in multiple episodes of acute exacerbation. (2) to analyse the relationship between HBV DNA level in serum and the acute hepatic exacerbation of the disease in chronic hepatitis B patients.(3)to clarify the relationship between replication of hepatitis B virus and liver histopathology in the patients with chronic hepatitis B in acute exacerbation. These studies will help to better understand the mechanisms of repeatedly acute exacerbation of the patients in choronic hepatitis B.METHODS: 1. 83 patients with chronic hepatitis B were chosen in this study. The patients consisted of 8 women and 75 men, whose ages ranged from 17 to 48 years. They all had a HBsAg positive in serum for more than 1 year and multiple episodes of acute exacerbations of liver injury. We divided the patients ir.to four groups: CD Sera from 11 patients were collected before, during and after AE. (2) Sera from 16 hepatitis B "e" antigen (HBeAg)-positive patients and 9 antibody to HBeAg(ar.ti-HBe) -positive patients were collected during and after AE.(3) Sera from 2 patients with chronic hepatitis B and a patient with HBV-reduced cirrhosis were collected at time of multiple episodes of acute exacerbation during a 1-2 year follow-up . (3) Liver biopsies were obtained from 44 patients with chronic hepatitis B in episodes of acute exacerbation. Each specimen wasfixed in 10% formalin and embedded in paraffin. Histologic sections were cut successively and were stained with hematoxylin and eosin. According to their hepatic histopathlogical activities (GO-G4) , we divided the 44 patients into four groups:4 cases in G1 group, 13 cases in G2 group, 22 cases in G3 group,5 cases in G4 group. Then according to their stage of liver fibrosis (SO-S1), the 44 patients were placed in another four groups again, they were: 12 cases in SI group , 9 cases in S2 group , 19 cases in S3 group , 4 cases in S4 group . Serum samples were obtained from each patient on the day of the liver biopsy simultaneously. (5) 5 blood donors served as control group.The serum HBV DNA concentrations were tested by the quantitative polymerase chain reaction (PCR) using the AmpliSensor assay. In addition, routine plasma biochemical liver tests such as ALT AST and total bilirubin were assayed as well.RESULTS: (1) Quantitative PCR products showed that serum HBV DMA levels of 11 patients were 7 .14812 .008 (logarithm) within 2 ~ 8 weeks before ALT peak , increased to 8.416±2.160 (logarithm) at the time that ALT reached its peak, and decreased to 6.093±1.428 (logarithm) following the declin...