The Role of Gene Quantitation of Pre-S Deletion and Basal Core Promoter/Precore Mutants and Protein Quantitation of Pre-S2 Mutant Protein in Predicting Hepatocellular Carcinoma in CHB Patients Receiving Entecavir Treatment.

Entecavir is capable of inhibiting hepatitis B virus (HBV) replication and has a low drug resistance rate. Entecavir therapy can improve liver inflammation and fibrosis and can also reduce the risk of HCC development in chronic hepatitis (CHB) patients. However, many treated patients develop HCC despite antiviral therapy. Thus, to investigate risk factors is crucial for clinicians to predict prognosis and aid decisions regarding HCC surveillance. However, due to genetic diversity and socioeconomic differences, the risk factors for HCC for Taiwanese CHB patients may not be the same as in other geographic areas. Thus it is crucial to validate whether these HCC risk factors can be applied to HCC in Taiwanese patients treated with entecavir. Because of the percentages of wild type and the HBV mutant are different in each chronic hepatitis B patients and these different HBV population may affect the prognosis of patients receiving antiviral therapy. Pyrosequencing has been applied to quantitate basal core promoter mutant and precore mutant. Gene chip has been used to quantitate pre-S mutant. ELISA has also been developed by Dr. Huang W (A Co-Investigator) to quantitate pre-S mutant LHBS (Large HBsAg). We aim to determine the predictors of HCC in CHB patients receiving entecavir, emphasize on HBV viral factors such as HBsAg quantitation, HBV viral load, HBV genotypes, especially on quantitation of basal core promoter and precore mutants and quantitation of pre-Si/2 deletion mutants. We expect that these factors can predict HCC in CHB patients receiving entecavir. Specific plan: 1. To determine the predictors of HCC development in CHB patients receiving long-term entecavir treatment. 2. To study the role of percentages of basal core promoter and precore mutants (by pyrosequencing) in predicting HCC in CHB patients receiving entecavir treatment. 3. To study the role of pre-S1/2 deletion mutants (by gene chip) and pre-S2 mutant LHBS (by ELISA) in predicting HCC in patients receiving entecavir treatment. Patient and Methods: A total of 1400 naive chronic hepatitis B infected-patients (including 550 patients from Kaohsiung Chang Gung Memorial Hospital; 350 patients from China Medical University Hospital and 500 patients from Keelung Chang Gung Memorial Hospital) who received at least 1 -year entecavir treatment will be analyzed. Host factor such as age, sex, ALT levels and HBeAg status at baseline will be recorded. HBV viral factors such as baseline HBV viral load, HBV genotypes will be determined. HBV DNA will be determined at baseline and every 3-6 months. HBsAg quantitation will be determined at baseline and every 6-12 months during treatment. Quantitation of basal core promoter and precore mutants and quantitation of pre-S1/2 deletion mutants and pre-S2 mutant LHBS at baseline will be performed. Nested case-controlled study will be performed to compare these factors between those with and without HCC development (matched with propensity score).

Project ID:PC10501-2374
External Project ID:MOST104-2314-B182-061-MY2