Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma

The aim of this study was to investigate whether there was a particular hep atitis B virus (HBV) X protein (HBx) mutant associated with Taiwanese patie nts with hepatocellular carcinoma (HCC). Initially, the entire coding regio n of HBx gene from the serum samples of 14 Taiwanese patients were sequence d. A novel mutant, HBx-A31, was preferentially found in patients with HCC. Sera from 67 patients with HCC and 100 patients with chronic hepatitis B we re thus subjected for codon 31 analysis using a dual amplification created restriction site method. HBx-A31 was detected more frequently in patients w ith HCC (52% versus 12%; P<0.001) and in patients with liver cirrhosis (44% versus 6%; P<0.001). Site directed mutagenesis experiment revealed that HB x-A31 was less effective in transactivating HBV enhancer I-X promoter compl ex, less efficient in supporting HBV replication, and less potent in enhanc ing TNF-alpha induced increment of CPP32/caspase 3 activities in HepG2 cell s. In conclusion, a prevalent HBx mutant was identified in Taiwanese patien ts with hepatocellular carcinoma. Development of this mutant might represen t a strategy of the virus to escape immune surveillance and thus contribute to the process of multiple-step hepatocarcinogenesis.