The present study confirmed that older age and advanced fibrosis were important risk factors for HCC, and that HCC was the major cause of mortality in NASH patients with advanced fibrosis. Regular screening for HCC is thus extremely important for NASH patients with advanced fibrosis.

Hepatitis B virus (HBV) has a unique fourth openreading frame coding for a 16.5-kDa protein known as hepatitis B virus X protein (HBX). The importance of HBX in the life cycle of HBV has been well established, but the underlying molecular function of HBX remains controversial. We previously identified a proteasome subunit PSMA7 that interacts specifically with HBX in the Saccharomyces cerevisiae two-hybrid system. Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HBX and PSMA7. Analysis of the interacting domains among PSMA7, PSMC1, and HBX by deletion and site-directed mutagenesis suggested a mutually competitive structural relationship among these polypeptides. The competitive nature of these interactions is further demonstrated using a modified yeast two-hybrid dissociator system. The crucial HBX sequences involved in interaction with PSMA7 and PSMC1 are important for its function as a transcriptional coactivator. HBX, while functioning as a coactivator of AP-1 and acidic activator VP-16 in mammalian cells, had no effect on the transactivation function of their functional orthologs GCN4 and Gal4 in yeast. Overexpression of PSMC1 seemed to suppress the expression of various reporters in mammalian cells; this effect, however, was overcome by coexpression of HBX. In addition, HBX expression inhibited the cellular turnover of c-Jun and ubiquitin-Arg-␤-galactosidase, two well known substrates of the ubiquitin-proteasome pathway. Thus, interaction of HBX with the proteasome complex in metazoan cells may underlie the functional basis of proteasome as a cellular target of HBX.Human hepatitis B virus (HBV) 1 belongs to a group of hepadnaviruses that includes the hepatitis viruses of the woodchuck, ground squirrel, tree squirrel, Pekin duck, and heron. HBV has a unique fourth open reading frame, termed the hepatitis B virus X (HBX) gene. HBX gene is well conserved among the mammalian hepadnaviruses and codes for a 16.5-kDa protein (1, 2). The protein can activate the transcription of a variety of viral and cellular genes (3-5) and induce liver cancer in certain transgenic mouse model (6). Since HBX does not bind to DNA directly, its activity is thought to be mediated via protein-protein interactions. HBX has been shown to enhance transcription through AP-1 and AP-2 (7-9) and to activate various signal transduction pathways (10, 11). Several recent studies have also identified possible cellular targets of HBX, including members of the CREB/ATF family (12, 13), the TATA-binding protein (14), RNA polymerase subunit RPB5 (15, 16), the UV-damaged DNA-binding protein (17), and the replicative senescence p55 sen (18). HBX has also been shown to interact with p53 and inhibit its function (19,20). Furthermore, HBX possesses amino acid sequence homology to the functionally essential domains of Kunitz-type serine proteases inhibitors and mutation of this putative motif inactivates the transactivation function of HBX (21).Using the Saccharomyces cerevisiae two-hybrid syste...

It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core-related antigens are also significant factors independently associated with relapse of hepatitis.

Objective The present study was performed to clarify the ability of ultrasonography (US) and computed tomography (CT)