Genomic change in hepatitis B virus associated with development of hepatocellular carcinoma

AIM: To determine the genomic changes in hepatitis B virus(HBV) and evaluate their role in the development of hepatocellular carcinoma(HCC) in patients chronically infected with genotype C HBV.METHODS: Two hundred and forty chronic hepatitis B(CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter(BCP), and precore regions of HBV were sequenced using the direct sequencing method.RESULTS: All of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25(10%) had C1653 T and 33(14%) had T1753 V mutation in X region; 157(65%) had A1762T/G1764 A mutations in BCP region, 50(21%) had G1896 A mutation in precore region and 67(28%) had pre-S deletions. HCC occurred in 6 patients(3%). The prevalence of T1753 V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753 V mutant, which were significantly higher than 1% and 1% in those with wild type HBV(P < 0.001).CONCLUSION: The presence of T1753 V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.

Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion.Although the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions.Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine.Japan is geographically close to Korea,and academic exchanges are active.Additionally,Korean doctors are familiar with Western style medical terminology.As a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea.To solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss of nuclear polarity,thick and irregular nuclear membrane,and nucleoli.