Clinical Significance of the Hepatitis B Virus Pre-S Deletion

B型肝炎病毒前表面抗原缺損之臨床意義

陳彬芳(Bing-Fang Chen)

《輔仁醫學期刊》 8卷2期 (2010/06) Pp. 85-95

摘要

慢性B型肝炎為一個全球且重要之健康課題。慢性B型肝炎感染的臨床預後可能為無症狀的帶原，慢性肝炎，肝硬化，和肝癌。由於B型肝炎病毒(HBV)之病毒反轉錄酶本身不具校正的功能，易發生錯誤，所以在宿主之免疫力的壓力下，病毒基因體會進行演化而產生變異株。這些變異株修改了免疫辨識之重要表位(epitope)以躲過免疫的巡囉。B型肝炎病毒之前表面基因缺損(pre-S deletion)變異株在慢性B肝感染的患者之臨床重要性越來越被重視。確實在之前的研究顯示，於帶有肝硬化和肝癌之慢性B型肝炎的帶原者血中，常見HBV前表面基因缺損(pre-S deletion)突變株的存在，因此推測出現前表面基因缺損(pre-S deletion)突變株可能會造成更嚴重的肝臟損壞，最後導致肝癌生成。至於慢性B肝的治療上，e抗原陰性的B肝患者若帶有前表面基因缺損，對干擾素治療的效果較好。在潛在性B肝病毒感染的患者中，亦可以發現前表面基因缺損(pre-S deletion)變異株的存在。此外，在前表面基因的位置上發現不同基因型重組的現象，至於確實的重組的位置和它的臨床意義則有待未來的研究。簡而言之，在慢性B型肝炎感染的致病性、療效、和病毒的特性上，前表面基因缺損突變株確實有其重要性，因此建議定期地偵測慢性B型肝炎患者是否出現前表面基因缺損突變株，以找出可能衍生肝臟疾病的高危險群，和適合投以干擾素治療的患者。同時，未來需要投注更多的心力，研究前表面基因缺損突變株在導致肝臟疾病和抗病毒療效之分子機轉。

關鍵字

B型肝炎病毒 ； 前表面基因缺損 ； 突變株 ； 肝癌 ； 潛在性B肝病毒

並列摘要

Chronic hepatitis B is an important global health problem. The clinical outcomes of chronic hepatitis B infection include an asymptomatic carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Because of the spontaneous error rate of viral reverse transcriptase, the hepatitis B virus (HBV) genome evolves during the course of infection under the antiviral pressure of the host immunity. These HBV variants display alterations of epitopes important for host immune recognition leading to escape from immune surveillance. The clinical significance of pre-S deletion mutants has become increasingly recognized in patients with chronic HBV infection. Previous studies showed that pre-S deletions were often identified in hepatitis B carriers with liver cirrhosis and HCC and suggested that the emerging pre-S deletion mutants may contribute to more-progressive liver damage and ultimately hepatocarcinogenesis. As to the treatment of chronic hepatitis B, hepatitis B e antigen (HBeAg)-negative patients with the presence of pre-S deletions were shown to have a good response to interferon therapy. Pre-S deletion variants were also found in occult HBV infection. In addition, some recombinants between different genotypes were found in the pre-S region, whereas the exact hot spots of recombination and the clinical meaning of these recombinants need to be further explored in the future. In summary, the pathogenic, therapeutic, and virological significance of pre-S deletions exists in patients with chronic HBV infection. It is recommended that pre-S deletion mutations be routinely determined in HBV carriers to help identify those who may be at a higher risk of liver disease progression and who are most appropriate for interferon treatment. In the future, additional investigations are needed to explore the molecular mechanisms of these pre-S deletion mutants and their involvement in the pathogenesis of each stage of liver disease and response to antiviral treatments.

並列關鍵字

hepatitis B virus HBV ； pre-S deletion ； mutant ； hepatocellular carcinoma HCC ； occult HBV