Clinical Significance of the Hepatitis B Virus Genotype

B型肝炎病毒基因型之臨床意義

陳彬芳(Bing-Fang Chen)

《輔仁醫學期刊》 2卷4期 (2004/12) Pp. 273-282

摘要

B型肝炎病毒(HBV)依據病毒基因序列的差異度，大於8%者列為不同的基因型，因此目前至少共有8種不同之基因型，分別命名為基因型A至H。此8種HBV基因型分佈於不同的地理位置，並且可影響病毒致病的過程和治療之預後情形。例如在印度，感染HBV基因型D型的病人，和感染基因型A的病人相比，較常伴隨著嚴重的肝病，並且在年輕的患者易導致肝癌生成。相同地，在台灣，感染基因型C型的患者常伴隨著較嚴重的肝病，並且在非肝硬化之年輕肝癌患者體內則以感染基因型B型居多。但是在日本和中國，基因型B型的患者預後良好，並且發生肝癌機率很低。至於抗病毒治療的成效，就干擾素的療效而言，感染基因型D和C型的患者和感染基因型A和B型的患者相比，對干擾素之療效較差。然而針對lamivudine的療效，不同基因型的影響力說不大。目前科學家發現許多HBV病毒的突變株，突變的位置主要集中在某些區域，尤其是在basal core promoter (BCP)，precore (PC)和pre-S等區域。研究顯示在基因型A和C型病毒株，易出現BCP變異株，而PC突變株的產生則侷限於基因型B，C，和D型。類似地，基因型B和C型相比，pre-S缺損之突變株較常出現在感染基因型C之B型肝炎病毒的患者身上。此外，近來某些學者發現由不同基因型重組而產生之重組基因型，而重組的位置各不相同，至於這些重組基因型的臨床意義則有待未來的研究。總而言之，在致病性、療效、和病毒的特性上，不同HBV基因型之間確實有所差異，因此確認慢性B型肝炎患者身體內之HBV病毒基因型，應可提供更進一步的資訊以供臨床醫師進行臨床的診斷。然而造成這些差異的分子病毒因子，則有待學者進一步地探討。

關鍵字

B型肝炎病毒 ； 基因型 ； 肝癌 ； 重組

並列摘要

At least 8 genotypes of the hepatitis B virus (HBV) have been distinguished based on a divergence over the entire genomic sequence of ＞8%, and these are designated A to H. The 8 genotypes of HBV show a distinct geographical distribution and influence the course of the disease and the prognosis of treatment. Genotype D is associated with more severe liver disease than genotype A in India and may predict the occurrence of hepatocellular carcinoma (HCC) in young patients. Similarly, in Taiwan, genotype C is associated with more severe liver disease, while genotype B is associated with the development of HCC in young non cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. As to the response to antiviral treatment, genotypes D and C are associated with a lower response rate to interferon therapy compared with genotypes A and B. However, the influence of HBV genotypes on the outcome of lamivudine therapy remains less clear. Some HBV mutants have been found, and mutations are not distributed evenly over the entire genome but rather tend to cluster in particular parts of the viral DNA; in particular, the basal core promoter (BCP), the precore (PC) region, and the region of the pre-S gene. BCP variants tend to be more prevalent among genotypes A and C, while PC mutants seem to be restricted to genotypes B, C, and D. Likewise, pre S deletion mutants have been detected more frequently in carriers of HBV genotype C than in those of HBV genotype B. In addition, some recombinants between different genotypes have been found, whereas the exact hot spots of recombination and the clinical meaning of these recombinants need to be explored in the future. In summary, pathogenic, therapeutic, and virological differences do exist among these 8 known HBV genotypes, and determining the genotype in patients with chronic HBV infection will provide further information for clinical investigations. Further studies to clarify the molecular virological factors that contribute to these differences are required.

並列關鍵字

HBV ； genotype ； HCC ； recombination