A 13-year longitudinal study of the impact of double mutations in the core promoter region of hepatitis B virus on HBeAg seroconversion and disease progression in patients with genotype C chronic active hepatitis
A 13-year longitudinal study of the impact of double mutations in the core promoter region of hepatitis B virus on HBeAg seroconversion and disease progression in patients with genotype C chronic active hepatitis
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DOI：
10.1111/j.1365-2893.2006.00788.x
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发表时间：
2007-03-01
影响因子：
2.5
通讯作者：
Yoon, S. K.
中科院分区：
文献类型：
--
作者：
Jang, J. W.;Lee, Y. C.;Yoon, S. K.
乙型肝炎病毒（HBV）核心启动子（CP）突变（T1762/A1764）在乙型肝炎e抗原（HBeAg）血清转化或疾病进展中的致病作用尚不清楚。我们在长达15年的长期随访期间调查了这些突变的临床相关性。在这项纵向队列研究中，29例hbeag阳性的活检证实慢性活动性肝炎无肝硬化患者定期监测bb10年。利用活检当天获得的冷冻肝组织对病毒分离物进行表征。在基线时比较有和没有HBV CP突变的患者的长期结果。HBV基因分型显示100%的研究对象感染了基因型C型HBV。在12.5年的中位随访期间，基线时没有HBV双CP突变的患者比双CP突变的患者（6.9年vs 9.4年，P = 0.062）有更早实现HBeAg血清转化的趋势。基线时的双CP突变也与肝硬化或肝细胞癌的最终发展显著相关（P = 0.013），而在最后一次随访时，双CP突变的缺失预示着无活性载体状态（P = 0.027）。在10年时，没有HBV双CP突变的患者的肝脏相关测试也明显优于有这些突变的患者，这反映在更高的血小板计数和白蛋白水平上（P = 0.036和P = 0.044）。双T1762/A1764突变与hbeag阳性基因型C型活动性肝炎患者肝脏恶化显著相关。在HBV CP区携带这些突变的患者中，较长时间的免疫清除加上延迟的HBeAg血清转化似乎有助于疾病进展。
The pathogenic role of core promoter (CP) mutations (T1762/A1764) of hepatitis B virus (HBV) in hepatitis B e antigen (HBeAg) seroconversion or disease progression remains unclear. We investigated the clinical relevance of these mutants over a long-term follow-up period of up to 15 years. In this longitudinal cohort study, 29 HBeAg-positive patients with biopsy-proved chronic active hepatitis without cirrhosis were regularly monitored for > 10 years. The viral isolates were characterized, using the frozen liver tissue obtained on the day of biopsy. Long-term outcomes were compared between patients with and without CP mutations of HBV at baseline. HBV genotyping showed that 100% of study subjects were infected with genotype C HBV. During a median follow-up period of 12.5 years, patients without double CP mutations of HBV at baseline showed a tendency towards achieving an earlier HBeAg seroconversion than those with (6.9 vs 9.4 years, P = 0.062) double CP mutations. Double CP mutations at baseline were also significantly associated with the eventual development of cirrhosis or hepatocellular carcinoma (P = 0.013), whereas the absence of double CP mutations predicted inactive carrier status at the last follow-up (P = 0.027). At 10 years, liver-related tests were also significantly better in patients without double CP mutations of HBV than in those with these mutations, as reflected by higher platelet counts and albumin levels (P = 0.036 and P = 0.044, respectively). Double T1762/A1764 mutations are significantly related to liver deterioration in HBeAg-positive genotype C active hepatitis patients. A longer period of immune clearance coupled with delayed HBeAg seroconversion appears to contribute to disease progression in patients harbouring these mutations in the CP region of HBV.