Viral Polymerase Genetic Variation and Acute Exacerbation in Chronic Hepatitis B: Longitudinal Study

• Main Authors: Pei-Yun Cheng, 鄭佩芸
• Other Authors: Ming-Whei Yu
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/70013906293693893816

碩士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 100 === Background and Aims: Acute exacerbation (AE) occurs frequently in hepatitis B surface antigen (HBsAg) carriers, especially in those positive for HBeAg. During the course of persistent hepatitis B virus (HBV) infection, AE is likely related to the break of balance between virus and host immune response, and HBV genetic variation may trigger AE. The aim of this study was to clarify the association between HBV sequence variations and AE, and to investigate change in Pol gene sequence before, during, and after exacerbation. Materials and Methods: We prospectively studied 52 patients with exacerbation of hepatitis B Pol gene sequence using plasma sample collected at baseline, before alanine aminotransferase (ALT) peak, ALT peak, and after ALT peak, respectively. Fifty-two subjects who h ad persistently normal serum ALT during follow-up served as controls. A total of 160 HBV DNA samples were amplified by nested polymerase chain reaction (PCR) from sera and were directly sequenced. We then analyze the relationship between HBV evolutionary pattern and specific nucleotide/amino acid variants and acute exacerbation. Results: AE cases had a significantly higher level of serum ALT and HBV DNA than controls at baseline. Baseline genetic distance was statistically lower in cases than in controls at the nucleotide level (9.68*10-3 vs. 11.7*10-3, p=0.031), but no such association was found at ALT peak (12.1*10-3 vs. 13.8*10-3, p=0.329). Among AE cases, the genetic distance was also higher at ALT peak when compare with other time points at marginal statistical significance (12.1*10-3 vs. 10.2 *10-3, p=0.071). After point-by-point screening the nucleotide/amino acid positions in the whole Pol gene region, we have revealed the association between AE and variant types at nucleotide and amino acid positions, nt1080 (OR 0.32, p 0.0288), nt1126 (OR 0.33, p 0.0453), nt1242 (OR 0.34, p 0.0346), nt2619 (OR 0.32, p 0.0433), nt2444 (OR 4.07, p 0.0157), aa17 (OR 0.28, p 0.048), aa46 (OR 4.28, p 0.0116) . Conclusion: Our data suggest no clear evidence for the association between rate of viral divergence and the occurrence of AE. Certain single nucleotide polymorphism may serve as predictive of AE.