Wu I-Chin, Chow Nan-Haw, Cheng Pin-Nan, Liu Wen-Chun, Young Kung-Chia, Chang Wei-Lun, Chen Chi-Yi, Tseng Kuo-Chih, Chang Ting-Tsung
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
J Med Virol. 2007 Jun;79(6):663-9. doi: 10.1002/jmv.20822.
A study was conducted during a 1 year follow-up to characterize the viral kinetics in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and to develop a model of predicting the probability of spontaneous HBeAg seroconversion. Fifty-seven patients with HBeAg-positive chronic hepatitis B were enrolled with monthly follow-ups from three Phase III clinical trial placebo groups. According to serial viral loads, 30 patients (52.6%) with the stationary pattern maintained stable HBV DNA levels with fluctuations of less than 1.5 log copies/ml. Twenty patients (35.1%) with the declining pattern exhibited a spontaneous decline of more than 1.5 log copies/ml without a following rebound of at least 1.5 log copies/ml. The remaining seven patients (12.3%) had the wavering pattern. Both declining and wavering patterns, when compared with the stationary pattern, had significantly higher hepatic necroinflammation in terms of ALT and Knodell scores at the baseline and peak ALT levels during the follow-up period. The declining pattern had a significantly better clinical outcome in terms of the lowest final HBV DNA and a reduction in the necroinflammatory score after 1 year. Furthermore, the declining pattern had a favorable HBeAg seroconversion rate (40%) compared with the wavering (14.3%) and stationary patterns (0%). A regression equation, incorporating simultaneous serum bilirubin, ALT, and HBV DNA levels, predicted the probability of HBeAg seroconversion with a sensitivity of 76.8% and a specificity of 74.7%. In conclusion, different viral kinetic patterns in patients with chronic hepatitis B implicate distinct clinical significance and immunologic perspective.
一项为期1年的随访研究旨在描述乙肝e抗原（HBeAg）阳性慢性乙型肝炎的病毒动力学特征，并建立一个预测HBeAg自发血清学转换概率的模型。57例HBeAg阳性慢性乙型肝炎患者来自三项III期临床试验安慰剂组，每月进行随访。根据连续的病毒载量，30例（52.6%）呈稳定模式的患者维持稳定的HBV DNA水平，波动小于1.5 log拷贝/ml。20例（35.1%）呈下降模式的患者表现出自发下降超过1.5 log拷贝/ml，且随后至少1.5 log拷贝/ml没有反弹。其余7例（12.3%）呈波动模式。与稳定模式相比，下降模式和波动模式在基线时的ALT和Knodell评分以及随访期间的ALT峰值水平方面，肝坏死炎症明显更高。就最终最低HBV DNA和1年后坏死炎症评分的降低而言，下降模式的临床结果明显更好。此外，下降模式的HBeAg血清学转换率（40%）优于波动模式（14.3%）和稳定模式（0%）。一个纳入同时期血清胆红素、ALT和HBV DNA水平的回归方程预测HBeAg血清学转换概率的灵敏度为76.8%，特异度为74.7%。总之，慢性乙型肝炎患者不同的病毒动力学模式具有不同的临床意义和免疫学观点。
