Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
J Gastroenterol. 2013 Oct;48(10):1188-204. doi: 10.1007/s00535-012-0737-2. Epub 2013 Feb 9.
Treatment for chronic hepatitis B has improved drastically with the use of nucleot(s)ide analogues (NAs). However, NA therapy typically fails to eliminate Hepatitis B virus (HBV) completely, and it is difficult to discontinue these therapies. We previously demonstrated that NA therapy induced immature viral particles, including HBV RNA in sera of chronic hepatitis B patients. In the study reported here, we analyzed the association between HBV RNA titer and the recurrence rate of hepatitis after discontinuation of NA therapy.
The study cohort comprised 36 patients who had discontinued NA therapy. Serum HBV DNA or DNA plus RNA levels were measured by real time PCR and statistical analyses were performed using clinical data and HBV markers.
At 24 weeks after discontinuation of NA therapy, HBV DNA rebound was observed in 19 of the 36 patients (52.8 %), and alanine aminotransferase (ALT) rebound was observed in 12 of 36 patients (33.3 %). Multivariate statistical analysis was used to identify factors predictive of HBV DNA rebound. The HBV DNA + RNA titer following 3 months of treatment was significantly associated with HBV DNA rebound [P = 0.043, odds ratio (OR) 9.474, 95 % confidence interval (CI) 1.069-83.957)]. Absence of hepatitis B e antigen (HBeAg) at the end of treatment was significantly associated with ALT rebound (P = 0.003, OR 13.500, 95 % CI 2.473-73.705). In HBeAg-positive patients, the HBV DNA + RNA titer after 3 months of treatment was marginally associated with ALT rebound (P = 0.050, OR 8.032, 95 % CI 0.997-64.683).
Monitoring of serum HBV DNA + RNA levels may be a useful method for predicting re-activation of chronic hepatitis B after discontinuation of NA therapy.
核苷（酸）类似物（NAs）的使用极大地改善了慢性乙型肝炎的治疗效果。然而，NA 治疗通常无法完全清除乙型肝炎病毒（HBV），并且难以停止这些治疗。我们之前的研究表明，NA 治疗诱导了不成熟的病毒颗粒，包括慢性乙型肝炎患者血清中的 HBV RNA。在本报告的研究中，我们分析了 HBV RNA 滴度与 NA 治疗停药后肝炎复发率之间的关系。
该研究队列包括 36 名已停止 NA 治疗的患者。通过实时 PCR 测量血清 HBV DNA 或 DNA 加 RNA 水平，并使用临床数据和 HBV 标志物进行统计分析。
在停止 NA 治疗后 24 周，36 例患者中有 19 例（52.8%）观察到 HBV DNA 反弹，36 例患者中有 12 例（33.3%）观察到丙氨酸氨基转移酶（ALT）反弹。多变量统计分析用于确定预测 HBV DNA 反弹的因素。治疗 3 个月后 HBV DNA + RNA 滴度与 HBV DNA 反弹显著相关[P=0.043，优势比（OR）9.474，95%置信区间（CI）1.069-83.957)]。治疗结束时 HBeAg 缺失与 ALT 反弹显著相关（P=0.003，OR 13.500，95%CI 2.473-73.705）。在 HBeAg 阳性患者中，治疗 3 个月后 HBV DNA + RNA 滴度与 ALT 反弹有一定相关性（P=0.050，OR 8.032，95%CI 0.997-64.683）。
监测血清 HBV DNA + RNA 水平可能是预测 NA 治疗停药后慢性乙型肝炎再激活的一种有用方法。
