Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, 212003, PR China.
Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, 212003, PR China.
Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):310-316. doi: 10.1016/j.clinre.2018.10.017. Epub 2018 Dec 5.
We aimed to assess the long-term outcomes of e antigen-negative chronic hepatitis B (CHB) infection with low hepatitis B virus (HBV) DNA level (< 200 IU/mL) and persistently normal alanine aminotransferase (PNALT) and to explore the factors associated with the results.
This retrospective cohort study enrolled consecutive baseline CHB patients with PNALT from January 2005 to June 2008. In total, 252 e antigen-negative CHB patients with PNALT and low HBV DNA level (< 200 IU/mL) were enrolled, of whom 188 were eligible for this analysis. Among the 188 patients, 131 were followed up more than twice per year and 57 were followed up at least once per year, with a median follow-up period of 102 (73-123) months.
Of 188 patients, 16 had HBV DNA level of > 200 IU/mL and PNALT, 164 had HBV DNA level of < 200 IU/mL and PNALT and 8 had HBV DNA level of > 200 IU/mL and elevated ALT level, of which 3 used an antiviral drug during follow-up. Twelve of 164 experienced HBsAg loss. Cox regression analysis suggested that baseline HBsAg levels were associated with HBsAg loss in patients after follow-up, especially the baseline HBsAg levels of < 200 IU⁄mL, which is a risk factor for HBsAg loss. The AUC of baseline HbsAg level in the e antigen-negative CHB group was 0.772 (cutoff value 426, P < 0.001). The cumulative probability of HBsAg loss in the HBsAg < 400 IU/L group was 20% (7/35), which ws higher than that in the HBsAg ≥ 400 IU/L group (3.88%; 5/129; X2 = 11.75, P = 0.0006).
The e antigen-negative CHB infection with low HBV DNA level (< 200 IU/mL) and PNALT will progress to chronic hepatitis, although the probability of its occurrence is low. Spontaneous HBsAg loss may not occur frequently because the manifested cumulative probability of HBsAg loss was higher in the HBsAg < 400 IU/L group than in the HBsAg ≥ 400 IU/L group.
本研究旨在评估乙型肝炎病毒（HBV）DNA 水平低（<200IU/ml）且丙氨酸氨基转移酶（ALT）持续正常（PNALT）的 e 抗原阴性慢性乙型肝炎（CHB）患者的长期结局，并探讨与结果相关的因素。
本回顾性队列研究纳入了 2005 年 1 月至 2008 年 6 月期间基线时为 PNALT 的连续 CHB 患者。共纳入 252 例 e 抗原阴性 CHB 患者，PNALT 且 HBV DNA 水平低（<200IU/ml），其中 188 例符合分析标准。188 例患者中，131 例每年随访两次以上，57 例每年随访一次，中位随访时间为 102（73-123）个月。
188 例患者中，16 例 HBV DNA 水平>200IU/ml 且 ALT 升高，164 例 HBV DNA 水平<200IU/ml 且 ALT 正常，8 例 HBV DNA 水平>200IU/ml 且 ALT 升高，其中 3 例在随访期间使用抗病毒药物。164 例患者中，12 例发生 HBsAg 丢失。Cox 回归分析表明，随访后 HBsAg 丢失与患者的基线 HBsAg 水平有关，特别是基线 HBsAg 水平<200IU/ml，是 HBsAg 丢失的危险因素。HBsAg 水平<200IU/ml 的 e 抗原阴性 CHB 患者的 HBsAg 丢失的 AUC 为 0.772（临界值 426，P<0.001）。HBsAg<400IU/L 组的 HBsAg 丢失累积概率为 20%（7/35），高于 HBsAg≥400IU/L 组（3.88%；5/129；X2=11.75，P=0.0006）。
HBV DNA 水平低（<200IU/ml）且 ALT 正常的 e 抗原阴性 CHB 感染可能会进展为慢性肝炎，尽管其发生的概率较低。由于 HBsAg 丢失的累积概率在 HBsAg<400IU/L 组中高于 HBsAg≥400IU/L 组，因此自发性 HBsAg 丢失可能不会经常发生。
