Lu Jiahui, Zhang Congnan, He Pengyuan, Ou Mengdang, Xia Jinyu, Huang Mingxing
Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Liver Res. 2022 Feb 18;6(1):39-44. doi: 10.1016/j.livres.2022.02.001. eCollection 2022 Mar.
Several effective antiviral drugs are now available; however, the risk of liver-related complications is still present. Low-level viremia (LLV), defined as a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load lower than 2000 IU/mL, is one of the major factors responsible for these complications. It has been reported that 22.7-43.1% of patients with HBV experience LLV. Herein, we aimed to explore the risk factors for very LLV (VLLV) during antiviral treatment.
We collected data of patients with chronic hepatitis B (CHB) who received nucleos(t)ide analog treatment from October 2016 to April 2021. VLLV was defined as an HBV DNA load of 9-20 IU/mL. A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.
Seropositivity rates for hepatitis B e antigen (HBeAg) (45.3% . 17.3%, < 0.001) and hepatitis B surface antigen (HBsAg, 3.11 ± 0.68 lg IU/mL . 2.54 ± 1.04 lg IU/mL, < 0.001) and alanine aminotransferase levels (30.34 ± 15.08 U/L . 26.15 ± 16.66 U/L, = 0.040) in the two groups were significantly different. The multivariate analysis showed that both HBeAg seropositivity (adjusted odd ratio (aOR), 3.63; 95% confidence interval (CI): 1.98-6.64; < 0.001) and HBsAg levels (aOR, 2.21; 95% CI: 1.53-3.20; < 0.001) are independent risk factors for VLLV. During the multivariate analysis in the subgroup of HBeAg-positive patients, male gender (aOR, 3.68; 95% CI: 1.23-10.76; = 0.017) and high HBsAg (aOR, 4.86; 95% CI: 1.73-13.64; = 0.003) levels were significantly correlated with VLLV. However, this was not the case in HBeAg-negative patients ( > 0.050). HBeAg seropositivity (aOR, 5.08; 95% CI: 2.15-12.02; < 0.001 . aOR, 2.78; 95% CI: 1.16-7.00; = 0.022) and HBsAg levels (aOR, 2.75; 95% CI: 1.41-5.37; = 0.003 . aOR, 2.10; 95% CI: 1.27-3.46; = 0.004) significantly increased the risk of VLLV, irrespective of the age group. Both HBsAg (area under the receiver operating characteristic curve (AUC), 0.681; 95% CI: 0.623-0.736; < 0.001) and HBeAg (AUC, 0.640; 95% CI: 0.581-0.697; < 0.001) had certain predictive value for VLLV.
HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence. When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks, emphasis should be placed on the potential occurrence of VLLV, warranting the use of highly sensitive HBV DNA detection methods.
目前已有多种有效的抗病毒药物；然而，肝脏相关并发症的风险依然存在。低水平病毒血症（LLV）定义为乙肝病毒（HBV）脱氧核糖核酸（DNA）载量低于2000 IU/mL，是导致这些并发症的主要因素之一。据报道，22.7% - 43.1%的乙肝患者会出现LLV。在此，我们旨在探讨抗病毒治疗期间极低水平病毒血症（VLLV）的危险因素。
我们收集了2016年10月至2021年4月接受核苷（酸）类似物治疗的慢性乙型肝炎（CHB）患者的数据。VLLV定义为HBV DNA载量为9 - 20 IU/mL。根据年龄和性别，将139例LLV患者与139例获得持续病毒学应答的患者按1:1比例进行匹配。
两组患者的乙肝e抗原（HBeAg）血清学阳性率（45.3% 对17.3%，< 0.001）、乙肝表面抗原（HBsAg，3.11 ± 0.68 lg IU/mL对2.54 ± 1.04 lg IU/mL，< 0.001）以及丙氨酸氨基转移酶水平（30.34 ± 15.08 U/L对26.15 ± 16.66 U/L，= 0.040）存在显著差异。多因素分析显示，HBeAg血清学阳性（校正比值比（aOR），3.63；95%置信区间（CI）：1.98 - 6.64；< 0.001）和HBsAg水平（aOR，2.21；95% CI：1.53 - 3.20；< 0.001）均为VLLV的独立危险因素。在HBeAg阳性患者亚组的多因素分析中，男性（aOR，3.68；95% CI：1.23 - 10.76；= 0.017）和高HBsAg水平（aOR，4.86；95% CI：1.73 - 13.64；= 0.003）与VLLV显著相关。然而，在HBeAg阴性患者中情况并非如此（> 0.050）。无论年龄组如何，HBeAg血清学阳性（aOR，5.08；95% CI：2.15 - 12.02；< 0.001对aOR，2.78；95% CI：1.16 - 7.00；= 0.022）和HBsAg水平（aOR，2.75；95% CI：1.41 - 5.37；= 0.003对aOR，2.10；95% CI：1.27 - 3.46；= 0.004）均显著增加VLLV的风险。HBsAg（受试者工作特征曲线下面积（AUC），0.681；95% CI：0.623 - 0.736；< 0.001）和HBeAg（AUC，0.640；95% CI：0.581 - 0.697；< 0.001）对VLLV均有一定的预测价值。
HBeAg血清学阳性和较高的HBsAg水平不仅是VLLV的危险因素，还可预测其发生。对于CHB患者，抗病毒治疗48周后若仍HBeAg血清学阳性且HBsAg水平高，应重视VLLV的潜在发生，有必要采用高灵敏度的HBV DNA检测方法。
