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慢性乙肝病毒感染患者极低病毒血症的临床特点及关联因素分析

Clinical characteristics and associated factors of very low-level viremia in patients with chronic HBV infection

    摘要
  • 摘要:
    背景 部分乙型肝炎病毒(hepatitis B virus，HBV)患者血清中的HBV DNA在常规PCR下检测不到，但使用高度敏感的实时PCR可检出，学术界将这部分患者分为低病毒血症(low-level viremia，LLV)患者与极低病毒血症(very low-level viremia，VLLV)患者。LLV在国内外均有报道，而VLLV目前讨论较少。
    目的 明确VLLV患者在常规PCR检测阴性的乙肝病毒感染患者中所占的比例，分析VLLV的临床特点及关联因素。
    方法 选取2020年10月—2021年3月于解放军总医院第五医学中心门诊和住院常规PCR检测HBV DNA阴性的(低于检测下限40 IU/mL)乙肝病毒感染患者，采用高敏HBV DNA技术检测患者血清中的病毒载量，根据检测结果分为VLLV组(5 ~ 40 IU/mL)和阴性组(＜5 IU/mL)，比较两组患者血常规、血生化、乙肝病毒标志物水平和影像学检查结果，同时对VLLV的关联因素进行Logistic回归分析。另外，将VLLV组分为HBV DNA≥20 IU/mL和HBV DNA＜20 IU/mL两个亚组，比较两亚组临床资料的差异。
    结果 共纳入998例常规检测阴性的乙肝病毒感染者，高敏HBV DNA检测阳性(即VLLV) 100例，阳性率10.02%。VLLV组与阴性组在年龄、性别方面的差异均无统计学意义(P＞0.05)。VLLV组的HBsAg定量M(IQR)：2 781.00(2 540.00 ~ 4 785.00) IU/mL vs 604.00(67.51 ~ 870.00) IU/mL，P＜0.001、甲胎蛋白M(IQR)：2.68(1.74 ~ 3.80) ng/mL vs 2.30(1.66 ~ 3.32) ng/mL，P=0.020、HBeAg阳性率(39.13% vs 23.22%，P=0.001)高于阴性组，差异均有统计学意义。VLLV组的慢性肝损害比例高于阴性组(70.00% vs 59.51%，P=0.042)。VLLV与疾病阶段、用药情况、HBsAg定量、AST、ALT等有关(P＜0.05)。其中，HBsAg定量(OR=7.684，95% CI：3.289 ~ 17.950)与VLLV独立关联。VLLV亚组分析显示，不同病毒载量组间的疾病阶段、用药情况、用药时长、HBsAg定量、AST、ALT等无统计学差异(P＞0.05)。
    结论 高HBsAg定量患者发生VLLV的概率较高，在临床工作中应对此类患者加强监测。

     

    Abstract:
    Background With the increased sensitivity of nucleic acid detection, HBV DNA in serum of some hepatitis B virus (HBV) patients is undetectable by conventional PCR, but can still be detected using highly sensitive real-time PCR. The academic community divided these patients into low-level viremia (LLV) patients and very low-level viremia (VLLV) patients. For LLV, both at home and abroad have been reported, while for VLLV, there are few international discussions.
    Objective To determine the proportion of VLLV patients with hepatitis B virus infection detected to be negative by routine PCR, and analyze the clinical characteristics and associated factors of VLLV, so as to provide evidence for the prevention of VLLV in clinical work.
    Methods A total of 998 patients with HBV infection whose HBV DNA was lower than 40 IU/mL were selected from the Fifth Medical Center of Chinese PLA General Hospital from October 2020 to March 2021. The sera viral load of the patients was detected by high sensitivity HBV DNA technology. According to the detection results, the patients were divided into VLLV group (5-40 IU/mL) and HBV DNA negative group (< 5 IU/mL). Blood routine, biochemical, HBV markers and imaging examination were compared between the two groups. The influencing factors of VLLV were analyzed by logistic regression. In addition, the VLLV group was divided into HBV DNA≥20 IU/mL group and HBV DNA < 20 IU/mL group, and the differences of clinical data between the two groups were analyzed.
    Results VLLV status was detected in 10.02% (100/998) of HBV infected patients. There was no significant difference in age and gender between VLLV group and HBV DNA negative group (P>0.05). The quantitative HBsAg (MIQR: 2 781.00 2 540.00-4 785.00 vs 604.00 67.51-870.00, P＜0.001), AFP (2.68 1.74-3.80 vs 2.30 1.66-3.32, P=0.020) and positive rate of HBeAg (39.13% vs 23.22%, P=0.001) of the VLLV group were significantly higher than those of the HBV DNA negative group. The proportion of chronic liver damage in the VLLV group was significantly higher than that in the HBV DNA negative group (70.00% vs 59.51%, P=0.042). VLLV was related to disease stage, drug use, quantification of HBsAg, AST, ALT, etc (P<0.05). Among them, quantification of HBsAg (OR=7.684, 95% CI: 3.289-17.950) was independently related to VLLV. Subgroup analysis showed that viral load was not significantly associated with disease stage, drug use, drug duration, HBsAg quantification, AST, ALT, etc. (P > 0.05).
    Conclusion Patients with high HBsAg quantification have a higher probability of VLLV, and monitoring of such patients should be strengthened in clinical practice.

     

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