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

姚雅萍; 李波; 夏利芳; 郭楠; 代玉; 赵鹏; 张昕; 李夏; 黄磊; 李伯安

doi:10.12435/j.issn.2095-5227.2024.123

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: 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仍可检出。学术界将这部分病人分为低病毒血症(Low-level viremia，LLV)患者与极低病毒血症(Very low-level viremia，VLLV)患者¹。对于LLV，国内外均有所报道，而对于VLLV，目前讨论较少。
目的明确VLLV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，为临床工作中VLLV的防治提供证据支持。
方法选取解放军总医院第五医学中心2020年10月至2021年3月门诊和住院常规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及影像学检查的差异，同时对VLLV的影响因素进行Logistic回归分析。另外，在VLLV组中，将其分为HBV DNA≥20 IU/mL组和HBV DNA＜20 IU/mL组，分析两组临床资料的差异。
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、性别方面差异均无统计学意义(P＞0.05)。VLLV组的HBsAg定量M(IQR)：2 781.000(2 540.000 ~ 4 785.000) vs 604.000(67.510 ~ 870.000)，P＜0.001、AFPM(IQR)：2.680(1.740 ~ 3.800) vs 2.300(1.660 ~ 3.320)，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等关联(P＜0.05)。其中，HBsAg定量(OR=7.684，95% CI：3.289 ~ 17.950)与VLLV独立关联。亚组分析显示，病毒载量与疾病阶段、用药情况、用药时长、HBsAg定量、AST、ALT等不存在显著关系(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 in patients with hepatitis B virus infection who were negative by routine PCR, and to analyze the clinical characteristics and associated factors of VLLV, so as to provide evidence support 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 the PLA General Hospital from October 2020 to March 2021. The serum 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 difference of clinical data between the two groups was analyzed.
Results VLLV status was detected in 10.02% (100/998) of HBV infected patients. There was no significant difference in age and sex between VLLV group and HBV DNA negative group (P>0.05). The quantitative HBsAg (MIQR: 2 781.0002 540.000-4 785.000 vs 604.00067.510-870.000, P＜0.001), AFP(2.6801.740-3.800 vs 2.3001.660-3.320, 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 such patients should be strengthened in clinical practice.

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