HBV管理中的无创检测：何时使用定量HBsAg和弹性成像

StephenW

Noninvasive Testing in HBV Management: When to Use Quantitative HBsAg and Elastography
         

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Anna Christina L. dela Cruz, MD
University of Kentucky
Lexington, Kentucky




Part of a case-based online initiative: What I Do and Why: HBV Treatment Strategies for Diverse Patient Populations



In general, an HBV DNA level < 2000 IU/mL, a negative hepatitis B e antigen (HBeAg), and a normal alanine aminotransferase (ALT) defines inactive chronic hepatitis B (CHB) infection. However, patients with immune-active HBeAg-negative CHB can have fluctuating liver enzymes and DNA levels that mimic the results seen in patients with inactive chronic hepatitis B infection. Therefore, distinguishing between inactive infection and immune-active HBeAg-negative CHB is essential in the decision to treat or monitor and in predicting the risk for hepatocellular carcinoma (HCC) and progression. Patients who are true inactive carriers do not require treatment, and quantitative hepatitis B surface antigen (qHBsAg) can be a valuable tool in identifying true inactive carrier status.



Quantitative HBsAg
qHBsAg can be a marker for the amount and activity of covalently closed circular DNA inside hepatocytes. In one study, an HBV DNA level < 2000 IU/mL and an HBsAg level < 1000 IU/mL identified inactive carriers with a diagnostic accuracy of 94.3%. These HBV DNA and qHBsAg cutoffs have also been associated with a lower risk for HCC and liver disease progression. In addition, patients with very low HBsAg (< 100 IU/mL) in combination with an HBV DNA < 2000 IU/mL have a high probability of spontaneous HBsAg clearance. The AASLD guidelines also note that HBeAg-negative patients in the “gray zone”—those who have HBV DNA or ALT levels that are borderline between inactive infection and immune-active HBeAg-negative CHB—may be differentiated with a 1-time qHBsAg test assessed in combination with their HBV DNA level.
qHBsAg levels have been explored in both HBeAg-negative and HBeAg-positive CHB for its roles in the natural course of HBV infection, in predicting response to pegIFN or nucleos(t)ide analogue therapy, and in coinfections with HCV, HDV, and HIV.
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Liver Biopsy and Elastography in Patients With CHB and Inactive Carriers
For patients in the “gray zone,” the AASLD guidelines recommend liver biopsy to determine the degree of fibrosis and inflammation. Although an inactive carrier will have absent/minimal necroinflammation on biopsy, AASLD guidelines note that these patients may have variable degrees of fibrosis both on liver biopsy and noninvasive fibrosis testing.



However, some patients are hesitant to have a biopsy, and there is the potential for sampling error. The preferred noninvasive fibrosis test is elastography. If HBV DNA is < 2000 IU/mL and ALT is elevated, other causes of liver enzyme elevation should be examined. Transient elastography (TE) has demonstrated very good diagnostic accuracy in patients with CHB (AUROC > 0.88 for stages F2-F4). Although more costly, magnetic resonance elastography (MRE) more accurately distinguished fibrosis stage in patients with CHB (AUROC > 0.96 for stages F1-F4). MRE may be valuable in patients with a BMI > 40, in whom TE has variable reliability. EASL guidelines recommend a liver biopsy for either patients who have a normal ALT and a liver stiffness measurement (LSM) of 6-9 kPa on TE or patients with an elevated ALT up to 5 times the upper limit of normal and an LSM of 6-12 kPa.



What I Do in My Practice
In my practice, I do not routinely order qHBsAg for all patients with CHB, but I have found qHBsAg to be very helpful in differentiating between inactive carrier status and immune-active HBeAg-negative CHB in certain scenarios. These include:

    Patients with normal ALT, an HBV DNA maintaining or fluctuating slightly > 2000 IU/mL (eg, 2200-5000 IU/mL), conflicting information such as a low LSM but slightly coarse liver on imaging, and hesitation to have a liver biopsy

    Patients who have borderline elevated ALT and/or HBV DNA and intermediate LSM on TE

    Patients who have other causes of elevated ALT such as nonalcoholic steatohepatitis with borderline or fluctuating HBV DNA

    Or any patient whose HBV DNA or ALT levels are borderline between inactive infection and immune-active HBeAg-negative CHB who are hesitant to have liver biopsy

If a patient in any of the above scenarios has an HBsAg > 1000 IU/mL, this suggests to me that the patient is likely not an inactive carrier but rather has immune-active HBeAg-negative CHB and may be at higher risk for HCC and liver disease progression. This will push my decision toward starting antiviral treatment and initiating HCC screening.



Your thoughts
Do you use qHBsAg in your clinical practice? In what situations have you obtained a qHBsAg?
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StephenW

HBV管理中的无创检测：何时使用定量HBsAg和弹性成像

安娜·克里斯蒂娜·德拉·克鲁兹（MD）
肯塔基大学
肯塔基州列克星敦

基于案例的在线计划的一部分：我做什么和为什么做：针对不同患者群体的HBV治疗策略



通常，HBV DNA水平<2000 IU / mL，乙型肝炎e抗原（HBeAg）阴性和丙氨酸氨基转移酶（ALT）正常定义为非活动性慢性乙型肝炎（CHB）感染。但是，具有免疫活性的HBeAg阴性CHB的患者可能具有波动的肝酶和DNA水平，可以模仿在非活动性慢性乙型肝炎患者中看到的结果。因此，在决定治疗或监测以及预测肝细胞癌（HCC）和进展的风险时，区分非活动性感染和免疫活性HBeAg阴性CHB是至关重要的。真正无效的携带者无需治疗，定量的乙型肝炎表面抗原（qHBsAg）可能是确定真正无效的携带者状态的宝贵工具。



定量乙肝表面抗原
qHBsAg可以作为肝细胞内共价闭合环状DNA数量和活性的标记。在一项研究中，HBV DNA水平<2000 IU / mL和HBsAg水平<1000 IU / mL可以鉴定出无活性的携带者，诊断准确性为94.3％。这些HBV DNA和qHBsAg临界值也与HCC和肝病进展的较低风险相关。此外，HBsAg极低（<100 IU / mL）与HBV DNA <2000 IU / mL相结合的患者极有可能自发清除HBsAg。 AASLD指南还指出，“灰色地带”的HBeAg阴性患者-HBV DNA或ALT水平处于非活动性感染与免疫活性HBeAg阴性CHB之间的界限-可以通过1次qHBsAg测试来区分结合其HBV DNA水平进行评估。
已在HBeAg阴性和HBeAg阳性CHB中研究了qHBsAg的水平，因为其在HBV感染的自然过程中，在预测对pegIFN或核苷类似物治疗的反应以及在HCV，HDV和HIV合并感染中的作用。
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CHB和非活性携带者的肝活检和弹性成像
对于处于“灰色区域”的患者，AASLD指南建议进行肝活检以确定纤维化和炎症的程度。尽管无活性的载体在活检中将没有/最小程度的坏死性炎症，但AASLD指南指出，这些患者在肝活检和无创纤维化测试中可能具有不同程度的纤维化。



但是，有些患者不愿进行活检，并且有可能出现抽样误差。首选的非侵入性纤维化测试是弹性成像。如果HBV DNA <2000 IU / mL且ALT升高，则应检查肝酶升高的其他原因。瞬时弹性成像（TE）在CHB患者中显示出非常好的诊断准确性（对于F2-F4期，AUROC> 0.88）。尽管费用更高，但磁共振弹性成像（MRE）可以更准确地区分CHB患者的纤维化分期（F1-F4期的AUROC> 0.96）。对于BMI> 40，TE具有可变可靠性的患者，MRE可能很有价值。 EASL指南建议对ALT正常且在TE上肝硬度测量值（LSM）为6-9 kPa的患者或ALT升高至正常上限的5倍且LSM为6- 12 kPa。



我在实践中做什么
在我的实践中，我并非常规为所有CHB患者订购qHBsAg，但我发现qHBsAg在某些情况下有助于区分无活性的携带者状态和免疫活性的HBeAg阴性的CHB。这些包括：

    ALT正常，HBV DNA维持或波动略大于2000 IU / mL（例如2200-5000 IU / mL），信息相互矛盾的患者（例如LSM低但影像学肝脏略粗）以及对肝活检有所犹豫的患者

    TE的ALT和/或HBV DNA临界升高和中度LSM升高的患者

    还有其他引起ALT升高的原因的患者，例如非酒精性脂肪性肝炎伴有临界值或HBV DNA波动

    或任何乙肝病毒DNA或ALT水平处于非活动性感染与免疫活动性HBeAg阴性CHB之间的界限的患者，他们不愿意进行肝活检

如果上述任何情况下的患者的HBsAg> 1000 IU / mL，对我而言，这暗示该患者可能不是无活性的携带者，而是具有免疫活性的HBeAg阴性CHB，并且可能具有更高的HCC和肝病进展。这将促使我决定开始抗病毒治疗和开始HCC筛查。



你的想法
您在临床实践中使用qHBsAg吗？您在什么情况下获得了qHBsAg？
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