Serum HBsAg kinetics in clinical prediction
[url=]Wen-Juei Jeng[/url]
, [url=]Yun-Fan Liaw[/url][url=]Correspondence information about the author Yun-Fan Liaw[/url]Email the author Yun-Fan Liaw
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
We read with great interest the review article “The role of quantitative hepatitis B surface antigen revisited” by Cornberg et al. in the Journal of Hepatology [1]. Indeed, it is a comprehensive update. However, the role of hepatitis B surface antigen (HBsAg) quantification in the prediction of spontaneous or antiviral therapy related HBsAg seroclearance and relapse after cessation of nucleos(t)ide analog (NUC) therapy was not well addressed. The studies mentioned in the review used an HBsAg level <100 IU/ml as a predictor for remote (6–10 years) HBsAg seroclearance but two studies on short-term prediction of HBsAg seroclearance within 1–3 years were not mentioned.
One longitudinal study showed that serum HBsAg level ≤200 IU/ml had a negative predictive value for HBsAg seroclearance of 100% and 92% at 1 and 3 years, respectively, and the positive predictive value increased from 36% at 1 year and 49% at 3 year to 97% and 100%, respectively if combined with a ≥1 log10 IU/ml reduction in the preceding 2 years [2]. Another large case-control study also showed that HBsAg level <200 IU/ml was predictive of HBsAg seroclearance within 3 years and a patient with HBsAg <200 IU/ml and a 0.5 log10 IU/ml HBsAg decline in the next year may predict HBsAg seroclearance in 3 years with a sensitivity of 74% and a specificity of 89.4% [3]. Obviously, prediction of spontaneous HBsAg seroclearance within a much shorter period of 1–3 years is more desirable and useful in daily clinical practice.
Stronger HBsAg decline during NUC therapy associated with higher pretherapy alanine aminotransferase (ALT) was briefly mentioned in the review. Actually, patients with pretherapy ALT over 5× upper limit of normal (ULN) showed greater HBsAg decline not only at an ALT-level dependent manner but also at an alpha-fetoprotein (AFP) level-dependent manner, in which AFP dominated over ALT as a more powerful factor for early “rapid HBsAg decline” [4]. These findings are important because “rapid HBsAg decline” >0.5 log10 IU/ml by month 6 or >1 log10 IU/ml by month 12 of NUC therapy were found to be predictors for HBsAg seroclearance [5], and HBsAg decline ≥75% by week 24 of adefovir/tenofovir therapy was also predictive for HBsAg seroclearance [6]. A most recent study further showed that hepatitis flares (ALT >5× ULN) during pegylated interferon and tenofovir combination therapy in HBeAg positive patients was associated with HBsAg decline >1 log10 by week 12, which was an independent factor for HBsAg loss [7]. More studies on this issue are ongoing.
The issue of stopping NUC therapy in HBeAg-negative patients has attracted more and more attention in recent years. Studies have shown the lower the HBsAg level at the end of NUC therapy, the less chance of clinical relapse [[8], [9], [10]]. HBsAg <100 IU/ml seems to be the best predictive level but no consensus has been reached. This is also applicable in patients with liver cirrhosis who had discontinued NUC therapy, as such patients were included in these studies [[8], [9], [10]].
In conclusion, HBsAg quantification has a wide range of clinical applications. It is anticipated that the role of HBsAg kinetics in the natural course and during antiviral therapy in patients with chronic hepatitis B will remain a hot issue to be explored. 作者: antiHBVren 时间: 2017-12-11 20:10
血清HBsAg动力学在临床预测中的应用
我们非常感兴趣地阅读Cornberg等人的评论文章“重新定量的乙肝表面抗原的作用”在“肝脏病学杂志”[1]中。事实上，这是一个全面的更新。然而，乙肝表面抗原（HBsAg）定量在预测自发或抗病毒治疗相关HBsAg血清清除和核苷（酸）类似物（NUC）治疗停止后复发的作用尚未得到很好的解决。这篇综述中提到的研究使用HBsAg水平<100 IU / ml作为偏倚（6 - 10年）HBsAg血清学清除的预测指标，但是没有提到两项在1 - 3年内短期预测HBsAg血清学清除的研究。
一项纵向研究显示，血清HBsAg水平≤200IU / ml对1年和3年HBsAg血清学清除率分别为100％和92％的阴性预测值，阳性预测值从1年的36％上升到49％如果在前2年中≥1log10 IU / ml的降低，则分别为3％〜97％和100％[2]。另一项大型病例对照研究还显示，HBsAg水平<200 IU / ml可预测3年内HBsAg血清学清除率，而HBsAg <200 IU / ml和0.5 log10 IU / ml HBsAg下一年下降的患者可预测HBsAg 3年的血清学清除率为74％，特异性为89.4％[3]。很显然，在1 - 3年的短期内预测自发性HBsAg血清学清除在日常临床实践中更为理想和有用。
在审查中简要提到了与更高的治疗前丙氨酸氨基转移酶（ALT）相关的NUC治疗期间更严重的HBsAg下降。实际上，治疗前ALT超过正常上限5倍（ULN）的患者不仅在ALT水平依赖性方面显示出更大的HBsAg下降，而且以甲胎蛋白（AFP）水平依赖性方式表现出更大的HBsAg下降，其中AFP主导ALT作为早期“快速HBsAg下降”的更强有力的因素[4]。这些发现非常重要，因为NUC治疗12个月时，“HBsAg下降”> 0.5 log10 IU / ml或> 12 log10 IU / ml被认为是HBsAg血清学清除的预测指标[5]，HBsAg下降≥75％阿德福韦/替诺福韦治疗24周也可以预测HBsAg血清学清除[6]。最近的一项研究进一步表明，HBeAg阳性患者聚乙二醇干扰素和替诺福韦联合治疗期间肝炎（ALT> 5×ULN）在第12周时与HBsAg下降> 1 log10相关，这是HBsAg消失的独立因素[7] 。有关这个问题的研究正在进行中。
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