FRI-329 血清中的HBV RNA是持续免疫的早期预测指标 在聚乙二醇

StephenW

EASL 2018 FRI-329
HBV RNA in serum is an early predictor for sustained immune
control following treatment with pegylated interferon alfa in
patients with HBeAg negative chronic hepatitis B
M. Farag1,2, M.V. Campenhout3, F. van Boemmel4, V. Rijckborst3,
Y. Cakaloglu5, P. Ferenci6, F. Tabak7, J. Feld2, B. Hansen2,3,8, H. Janssen2.
1University of Toronto, Institute of Medical Sciences, Faculty of Medicine,
Toronto, Canada; 2Toronto General Hospital, University Health Network,
Toronto Centre for Liver Disease, Toronto, Canada; 3Erasmus Medical
Centre Rotterdam, Department of Gastroenterology & Hepatology,
Rotterdam, Netherlands; 4University Hospital Leipzig, Department of
Gastroenterology and Rheumatology, Section of Hepatology, Leipzig,
Germany; 5Istanbul University Medical School, Department of
Gastroenterohepatology, Istanbul, Turkey; 6Medical University of Vienna,
Department of Internal Medicine 3, Gastroenterology and Hepatology,
Vienna, Austria; 7Istanbul University Cerrahpasa Medical School,
Department of Infectious Diseases, Istanbul, Turkey; 8University of
Toronto, Institute of Health Policy, Management and Evaluation, Toronto,
Canada
Email: [email protected]
Background and Aims: Hepatitis B RNA (HBV RNA) is a novel serum
biomarker that is a transcriptional product of HBV covalently closed
circular DNA. In recent studies in HBeAg negative patients, kinetics of
serum HBV RNAwere shown to be associated with serologic response
following treatment with nucleos(t)ide analogues or PEG-IFN.
We aimed to study the kinetics of HBV RNA during PEG-IFN treatment
in HBeAg negative patients and its potential role as response
predictor.
Method: HBV RNA levels were retrospectively measured in stored
serum samples of 133 HBeAg-negative chronic HBV patients who
were treated in an international randomized controlled multicenter
trial (PARC study). Patients received PEG-IFN α-2a 180 mcg/week +/-
ribavirin 1000–1200 mg daily for 48 weeks. All patients were
followed until week 72. HBV RNAwas measured at week 0 (baseline),
12, 24 and 48 andweek 72 using a RACE-PCR technique (lower limit of
quantification (LLQ) 800c/ml). Response was defined as a combined
endpoint HBV DNA level below2,000 IU/ml and normalization of ALT
at week 72.
Results: The mean age was 42.2 (SD 11) years, 98 (74%) were male,
and distribution of HBV genotypes was 17/1/3/80% for A/B/C/D. The
mean (SD; range) HBV RNA at baseline was 4.0 (1.4; 1.7–7.7) log10 c/
ml and HBV RNA was < LLQ in 28 (23%) patients. No difference in
response was found between patients with or without ribavirin and
patients were thus pooled for further analyses.
At 12 and 24 weeks mean HBV RNA declined by 1.7 and 1.8 log c/ml
and HBV RNA was < LLQ in 95 (83%) and 99 (84%) patients at these
time points, respectively. At week 72, 24 patients (23%) had achieved
response. HBV RNA in the responders showed a marked decline (2.1
and 2.2 log c/ml) compared to the non-responders (1.6 and 1.6) at
weeks 12 and 2 4, respectively. None of the patients at week 12 (n =
18) and week 24 (n = 17) who exhibited an HBV RNA level above
1500c/ml (3.2 log10 c/ml) had a response at week 72 with a negative
predicative value of 100% (p = 0.01 and 0.02 respectively). However,
the positive predictive value of patients who had HBV RNA levels
below 1500c/ml (3.2 log10 c/ml) at week 12 and 24 was 28% and 27%
respectively.
Conclusion: In HBeAg-negative patients with chronic hepatitis B,
serum HBV RNA declined during PEG-IFN treatment. An HBV RNA
value above 1,500 c/ml (3.2 log10 c/mL) at week 12 was strongly
associated with nonresponse to PegIFN treatment.

StephenW

FRI-329
血清中的HBV RNA是持续免疫的早期预测指标
在聚乙二醇化干扰素α治疗后控制
HBeAg阴性慢性乙型肝炎患者
M. Farag1,2，M.V. Campenhout3，F.van Boemmel4，V.Rijckborst3，
Y.Cakaloglu5，P.Ferenci6，F.Tabak7，J.Feld2，B.Hansen2,3,8，H.Janssen2。
1多伦多大学医学院，医学院，
加拿大多伦多; 2多伦多综合医院，大学健康网，
加拿大多伦多多伦多肝病中心; 3Erasmus医疗
鹿特丹中心，胃肠病和肝病学系，
荷兰鹿特丹; 4莱比锡大学医院系
胃肠病学和风湿病学，肝病学部分，莱比锡，
德国; 5伊斯坦布尔大学医学院，系
Gastroenterohepatology，伊斯坦布尔，土耳其; 6维也纳医科大学，
内科学3，胃肠病学和肝病学，
维也纳，奥地利; 7伊斯坦布尔大学Cerrahpasa医学院，
土耳其伊斯坦布尔传染病研究所; 8大学
多伦多，卫生政策，管理和评估研究所，多伦多，
加拿大
电子邮件：[email protected]
背景和目标：乙型肝炎RNA（HBV RNA）是一种新型血清
生物标志物是HBV共价闭合的转录产物
环状DNA。在最近的研究中，HBeAg阴性患者的动力学研究
血清HBV RNA显示与血清学反应有关
用核苷酸（t）类似物或PEG-IFN处理后。
我们旨在研究PEG-IFN治疗期间HBV RNA的动力学
在HBeAg阴性患者中及其作为应答的潜在作用
预测。
方法：回顾性检测储存的HBV RNA水平
133例HBeAg阴性慢性HBV患者的血清样本
在一个国际随机对照多中心治疗
试验（PARC研究）。患者接受PEG-IFNα-2a 180 mcg /周+/-
利巴韦林1000-1200毫克，每日48周。所有患者都是
随后直到第72周。在第0周（基线）测量HBV RNA，
12,24和48周和72周使用RACE-PCR技术（下限
定量（LLQ）800c / ml）。响应被定义为一个组合
终点HBV DNA水平低于2 000 IU / ml和ALT正常化
在72周。
结果：平均年龄为42.2（SD 11）岁，男性98例（74％），
A / B / C / D的HBV基因型分布为17/1/3/80％。该
平均（SD;范围）HBV RNA在基线时为4.0（1.4; 1.7-7.7）log10 c /
ml，28例（23％）患者HBV RNA <<LLQ。在没有区别
在有或没有利巴韦林和利巴韦林的患者中发现有反应
因此将患者汇集进行进一步分析。
在第12周和第24周时，平均HBV RNA下降1.7和1.8log c / ml
其中95例（83％）和99例（84％）患者HBV RNA <<LLQ
时间点，分别。在72周时，24名患者（23％）已经达到
响应。应答者的HBV RNA显示明显下降（2.1
和2.2log c / ml）与无应答者（1.6和1.6）相比
第12周和第24周。在第12周没有患者（n =
18）和第24周（n = 17）谁显示HBV RNA水平以上
1500c / ml（3.2log10 c / ml）在72周时有反应，阴性
100％的预测值（分别为p = 0.01和0.02）。然而，
具有HBV RNA水平的患者的阳性预测值
在第12和24周时低于1500c / ml（3.2log10c / ml）为28％和27％
分别。
结论：在HBeAg阴性慢性乙型肝炎患者中，
在PEG-IFN治疗期间血清HBV RNA下降。 HBV RNA
在第12周的值高于1,500 c / ml（3.2log10 c / mL）是强烈的
与无响应PegIFN治疗有关。