AASLD2014:干扰素诱导蛋白10（IP10）血清水平预测的HBsAg血清中

StephenW

1890
Interferon-inducible protein 10 (IP10) serum levels predict the decline of HBsAg serum levels in HBeAg-neg-ative chronic hepatitis B (CHBe-) patients treated with tenofovir disoproxil fumarate (TDF)
George V. Papatheodoridis1, Christos K. Triantos2, Emilia Hadziyannis3, Konstantinos Zisimopoulos2, Anastasia Georgiou1, Theodoros Voulgaris1, Jiannis Vlachogiannakos1, Vasiliki Nikolopoulou2, Spilios Manolakopoulos3;
1Academic Department of Gastroenterology, Laiko General Hospital, Athens, Greece; 2Department of Gastroenterology, University Hospital of Patras, Patras, Greece; 32nd Academic Department of Internal Medicine, Hippokratio Hospital, Athens, Greece

Background/Aim: Serum HBsAg levels are considered as a potential predictor of on-therapy and most importantly off-therapy remission in CHBe- patients treated with nucleos(t)ide ana-logue(s) (NA). We recently reported that serum IP10 levels represent a promising predictor of HBsAg decline in CHBe-patients treated with entecavir. We studied the changes and predictors of decline of HBsAg levels in patients with compensated CHBe- treated with TDF for ≥12 months.
Methods: 160 patients (M/F:117/43, mean age:56±16 years) who started TDF therapy between 2008-2012 were enrolled: 82 were NA naïve (Group A) and 78 had been exposed to other NA (lamivudine resistance: 68, telbivudine resistance: 6, other: 4) (Group B). TDF has been given for a mean of 35±18 months as monotherapy in all but 55 patients of group B who received TDF and lamivudine/telbivudine for the first 6-12 months. Stored serum samples taken before and at 6, 12, 24, 36 and 48 months after TDF onset were tested for HBsAg levels on the Architect analyzer (Abbott). In 78 patients, stored serum samples before TDF onset were tested for IP10 levels by a solid phase sandwich ELISA (BioVendor).
Results: Before TDF onset, Group A and B patients had median serum levels of ALT 78 and 36 IU/L (p<0.001), HBV DNA 5.8 and 3.4 log10 IU/mL (p<0.001) and HBsAg 3.5 and 3.2 log10 IU/mL (p=0.330), respectively. Virological remission (undetectable HBV DNA) rates were 92% at 12 months and 99% beyond 12 months, without difference between Group A and B. Compared to before TDF, HBsAg levels decreased by a median of 0.17, 032, 0.42 and 0.48 log10 IU/mL at 12, 24, 36 and 48 months, respectively (p<0.001 by paired non-parametric test for all changes). The 12-, 24-, 36- and 48-month cumulative rates of HBsAg≤100 IU/mL were 9%, 18%, 21% and 31% and of HBsAg≤1000 IU/mL were 30%, 40%, 43% and 51%, respectively. The only factor that was associated with HBsAg ≤100 or ≤1000 IU/mL was lower HBsAg level before TDF (p<0.010). The 12-, 24-, 36- and 48-month cumulative rates of >0.5 log10 HBsAg decline were 4%, 12%, 27% and 36%, respectively. HBsAg decline >0.5 log10 was significantly associated only with higher IP10 levels (p=0.005) and particularly with IP10 >350 pg/mL (RH:5.58, 95% CI: 1.87-16.65, p=0.002).
Conclusions: In both NA naïve and experienced patients with CHBe-, TDF therapy decreases serum HBsAg levels. After 4 years of therapy, HBsAg levels ≤100 or ≤1000 IU/mL can be achieved in approximately 30% and 50% of patients, particularly those with low baseline HBsAg levels. HBsAg decline is slow (>0.5 log10 in 36% of patients after 4 years) and is associated only with higher baseline serum IP10 levels.

Disclosures:

George V. Papatheodoridis - Advisory Committees or Review Panels: Merck, Novartis, Abbvie, Boerhinger, Bristol-Meyer Squibb, Gilead, Roche, Janssen, GlaxoSmith Kleine; Grant/Research Support: Roche, Gilead, Bristol-Meyer Squibb, Abbvie, Janssen; Speaking and Teaching: Merck, Bristol-Meyer Squibb, Gilead, Roche, Janssen, Abbvie

Spilios Manolakopoulos - Advisory Committees or Review Panels: NOVARTIS, ROCHE, MSD, BMS, GILEAD; Consulting: ROCHE, GILEAD, BMS; Speaking and

Teaching: MSD, GILEAD, BMS

The following people have nothing to disclose: Christos K. Triantos, Emilia Hadzi-yannis, Konstantinos Zisimopoulos, Anastasia Georgiou, Theodoros Voulgaris, Jiannis Vlachogiannakos, Vasiliki Nikolopoulou

StephenW

1890
干扰素诱导蛋白10（IP10）血清水平预测的HBsAg血清中的HBeAg-NEG-ative慢性乙型肝炎的下降与富马酸替诺福韦酯（CHBe-）治疗的患者（TDF）
乔治五世Papatheodoridis1，克里斯托K. Triantos2，艾米利亚Hadziyannis3，康斯坦丁Zisimopoulos2，阿纳斯塔西娅Georgiou1，塞奥佐罗斯Voulgaris1，Jiannis Vlachogiannakos1，瓦西莉奇Nikolopoulou2，Spilios Manolakopoulos3;
消化内科，Laiko总医院，雅典，希腊1Academic部;教研室消化内科，帕特雷，希腊帕特雷大学医院;内科，Hippokratio医院，希腊雅典第32届学术部

背景/目的：血清HBsAg水平被认为是一个潜在的预测值上，治疗和最重要的关断治疗缓解与核苷（酸）的ide语录-Logue的（多个）（NA）的治疗CHBe-患者。我们最近报道，血清IP10级别代表的HBsAg下降CHBE，患者恩替卡韦治疗的有前途的指标。我们研究了代偿CHBe-治疗TDF为≥12个月的变化和HBsAg水平下降的预测患者。
方法：对160例（男/女：四十三分之一百十七，平均年龄56±16岁）谁开始2008-2012年间TDF治疗的患者入选：82人NA天真（A组）和78已经接触过其他NA（拉米夫定电阻：68，替比夫定耐药：6，其他：4）（B组）。 TDF已经给出了平均35±18个月单药治疗，但在所有55例B组谁收到TDF和拉米夫定/替比夫定为第6-12个月。前和6，12，24，36和48个月内拍摄存储的血清样本TDF发生后进行了测试HBsAg水平的建筑师仪（雅培）。在78例患者，TDF发病前存储的血清样品通过固相夹心ELISA（BioVendor）进行了测试IP10水平。
结果：TDF来临前，A，B组患者ALT78和36 IU/ L（P <0.001），HBV DNA5.8和3.4日志10国际单位/毫升（P <0.001），乙肝表面抗原3.5和3.2 log10的IU的平均血清水平/ mL的（p值=0.330），分别。病毒学缓解（检测不到HBV DNA）率分别为92％，在12个月和12个月后99％，无A组和B之间的差异相比之前TDF，HBsAg水平下降了0.17，032，0.42和0.48 log10的IU的中位数/毫升，在12，24，36和48月，分别为（P <0.001配对的非参数检验的所有更改）。 HBsAg≤100国际单位/毫升的12-，24-，36-48个月及累积率分别为9％，18％，21％和31％和HBsAg≤1000国际单位/毫升的分别为30％，40％，43 ％和51％之间。这与乙肝表面抗原≤100或≤1000IU/ mL的相关的唯一因素是TDF以前低的HBsAg水平（p<0.010）。中>0.5 log10的乙肝表面抗原下降12，24，36-48个月和累计率分别为4％，12％，27％和36％，分别。乙肝表面抗原下降>0.5 log10的只有更高级别IP10（P=0.005），尤其是IP10>350微克/ mL的显著关联（RH：5.58，95％CI：1.87-16.65，P =0.002）。
结论：在这两个NA天真和经验丰富的患者CHBe-，TDF治疗降低血清HBsAg水平。经过4年的治疗，HBsAg水平≤100或≤1000国际单位/毫升，可以在达到约30％和50％的患者，特别是那些具有低基线HBsAg水平。 HBsAg的下降是缓慢的（>0.5 log10的患者36％后，4岁），并且只具有更高的基线血清IP10级别相关联。

披露：

乔治五世Papatheodoridis - 咨询委员会或审查小组：默克，诺华，Abbvie，Boerhinger，百迈耶施贵宝，Gilead公司，罗氏，杨森，GlaxoSmith克莱;格兰特/研究支持：罗氏公司，Gilead公司，百迈耶施贵宝，Abbvie，扬森;口语和教学：默克，百迈耶施贵宝，Gilead公司，罗氏，杨森，Abbvie

Spilios Manolakopoulos - 咨询委员会或审查小组：诺华，罗氏，MSD，BMS基列;咨询：罗氏，基列BMS;说起和

教学：MSD，基列BMS

下面的人都没有透露：克里斯托K. Triantos，艾米利亚Hadzi - 雅尼斯，康斯坦丁Zisimopoulos，阿纳斯塔西娅乔治乌，塞奥佐罗斯Voulgaris，Jiannis Vlachogiannakos，瓦西莉奇Nikolopoulou