EASL2015:病毒复制的长期持续抑制 关联与低HBsAg水平的患者 慢

StephenW

P0654
LONG-TERM SUSTAINED SUPPRESSION OF VIRAL REPLICATION
IS ASSOCIATED WITH LOW HBsAg LEVELS IN PATIENTS WITH
CHRONIC HEPATITIS B (CHB) TREATED WITH NUCLEOS(T)IDE
ANALOGUES (NUCS)
E. Sua´ rez1, M. Prieto2, C.A. Navascue´ s3, E. Hoyas1, V. Hontagas2,
M.L. Gonz´ alez-Gieguez3, B. Figueruela1, M. Garc´ıa-Eliz2,
M. Rodr´ıguez3. 1Gastroenterology, Hospital Universitario Valme,
Sevilla, 2Hepatology, Hospital Universitario Polit´ecnico La Fe, Valencia,
3Hepatology, Hospital Central Asturias, Oviedo, Spain
E-mail: [email protected]
Background and Aims: The ideal endpoint of CHB treatment is loss
of HBsAg but this is rarely achieved in patients treated with NUCs.
The aims of the study were to assess long-term HBsAg levels in
patients treated with NUCs and to identify factors associated with
low HBsAg levels.
Methods: The study population consisted of 224 patients treated
with NUCs for at least 1 yr. HBV-DNA levels were assessed
by a TR-PCR assay and HBsAg levels by an ELISA quantitative
method. Low HBsAg levels were defined as HBsAg <1000 IU/mL.
Sustained virological response time (SVRT) was defined as the time
elapsed between confirmed negativization of HBV-DNA and the last
available HBV-DNA result.
Results: 70% of patients were male with mean age of 44.7±12 yrs;
most of them had genotype D (59%) or A (30%), 28% were HBeAg+
and 22% had cirrhosis at baseline. Mean pre-treatment HBV-DNA
levels were 6.08±1.47 log IU/mL and mean baseline ALT levels were
129±159 U/mL. First line of treatment consisted of first generation
NUCs in 50% of the cases and second generation NUCs in the
remaining 50%. Median duration of treatment and SVRT were
6 yrs (range:1–15 yrs) and 4.6 yrs (range:0–12.6 yrs), respectively.
31% patients developed resistance to some NUC during treatment.
At the last follow-up, HBV-DNA was negative in 97% of the patients
and median HBsAg levels were 1606 IU/mL (range:1–21000 IU/mL).
Last HBsAg levels were <1000 IU/mL and <100 IU/mL in 40.2%
and 12.5% of the patients, respectively. Mean HBsAg levels were
4268±4293 IU/mL in patients treated <5 yrs, 2640±3244 IU/mL in
those treated 5–10 yrs, and 1480±2217 IU/mL in those treated
>10 yrs (p = 0.007 between <5 yrs and 5–10 yrs; p = 0.01 between
5–10 yrs and >10 yrs). Variables associated with low HBsAg levels
in the univariate analysis: male sex (p = 0.001), development
of NUC resistance (p = 0.01), baseline HBV-DNA <5.8 log IU/mL
(p = 0.01), treatment for more than 5 yrs (p < 0.001), and SVRT
>4 yrs (p < 0.001). Male sex (OR 2.06, 95% CI: 1.05–4.02, p = 0.01),
baseline HBV-DNA <5.8 log IU/mL (OR 2.06, 95% CI: 1.05–4.02,
p = 0.01), and SVRT >4 yrs (OR 2.91, 95% CI: 1.43–5.89, p = 0.01) were
independently associated with low HBsAg levels in the multivariate
analysis.
Conclusions: Long-term treatment with NUCs achieves suppression
of viral replication in nearly all patients with CHB and low
HBsAg levels in a significant proportion of them. This sustained
suppression of viral replication seems to be playing a significant
role in obtaining low HBsAg levels with its potential clinical
implications.

StephenW

P0654
病毒复制的长期持续抑制
关联与低HBsAg水平的患者
慢性乙型肝炎（CHB）治疗核苷（酸）IDE
类似物（NUCS）
E. Sua' rez1，M. Prieto2，C.A. Navascue' S3，E Hoyas1，五Hontagas2，
M.L. Gonz' alez-Gieguez3，B. Figueruela1，M.Garc'ıa-Eliz2，
M.Rodr'ıguez3。 1Gastroenterology，医院Universitario Valme，
塞维利亚，2Hepatology，医院Universitario Polit'ecnico拉铁，瓦伦西亚，
3Hepatology，医院中央阿斯图里亚斯，西班牙奥维耶多
电子信箱：[email protected]
背景和目的：慢性乙肝治疗的理想终点是损失
的HBsAg但这与NUCs治疗的患者很少实现。
这项研究的目的是评估在长期HBsAg水平
与NUCs并以识别与相关联的因子治疗的患者
低HBsAg水平。
方法：研究对象包括224治疗患者
与NUCs至少1年。 HBV-DNA水平进行了评估
通过用ELISA一个定量TR-PCR检测及HBsAg水平
方法。低HBsAg水平被定义为的HBsAg <1000 IU /毫升。
持续病毒学应答时间（SVRT）定义为时间
HBV-DNA和最后的确认negativization之间经过
可HBV-DNA的结果。
结果：70％的患者为男性，44.7±12岁，平均年龄;
他们大多有D型（59％）或A（30％），28％为HBeAg +
和22％患有肝硬化在基准。平均治疗前HBV-DNA
水平分别为6.08±1.47 IU登录/ mL和平均基线ALT水平
129±159 U / mL的。治疗第一线包括第一代
在的情况下，50％的NUCs并且在第二代NUCs
剩余的50％。治疗和SVRT的时间中位数分别为
6年（范围：1-15岁）和4.6岁（范围：0-12.6岁），分别。
31％的患者产生了抗药性一些NUC治疗期间。
在最后一次随访，HBV-DNA为阴性的患者97％
和中位数HBsAg水平分别为1606 IU /毫升（范围：1-21000 IU /毫升）。
最后HBsAg水平分别为<1000 IU / mL和<100国际单位/毫升的40.2％
的患者中，分别和12.5％。平均HBsAg水平分别为
4268±4293单位/ mL的治疗的患者<5年，2640±3244单位/ mL的
这些处理过的5-10岁，和1480±2217单位/ mL的那些处理
> 10岁（P = 0.007 <5岁和5-10岁之间;之间P = 0.01
5-10岁或> 10岁）。低HBsAg水平相关的变量
在单因素分析：男性（P = 0.001），发展
NUC电阻（p值= 0.01），基线HBV-DNA <5.8登录国际单位/毫升
（p值= 0.01），治疗超过5年（P <0.001），和SVRT
> 4年（P <0.001）。男性（OR 2.06，95％CI：1.05-4.02，P = 0.01），
基线HBV-DNA <5.8 IU登录/毫升（OR 2.06，95％CI：1.05-4.02，
P = 0.01），以及SVRT> 4年（OR 2.91，95％CI：1.43-5.89，P = 0.01）分别为
低HBsAg水平在多变量独立相关
分析。
结论：与NUCs长期治疗达到抑制
病毒复制几乎所有慢性乙肝患者和低
HBsAg水平在其中的一个显著比例。这种持续
抑制病毒复制，似乎被打显著
在获得低HBsAg水平，其潜在的临床作用
影响。

君看一叶舟

意思就是说抑制病毒对所有慢性病人有效，但对低水平的HBsAG更显著