[AASLD 2012]拉米夫定（LMV）长达12年治疗

StephenW

拉米夫定（LMV）长达12年治疗
CONTROL ID:  1424619

PRESENTATION TYPE:  Oral or Poster
CURRENT CATEGORY:  Hepatitis B
CURRENT DESCRIPTORS:  I02. Treatment and Clinical Trials
TITLE:  Long-term treatment with
lamivudine (LMV) for up to 12 years: Predictive value of virus and host
related risk factors for the development of HBV resistance
AUTHORS (FIRST NAME, LAST NAME):  Annika Brodzinski1, Ulrike Mihm2,
Christoph Sarrazin2, Maria-Christina Jung3, Eckart Schott6, Balazs
Fueloep1, Beate Schlosser5, Michael Biermer4, Stephan Boehm1, Joachim
Mössner1, Thomas Berg1, Florian van Bömmel1 Institutional Author(s):
INSTITUTIONS (ALL):  1. Klinik und Poliklinik f. Gastroenterologie und
Rheumatologie, Sektion Hepatologie, Universitätsklinikum Leipzig AöR,
Leipzig, Germany. 2. Medizinische Klinik 1, Johann Wolfgang Goethe
Universität, Frankfurt/Main, Germany. 3. Gemeinschaftspraxis Leberzentrum,
München, Germany. 4. Leber- und Studienzentrum am Checkpoint, Berlin,
Germany. 5. Zentrum für Infektiologie und HIV, Vivantes
Auguste-Viktoria-Klinikum, Berlin, Germany. 6. Medizinische Klinik mit
Schwerpunkt Hepatologie und Gastroenterologie, Charité Campus
Virchow-Klinikum, Berlin, Germany.

ABSTRACT BODY:  Background: Due to a high risk of resistance of up to 76%
after 8 years, LMV is no more recommended for the treatment of chronic
hepatitis B. However, LMV is well tolerated and it is not known how many
patients eventually develop resistance during treatment beyond 8 years. Our
aim was to analyse the frequency of LMV resistance in a German multicentre
cohort and to identify factors associated with long-term response.
Methods: 227 patients with chronic HBV infection (m/f 163/64; mean age
44±3 [16–76] years, 35% HBeAg positive, mean HBV DNA level 6.6±1.6
[3-12] log10 copies(cop)/mL) were enrolled and retrospectively analysed.
All patients received LMV 100/150mg for a mean duration of 35±30 [6-146]
months and had detectable HBV DNA at baseline. During treatment, HBV DNA
levels were measured every 3-6 months (Roche Monitor HBV Test, detection
limit 400 cop/mL). Suppression of HBV DNA below the detection limit at
month 6 was defined as response. HBV resistance defined as a >1 log10
cop/mL re-increase in HBV DNA was confirmed by line probe assay (INNO-LiPa
HBV DR v2+3, Innogenetics). Results: 77 of 227 (34%) patients developed LMV
resistance. A low level of HBV DNA (<105 cop/mL) at baseline and response
at month 6 were associated with a lower probability of developing LMV
resistance (p=0.002 and p<0.001). HBeAg status at baseline, HBV genotype
and host factors as age, sex, BMI and ALT had no significant influence on
resistance development. Among HBeAg positive patients, 7 of 27 (26%) with
HBeAg loss and 18 of 41 (44%) without HBeAg loss developed LMV resistance
(p=0.01). In patients with response at month 6, HBeAg status was not
associated with the overall risk of LMV resistance (27% (HBeAg negative)
vs. 15% (HBeAg positive). However, when analyzed over time by
Kaplan-Meier-Analysis, in HBeAg negative patients with response at month 6
a risk of LMV resistance of 3%, 16%, 21%, 32%, 38%, 44% and 49% was found
after 1, 2, 3, 4, 5, 6 and 7 years of treatment. With 9 patients under
observation at this time, one more patient became resistant at month 146.
In HBeAg positive patients with response at month 6, resistance rates were
0% and 18% after 1 and 2 years. From month 16 on, no further cases of LMV
resistance were seen during the remaining observation period of 50 ± 37
[2-122] months. Conclusion: HBeAg positive and negative patients with HBV
DNA levels <105 cop/mL at baseline and response at month 6 have an equally
low risk of LMV resistance. However, HBeAg positive patients with response
at month 6 only developed resistance until month 16, while in HBeAg
negative patients with response a continuous increase in resistance
occurred up to month 146.

StephenW

背景：由于耐药高达76％的高风险
8年后，LMV是没有更多的用于治疗慢性乙型肝炎的推荐
B型肝炎，但LMV良好的耐受性，它不知道多少
患者在治疗过程中超过了8年最终产生耐药性。我们的
在德国的多中心的目的是分析频率的LMV耐药性
队列，并确定长期响应的相关因素。
方法：对227例慢性HBV感染者（男/女163/64，平均年龄
44±3 [16-76]年，35％的HBeAg阳性，平均HBV DNA水平为6.6±1.6
[3-12] log10拷贝（COP）/ mL）的患者进行回顾性分析。
所有患者均接受LMV 100/150mg的平均时间为35±30 [6-146]
个月，并有可检测到HBV DNA的基线。在治疗过程中HBV DNA
水平测定，每3-6个月（罗氏监控，检测HBV测试
限制400 COP /毫升）。抑制HBV DNA的检出限以下
响应被定义为6个月。 HBV耐药定义为A> 1 log10的
COP /毫升再次提高HBV DNA也证实了线探针法（INNO-LIPA
HBV DR v2的+3，Innogenetics公司）。结果：77 227例（34％），开发LMV
性。低水平的HBV DNA（<105 COP /毫升）在基线和响应
在6个月的概率较低与发展LMV
阻力（P = 0.002，P <0.001）。在基线HBeAg状态，HBV基因型
和宿主因素如年龄，性别，BMI和ALT没有显着的影响
耐药性的发展。在HBeAg阳性患者中，27（26％），
HBeAg消失和18 41（44％）无HBeAg消失LMV耐药

（P = 0.01）。在响应在6个月的患者，HBeAg状态
与整体风险的LMV耐药（27％（HBeAg阴性）
对15％（HBeAg阳性）。然而，当随着时间的推移的分析
Kaplan-Meier生存分析，在HBeAg阴性患者，在6个月的反应
LMV的危险性的3％，16％，21％，32％，38％，44％和49％
后，1，2，3，4，5，6和7年的治疗。随着9例下
在这个时候，一个病人的观察成为抗个月146。
在HBeAg阳性患者在6个月的反应，耐药率分别为
0％和18％后，1年和2年。从本月16日起，没有再发生LMV
阻力则见于在余下的观察期为50±37
[2-122]个月。结论：e抗原阳性与阴性患者HBV
DNA水平<105 COP /毫升在基线和6个月时的响应同样也有
低风险的LMV耐药。然而，HBeAg阳性患者的反应
仅在6个月开发的抵抗，直到本月16日，而在HBeAg
响应不断增加，阻力阴性患者
发生一个月146。

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