在慢性乙型肝炎患者中停止长期核苷酸（t）类似物治疗效果

StephenW

Real world single center experience on the efficacy of stopping long term nucleos(t)ide analog therapy in patients with chronic hepatitis B.

Stopping Anti-HBV NUCs “Feasible” if HBeAg-Negative and HBsAg Below 100 IU/mL

AASLD The Liver Meeting Digital Experience, November 13-16, 2020

Mark Mascolini

Stopping nucleos(t)ides (NUCs) for chronic HBV infection proved feasible and generally safe in people negative for HBeAg and with quantitative HBsAg (qHBsAg) below 100 IU/mL, according to results of a retrospective single-center study in Canada [1]. Six of 47 people (13%) who stopped NUCs had to restart because of virologic or biochemical flares.

University of Calgary researchers who conducted this study noted that NUC therapy for chronic HBV infection rarely leads to loss of hepatitis B surface antigen (HBsAg), which indicates current infection. As a result, therapy becomes prolonged for most people with chronic HBV. The Calgary team pointed out that some guidelines say hepatitis B e antigen (HBeAg)-positive people may stop NUCs after HBeAg seroconversion, undetectable HBV DNA for more than 6 to 12 months, and consolidation therapy [2], yet many relapse when NUCs stop. (HBeAg indicates ongoing HBV replication and the possibility of transmission.)

Because some evidence suggests NUCs can be stopped safely in HBV patients without cirrhosis, with undetectable HBV DNA, and with qHBsAg levels under 100 IU/mL, the Calgary researchers analyzed that approach in their long-term NUC patients, aiming to determine baseline factors that predicted off-treatment durability.

The analysis involved 1337 people taking long-term NUCs for chronic HBV infection. The researchers determined that 47 in this group (3.5%) stopped NUCs on their clinician’s advice. Fourteen of the 47 (30%) were women, 37 (78%) were East Asian, and median age stood at 56 years (range 18 to 74). While 28 people (60%) were taking tenofovir disoproxil fumarate (TDF), 16 (34%) took entecavir and 3 (6%) lamivudine (2 of them combined with adefovir). All 47 people were HBeAg-negative when they stopped therapy, and 46 had undetectable HBV DNA. Liver stiffness ranged from 3.3 to 6.6 kPa (median 5.2 kPa).

Six of these 47 people (13%) had to restart NUC therapy because of virologic flare (defined as HBV DNA above 2000 IU/mL) and/or biochemical flare (defined as alanine aminotransferase [ALT] more than 2 times the upper limit of normal). When these 6 stopped therapy their qHBsAg levels stood at 205, 147, 74, 21, 5.4, and 2.3. At their virologic flare their HBV DNA ranged from 265 to 152 million IU/mL (median 4663 IU/mL), and at biochemical flare their ALTs were 208, 938, 1467, 139, 828, and 149 IU/L. Time to restarting NUCs ranged from 62 to 177 days.

Hepatic dysfunction developed in no one who stopped NUC therapy, and all suppressed HBV DNA when treatment resumed (all with TDF). Two variables distinguished the 6 people who had to restart NUC therapy from the 41 who did not: (1) HBeAg-negative at baseline: 2 (33%) who restarted versus 36 (88%) who did not (P = 0.01); (2) longer NUC duration: median 12.4 years in restarters versus 6.1 years in sustained responders (P = 0.01). Age, sex, ethnicity, fibrosis stage F0-F1, and NUC taken did not affect relapse risk. qHBsAg when stopping therapy did not correlate with relapse. So far, 1 person who stopped therapy has lost HBsAg.

The Calgary investigators think their findings suggest that NUC withdrawal “is feasible” in HBeAg-negative people with chronic HBV infection, minimal fibrosis, and low qHBsAg levels. But because ALT flares can be severe, people who stop NUCs need close monitoring.

References
1. Azhari H, Frolkis A, Shaheen AA, et al. Real world single center experience on the efficacy of stopping long term nucleos(t)ide analog therapy in patients with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 24.
2. Consolidation therapy “generally involves treatment for at least 12 months of persistently normal ALT levels and undetectable serum HBV DNA levels.” Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83. doi: 10.1002/hep.28156. https://www.aasld.org/sites/defa ... 2016-Hepatology.pdf

Real World Single Centre Experience on the Efficacy of Stopping Long Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B



AASLD 2020 Nov 11-16 virtual

H Azhari, AD Frolkis, AA Shaheen, H Israelson, J Pinto, SE Congly, MA Borman, AA Aspinall, LM Stinton, MG Swain, KW Burak, SS Lee, MD Sadler and CS Coffin

StephenW

在慢性乙型肝炎患者中停止长期核苷酸（t）类似物治疗效果的真实世界单中心经验。

如果HBeAg阴性和HBsAg低于100 IU / mL，则停止抗HBV NUC“可行”

AASLD肝脏会议数字体验，2020年11月13日至16日

马克·马斯科利尼

在加拿大进行的一项回顾性单中心研究结果表明，对于慢性乙型肝炎病毒而言，终止核苷类药物（NUCs）是可行的，并且对于HBeAg阴性且定量HBsAg（qHBsAg）低于100 IU / mL的人群来说通常是安全的[1 ]。停止NUC的47人中有6人（占13％）由于病毒或生化爆发而不得不重启。

进行这项研究的卡尔加里大学研究人员指出，用于慢性HBV感染的NUC治疗很少导致乙型肝炎表面抗原（HBsAg）丢失，这表明当前已感染。结果，大多数慢性乙肝患者的治疗时间延长了。卡尔加里小组指出，一些指南指出，乙型肝炎e抗原（HBeAg）阳性的人可能在HBeAg血清转化，6到12个月以上无法检测到的HBV DNA以及巩固治疗后停止NUCs [2]，但是当NUCs停止时许多复发。 （HBeAg表示正在进行的HBV复制和传播的可能性。）

由于一些证据表明，在没有肝硬化，HBV DNA检测不到且qHBsAg水平低于100 IU / mL的HBV患者中，NUCs可以安全停药，因此卡尔加里研究人员对他们的长期NUC患者进行了分析，旨在确定基线因素，预测的非治疗耐久性。

分析涉及1337例长期服用NUC的慢性HBV感染者。研究人员确定，该组中有47人（占3.5％）根据临床医生的建议停止了NUCs治疗。 47名中的14名（30％）是女性，37名（78％）是东亚人，中位年龄为56岁（18至74岁）。 28人（60％）服用富马酸替诺福韦酯（TDF），而16人（34％）服用恩替卡韦和3人（6％）拉米夫定（其中2人联合阿德福韦）。停止治疗时，所有47人均为HBeAg阴性，其中46人的HBV DNA检测不到。肝硬度范围为3.3至6.6 kPa（中值5.2 kPa）。

这47人中有6人（13％）由于病毒性耀斑（定义为2000 IU / mL以上的HBV DNA）和/或生化耀斑（定义为丙氨酸氨基转移酶[ALT]大于上限上限的2倍）而不得不重新开始NUC治疗。正常）。当这6个患者停止治疗时，其qHBsAg水平分别为205、147、74、21、5.4和2.3。在病毒学耀斑下，他们的HBV DNA范围为265至1.52亿IU / mL（中位数4663 IU / mL），在生化耀斑下，其ALT为208、938、1467、139、828和149 IU / L。重新启动NUC的时间为62到177天。

没有人停止NUC治疗后会出现肝功能障碍，并且在恢复治疗后所有HBV DNA均被抑制（全部使用TDF）。有两个变量将必须重新开始NUC治疗的6人与没有重新开始的41人区分开来：（1）基线时HBeAg阴性：2（33％）重新开始，而36（88％）没有重新开始（P = 0.01）； （2）更长的NUC持续时间：重新开始的中位时间为12.4年，而持续缓解的中位时间为6.1年（P = 0.01）。年龄，性别，种族，纤维化阶段F0-F1和服用NUC不会影响复发风险。停止治疗时qHBsAg与复发无关。到目前为止，有1名停止治疗的人已失去HBsAg。

卡尔加里的研究人员认为，他们的发现表明，在患有慢性HBV感染，纤维化最少，qHBsAg水平低的HBeAg阴性人群中，NUC戒断“可行”。但是由于ALT耀斑可能很严重，因此停止NUC的人需要密切监视。

参考文献
1. Azhari H，Frolkis A，Shaheen AA等。在慢性乙型肝炎患者中停止长期核苷酸（t）核苷酸类似疗法的疗效的现实世界单中心经验。AASLD肝脏会议数字体验，2020年11月13日至16日。摘要24。
2.合并疗法“通常需要治疗至少12个月，以保持ALT水平持续正常且血清HBV DNA水平无法检测。” Terrault NA，Bzowej NH，Chang KM等。 AASLD治疗慢性乙型肝炎的指南。肝病学。 2016; 63：261-83。 doi：10.1002 / hep.28156。 https://www.aasld.org/sites/defa ... 2016-Hepatology.pdf

停止长期使用核苷类似物治疗慢性乙型肝炎疗效的真实世界单中心经验



AASLD 2020 11月11日至16日虚拟

H Azhari，AD Frolkis，AA Shaheen，H Israelson，J Pinto，SE Con​​gly，MA Borman，AA Aspinall，LM Stinton，MG Swain，KW Burak，SS Lee，MD Sadler和CS Coffin