關於慢性乙型肝炎患者停止長期核苷酸類似療法療效的真實

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

StephenW

關於慢性乙型肝炎患者停止長期核苷酸類似療法療效的真實世界單中心經驗

如果HBeAg陰性和HBsAg低於100 IU / mL，則停止抗HBV NUC“可行”

AASLD肝臟會議數字體驗，2020年11月13日至16日

馬克·馬斯科利尼

在加拿大進行的一項回顧性單中心研究結果表明，對於慢性乙型肝炎病毒而言，終止核苷類藥物（NUCs）是可行的，並且對於HBeAg陰性且定量HBsAg（qHBsAg）低於100 IU / mL的人群來說通常是安全的[1 ]。停止NUC的47人中有6人（佔13％）由於病毒或生化爆發而不得不重啟。

進行這項研究的卡爾加里大學研究人員指出，用於慢性HBV感染的NUC治療很少導致乙型肝炎表面抗原（HBsAg）的喪失，這表明目前正在感染。結果，大多數慢性乙肝患者的治療時間延長了。卡爾加里小組指出，一些指南指出，乙型肝炎e抗原（HBeAg）陽性的人可能會在HBeAg血清轉化，6到12個月以上無法檢測到的HBV DNA以及鞏固治療後停止NUCs [2]，但是當NUCs停止時許多複發。 （HBeAg表示正在進行的HBV複製和傳播的可能性。）

由於一些證據表明，在沒有肝硬化，HBV DNA檢測不到且qHBsAg水平低於100 IU / mL的HBV患者中，可以安全地停止NUC，因此卡爾加里研究人員對他們的長期NUC患者進行了分析，旨在確定基線因素，預測的非治療耐久性。

分析涉及1337例長期服用NUC的慢性HBV感染者。研究人員確定，該組中有47人（佔3.5％）根據臨床醫生的建議停止了NUCs治療。 47名中的14名（30％）是女性，37名（78％）是東亞人，中位年齡為56歲（18至74歲）。 28人（60％）服用富馬酸替諾福韋酯（TDF），而16人（34％）服用恩替卡韋和3人（6％）拉米夫定（其中2人聯合阿德福韋）。停止治療時，所有47人均為HBeAg陰性，其中46人的HBV DNA檢測不到。肝硬度範圍為3.3至6.6 kPa（中值5.2 kPa）。

這47人中有6人（佔13％）由於病毒性耀斑（定義為2000 IU / mL以上的HBV DNA）和/或生化耀斑（定義為丙氨酸氨基轉移酶[ALT]大於上限的2倍）而不得不重新開始NUC治療。正常）。當這6個患者停止治療時，其qHBsAg水平分別為205、147、74、21、5.4和2.3。在病毒學耀斑下，他們的HBV DNA範圍為265至1.52億IU / mL（中位數4663 IU / mL），在生化耀斑下，其ALT為208、938、1467、139、828和149 IU / L。重新啟動NUC的時間為62到177天。

沒有人停止NUC治療後會出現肝功能障礙，並且在恢復治療後所有HBV DNA均被抑制（全部使用TDF）。有兩個變量將必須重新開始NUC治療的6人與未重新開始的41人區分開：（1）基線時HBeAg陰性：2（33％）重新開始，而36（88％）沒有重新開始（P = 0.01）； （2）更長的NUC持續時間：重新開始的中位時間為12.4年，而持續緩解的中位時間為6.1年（P = 0.01）。年齡，性別，種族，纖維化階段F0-F1和服用NUC不會影響復發風險。停止治療時qHBsAg與復發無關。到目前為止，有1名停止治療的人已失去HBsAg。

卡爾加里的研究人員認為，他們的發現表明，在患有慢性HBV感染，纖維化程度最低和qHBsAg水平較低的HBeAg陰性人群中，NUC戒斷“可行”。但是由於ALT耀斑可能很嚴重，因此停止NUC的人需要密切監視。

參考文獻
1. Azhari H，Frolkis A，Shaheen AA等。在慢性乙型肝炎患者中停止長期核苷酸（t）核苷酸類似療法的療效的現實世界單中心經驗。AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要24。
2.合併療法“通常需要治療至少12個月，以保持ALT水平持續正常且血清HBV DNA水平無法檢測。” Terrault NA，Bzowej NH，Chang KM等。 AASLD治療慢性乙型肝炎的指南。肝病學。 2016; 63：261-83。 doi：10.1002 / hep.28156。 https://www.aasld.org/sites/defa ... 2016-Hepatology.pdf