停止核苷酸類似物治療後，白種人中的HBsAg丟失率高於亞洲人

StephenW

HBsAg loss is higher among Caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multiethnic cohort of patients with chronic hepatitis B (RETRACT-B study)

HBsAg Loss in 14% Through 4 Years After Stopping NUC

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

Mark Mascolini

Four years after people with chronic HBV infection stopped a nucleos(t)ide analog (NUC) in a 1500-person global retrospective cohort, 14% had lost HBsAg, suggesting functional cure [1]. Caucasian versus Asian race favored HBsAg loss. But three quarters of the cohort had a virologic relapse through 4 years of follow-up, and one third had an alanine aminotransferase (ALT) flare.

Losing HBsAg happens only rarely during NUC therapy. Researchers have begun evaluating stopping NUCs to assess the safety and durability of that strategy, as well as its impact on HBsAg. RETRACT-B study investigators formed an international cohort of people with chronic HBV who stopped NUC therapy from 2001 to 2020 at centers in North America, Europe, and Asia, aiming to analyze the impact of stopping on HBsAg loss and other outcomes.

To be eligible for this retrospective cohort study, people had to have undetectable HBV DNA in blood and HBeAg-negative status when stopping therapy. When NUC therapy began, they could be positive or negative for HBeAg. Participants could not be coinfected with HCV, HDV, or HIV and could not have taken interferon or pegylated interferon in the 12 months before stopping NUC therapy. Researchers used Kaplan-Meier and Cox methods to determine which factors affected off-treatment HBsAg loss or retreatment.

The 1541 cohort members averaged 53 years in age at the baseline date, when they stopped NUC therapy; 73% were men, 88% Asian, and 10% Caucasian. NUC therapy lasted a median of 3 years, 60% took entecavir when they stopped, and 29% took tenofovir disoproxil fumarate (TDF). Only 5% had cirrhosis at baseline, and HBsAg level averaged 2.6 log10 IU/mL. When NUC therapy began, 77% were negative for HBeAg. Median total follow-up stood at 17 months, and participants averaged 5 visits during follow-up.

The proportion of people who lost HBsAg rose slowly but steadily over time: 3% 1 year after NUC therapy stopped, 8% after 2 years, 12% after 3 years, and 14% after 4 years. HBsAg loss proved more frequent in people 50 or older than in younger people (18% vs 9% at 4 years, P = 0.01), in Caucasians versus Asians (41% vs 11% at 4 years, P < 0.001), and in people taking TDF versus entecavir (17% vs 12% at 4 years, P = 0.001). HBeAg status when therapy began did not affect rate of HBsAg loss.

One year after stopping their NUC, 30% needed to resume therapy. That proportion rose to 43% at 2 years, 50% at 3 years, and 56% at 4 years. Retreatment proved more likely in people 50 or older (63% vs 45% at 4 years, P < 0.001). Race, type of NUC, or HBeAg status when therapy began did not affect retreatment rate.

A multivariate Cox model identified 1 factor that independently predicted HBsAg loss and 1 that predicted retreatment, at the following hazard ratios (HR) and 95% confidence intervals (CI):

HBsAg loss
-- Caucasian vs Asian: HR 5.8, 95% CI 3.6 to 9.5, P < 0.001

Retreatment
-- Age 50 or older vs younger: HR 1.6, 95% CI 1.3 to 1.9, P < 0.001

Participant sex, NUC used, or HBeAg status at the start of therapy did not affect HBsAg loss or retreatment in these analyses.

Only one quarter of participants went 4 years off therapy without virologic relapse (HBV DNA above 2000 IU/mL): 74% had such a relapse a median of 6 months after stopping therapy. More than half, 56%, had both a virologic relapse and a biochemical relapse (ALT at least 2 times the upper limit of normal) in a median of 8 months. One third of participants had an ALT flare (at least 5 times the upper limit of normal) over a median of 10 months. Fifteen people (1%) had hepatic decompensation. Among the 12 people (0.8%) who died, 9 had a liver-related cause of death reported.

Reference
1. Hirode G, Choi HSJ, Su TH, et al. HBsAg loss is higher among Caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multiethnic cohort of patients with chronic hepatitis B (RETRACT-B study). AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 23.

StephenW

停止核苷酸類似物治療後，白種人中的HBsAg丟失率高於亞洲人：這是來自全球性的多種族慢性乙型肝炎患者群體的結果（RETRACT-B研究）

停止NUC後4年內HBsAg損失14％

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

在患有慢性HBV感染的人中，在1500人的全球回顧性研究隊列中終止了核苷酸類似物（NUC）的四年後，有14％的患者失去了HBsAg，表明其可以治愈[1]。高加索人與亞洲人的種族贊成HBsAg的丟失。但是，該隊列中有四分之三的患者在隨訪4年後出現病毒學復發，三分之一的患者出現了丙氨酸氨基轉移酶（ALT）發作。

在NUC治療期間，很少發生HBsAg丟失。研究人員已開始評估停止NUC的使用，以評估該策略的安全性和持久性及其對HBsAg的影響。 RETRACT-B研究人員組成了一個國際性隊列，研究人群為慢性HBV患者，他們於2001年至2020年在北美，歐洲和亞洲的中心停止了NUC治療，旨在分析停止服用HBsAg和其他結局的影響。

為了符合這項回顧性隊列研究的條件，人們在停止治療時必須在血液中檢測到HBV DNA且HBeAg陰性。當開始NUC治療時，它們的HBeAg可能為陽性或陰性。在停止NUC治療之前的12個月內，參與者不能合併感染HCV，HDV或HIV，也不能服用乾擾素或聚乙二醇化干擾素。研究人員使用Kaplan-Meier和Cox方法來確定哪些因素影響了治療後HBsAg的丟失或再治療。

1541名隊列成員在基線日期停止NUC治療時的平均年齡為53歲。男性73％，亞洲88％，白人10％。 NUC治療持續了3年，停止使用恩替卡韋的比例為60％，而富馬酸替諾福韋酯為29％。基線時只有5％患有肝硬化，HBsAg水平平均為2.6 log10 IU / mL。當開始NUC治療時，有77％的HBeAg陰性。平均總隨訪時間為17個月，參與者平均隨訪5次。

隨著時間的流逝，失去HBsAg的人的比例緩慢而穩定地上升：NUC治療停止1年後為3％，兩年後為8％，三年後為12％，四年後為14％。在50歲或50歲以上的人群中，HBsAg丟失的發生率高於年輕人（4歲時為18％比9％，P = 0.01），白種人與亞洲人相比（4歲時為41％對11％，P <0.001），以及服用TDF與恩替卡韋的患者（17％vs 4年時的12％，P = 0.001）。開始治療時的HBeAg狀態不影響HBsAg丟失率。

停止NUC一年後，有30％的人需要恢復治療。該比例在2年時升至43％，在3年時升至50％，在4年時升至56％。事實證明，50歲或50歲以上的人群更有可能接受再治療（63％比4歲的45％，P <0.001）。治療開始時的種族，NUC類型或HBeAg狀態不影響再治療率。

多元Cox模型在以下危險比（HR）和95％置信區間（CI）下確定了1個獨立預測HBsAg丟失的因素和1個預測再次治療的因素：

HBsAg丟失
-白人vs亞洲：HR 5.8，95％CI 3.6至9.5，P <0.001

再處理
-50歲或50歲以上的年輕人：HR 1.6，95％CI 1.3至1.9，P <0.001

在這些分析中，參加者的性別，使用的NUC或治療開始時的HBeAg狀態不影響HBsAg的丟失或重新治療。

只有四分之一的參與者在沒有病毒學復發的情況下停止治療4年（HBV DNA高於2000 IU / mL）：74％的此類復發在停止治療後的6個月中值。超過一半（56％）的病毒中毒和生化復發（ALT至少是正常上限的2倍）均在8個月的中位出現。三分之一的參與者在10個月的中位數內出現ALT發作（至少是正常上限的5倍）。十五人（1％）患有肝失代償。在死亡的12人（0.8％）中，有9人報告了與肝有關的死亡原因。

參考
1. Hirode G，Choi HSJ，Su TH等。停止核苷酸類似物治療後，白種人中的HBsAg丟失率高於亞洲人：這是來自全球性的多種族慢性乙型肝炎患者群體的結果（RETRACT-B研究）。 AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要23。