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2026年欧洲肝病学会年会（EASL 2026）即将于2025年5月27日-30日在西班牙•巴塞罗那正式开幕。作为全球肝病学领域的学术盛会，本届大会将汇聚国际顶尖专家学者，共同探讨肝病学、胃肠病学、移植外科及传染病学等领域的最新研究进展与临床实践突破。

大会设置前沿学术报告、高互动性研讨会及专题论坛，为与会者提供深度交流与专业提升的高端平台。为及时传递大会精华内容，肝胆相照平台将全程跟踪报道，本篇精选慢性乙型肝炎领域热点研究进行整理，以传递大会的最新动态和精彩看点。

研究一 WED-588

在接受300 mg pevifoscorvir sodium单药治疗96周后，HBeAg阳性慢性乙型肝炎患者在≥6个月随访期间HBV抗原水平持续下降

Sustained reduction of HBV antigen levels at ≥6 months follow-up in HBeAg-positive participants with chronic hepatitis B infection after 96 weeks of 300 mg pevifoscorvir sodium monotherapy

Authors：

Lung Yi Loey Mak、Andreas Jekle、Mark Anderson、Sushmita Chanda、Lillian Adame、Tiffany Fortney、Heleen Roose、Lawrence Blatt、Rene Geissler、Min Wu、Kha Le、Gavin Cloherty、Tse-I Lin、Man-Fung Yuen

▼ 背景与目的

Pevifoscorvir sodium（pevy，ALG-000184）是新型 E 型衣壳组装调节剂（CAM-E）ALG-001075 的前药。在I期临床研究 ALG-000184-201（NCT04536337）中，接受每日一次口服 300 mg pevy治疗96周的慢性乙型肝炎病毒感染患者，表现出对HBV DNA、HBV RNA以及病毒抗原的强效抑制作用。在pevy治疗结束（EOT）后，患者继续接受恩替卡韦（ETV）治疗，并在为期8周的随访期间维持了这种抗病毒效果。本研究进一步报告了在接受 ETV 治疗期间，24-48 周长期随访（LFU）中的持续抗病毒效果。

Pevifoscorvir sodium (pevy, ALG-000184) is a prodrug of ALG-001075, a novel Type E Capsid Assembly Modulator (CAM-E). In the Phase 1 study ALG-000184-201 (NCT04536337), pevy demonstrated potent on-treatment suppression of HBV DNA, RNA, and viral antigens in participants with chronic hepatitis B virus infection who received oral once-daily 300 mg pevy for 96 weeks. After the end of pevy treatment (EOT), these antiviral effects were sustained during an 8-week follow-up (FU) period on entecavir (ETV). Here, we report the sustained antiviral effect during long-term follow-up (LFU) of 24–48 weeks on ETV.

▼ 方法

在第四部分B队列中，10名HBeAg阳性受试者中的9名，于完成96周 300 mg pevy 单药治疗后，接受了≥24周的单药恩替卡韦随访，以评估HBV抗原变化。

研究采用 Roche Elecsys HBsAg II 检测试剂及Elecsys HBeAg定量检测方法测定定量HBsAg和HBeAg。HBV RNA采用Abbott Diagnostics仅供研究使用（RUO）的RealTimeHBV RNA v2.0方法检测。HBcAg、P-HBcAg及HBsAg各亚型则采用Abbott Diagnostics原型RUO方法检测，并以signal/cut-off ratio（S/CO）表示结果。

Nine of ten HBeAg-positive participants in Part 4 Cohort B were evaluated for HBV antigen changes during ≥24 weeks of ETV-only follow-up after completing 96 weeks of 300 mg pevy monotherapy. Quantitative HBsAg and HBeAg were measured using Roche Elecsys HBsAg II assay and Elecsys HBeAg quant assay. HBV RNA was measured using the Research Use Only (RUO) RealTime HBV RNA v2.0 assay (Abbott Diagnostics). HBcAg, P-HBcAg, and HBsAg isoforms were measured using prototype RUO assays and expressed as signal/cut-off ratio (S/CO).

▼ 结果

在pevy治疗期间，HBsAg中位水平下降了1.07log10IU/mL，并且这种下降在长期随访期间得以持续维持。治疗结束时（EOT）HBsAg中位水平为3.38log10IU/mL，而长期随访期间为3.30log10IU/mL，均明显低于基线中位水平4.31log10IU/mL。同样，在pevy治疗期间观察到的HBeAg降低，也在长期随访阶段持续存在。

HBV RNA及P-HBcAg在pevy治疗期间显著下降，而在长期随访阶段则出现部分回升，这与pevy和恩替卡韦各自的作用机制相符。长期随访期间，9名受试者中有5名HBV DNA水平持续低于10IU/mL，其余4名受试者则出现轻度升高，分别为11.1、26.8、40.2和364IU/mL。

在pevy单药治疗结束时，总HBs、MHBs及LHBs的中位降幅分别为0.40、1.03及1.38log10 S/CO，提示pevy对所有HBsAg亚型均具有抑制作用。LHBs的下降幅度大于总HBs，提示pevy主要作用于来源于cccDNA的HBsAg，而残余HBsAg可能主要来源于整合HBV DNA。

Median HBsAg levels declined by 1.07 log10 IU/mL during pevy treatment, and this reduction was sustained during LFU. Median HBsAg levels were 3.38 log10 IU/mL at EOT and 3.30 log10 IU/mL during LFU, both below the median baseline level of 4.31 log10 IU/mL. Similarly, reductions in HBeAg observed during pevy treatment were sustained during LFU.

HBV RNA and P-HBcAg markedly decreased during pevy treatment, followed by partial increases during LFU, consistent with the mechanisms of pevy and ETV, respectively. HBV DNA remained <10 IU/mL in 5/9 participants during LFU, while the remaining four participants showed minor increases to 11.1, 26.8, 40.2, and 364 IU/mL.

The median decline of total HBs, MHBs, and LHBs at the end of pevy monotherapy was 0.40, 1.03, and 1.38 log10 S/CO, respectively, suggesting activity against all HBsAg isoforms. Greater reductions in LHBs compared with total HBs suggest that pevy acts predominantly on cccDNA-derived HBsAg, while residual HBsAg may largely originate from integrated HBV DNA.

▼ 结论

接受300mg pevy单药治疗96周后，可观察到对HBV病毒抗原的显著抑制作用，提示cccDNA储存池减少。在HBeAg阳性的慢性乙型肝炎患者中，这种抗病毒作用在接受≥24周恩替卡韦随访期间仍可持续维持。

Potent antiviral effects on viral antigens were observed after 96 weeks of 300 mg oral pevy monotherapy, indicating reduction of the cccDNA pool. These antiviral effects were sustained during ≥24 weeks of ETV follow-up in HBeAg-positive participants with chronic hepatitis B virus infection.

研究二 OS-068-YI

新版EASL对HBeAg阴性慢性乙型肝炎病毒感染的治疗适应证可减少“灰区”患者，并更符合真实世界临床实践

The new EASL treatment indications for HBeAg-negative chronic hepatitis B virus infection reduce grey-zone patients and reflect better routine clinical practice

Authors：

Margarita Papatheodoridi, Sofia Paraskevopoulou, Panagiota Ioannidou, Paraskevi Fytili, Alkistis Maria Papatheodoridi, Stratigoula Sakellariou, Evangelos Cholongitas, Ioannis Vlachogiannakos, George Papatheodoridis

▼ 背景与目的

2025年EASL HBV临床实践指南（CPGs）扩大了HBeAg阴性慢性HBV（CHBVe-）患者的治疗适应证（TxI），推动对“灰区（grey-zone，GZ）”患者更早启动治疗，但其在真实世界中的应用情况尚不明确。本研究旨在评估：2025年新版EASL治疗适应证与2017年版相比，在灰区HBeAg阴性慢乙肝患者中的适用情况，以及这些新标准与近年来临床实践中治疗启动之间的关系。

The 2025 EASL HBV clinical practice guidelines (CPGs) expand treatment indications (TxI) for HBeAg-negative chronic HBV (CHBVe-) patients, promoting earlier treatment initiation in grey-zone (GZ) cases, but their real-life implementation is unknown. We assessed how the 2025 TxI compared to the 2017 EASL TxI apply in our GZ CHBVe- patients and how they are associated with treatment initiation in CHBVe- in clinical practice over recent years.

▼ 方法

研究纳入2010–2019年期间至少随访1次的HBeAg阴性慢性HBV感染患者，且根据2017年EASL指南，基于基线ALT/HBV DNA水平（HBV DNA>20,000IU/ml且ALT>2×ULN）尚不符合治疗适应证。合并病毒共感染、免疫抑制、失代偿、肝细胞癌（HCC）、酒精滥用或其他肝损伤患者均被排除。研究收集预设病例报告表（CRF）中的相关参数。在第1年内无治疗适应证患者中，持续ALT≤ULN且HBV DNA<2000IU/ml者定义为典型HBeAg阴性慢性感染（CIe-）患者，其余不符合典型CHBVe-定义者归为灰区（GZ）患者。2017年旧版治疗适应证包括：a）HBV DNA>20,000IU/ml且ALT>2×ULN；b）HBV DNA≥2000IU/ml且Ishak分期（F）3–4或肝脏硬度值（LS）在ALT≤/>ULN情况下分别为9.1–12/12.1–15kPa；c）存在HBV DNA且F5–6或LS>12/>15kPa。2025年新版治疗适应证包括：A）存在HBV DNA且LS>8kPa或F≥4；B）HBV DNA≥2000IU/ml且ALT>ULN或LS7.1–8kPa或F3。

All CHBVe- patients with ≥1 visit between 2010 and 2019 were included if they had no TxI by the 2017 CPGs based on baseline ALT/HBV DNA defined as HBV DNA >20,000 IU/ml and ALT >2 × ULN. Patients with coinfection, immunosuppression, decompensation or HCC, alcohol abuse or other liver injury were excluded. Parameters based on a predefined CRF were collected. Among patients without TxI during year-1, typical HBeAg-negative chronic infection (CIe-) patients were defined as those with persistently ALT ≤ULN and HBV DNA <2000 IU/ml, while GZ patients were considered those who did not fulfill the typical CHBVe- definition. Former (2017) TxI were: a) HBV DNA >20,000 and ALT >2 × ULN, b) HBV DNA ≥2000 and Ishak-stage (F) 3–4 or liver stiffness (LS) 9.1–12/12.1–15 kPa in case of ALT ≤/>ULN, or c) detectable HBV DNA and F5–6 or LS >12/>15 kPa in case of ALT ≤/>ULN. New (2025) TxI were: A) detectable HBV DNA and LS >8 kPa or F≥4, or B) HBV DNA ≥2000 and ALT >ULN or LS 7.1–8 kPa or F3.

▼ 结果

在2012例慢性HBV患者中，共有1501例（75%）纳入分析，其中男性占60%，平均年龄44±15岁，BMI为26±4kg/m²，平均随访时间6.0±4.6年。根据2017年与2025年EASL指南标准：典型HBeAg阴性慢性感染患者（CIe-）分别为679例（45%）和660例（44%）；灰区患者分别为577例（38%）和297例（20%）；符合治疗适应证患者分别为245例（16%）和544例（36%）。其中，2025年新增治疗适应证包括A类259例、B类285例。

第1年内，新版（2025）治疗适应证覆盖了19例（2.8%）原CIe-患者、280例（48.5%）原灰区患者以及全部145例原符合2017指南治疗适应证患者。而在仍不符合新版治疗适应证的297例原灰区患者中，238例（80%）为HBV DNA≥2000IU/ml但ALT≤ULN，59例（20%）为ALT>ULN但HBV DNA<2000，且上述患者LS均≤7kPa。第1年内，544例符合新版治疗适应证患者中有366例（67%）启动治疗；297例新版灰区患者中仅34例（11.4%）接受治疗；660例新版CIe-患者中仅9例（1.4%）接受治疗（p<0.001）。符合新版治疗适应证患者的1/3/5年治疗启动率分别为67%、77%和85%，而不符合新版治疗适应证患者的对应比例仅为4.5%、9%和16%（log-rank，p<0.001）。

Of 2012 chronic HBV patients, 1501 (75%) (males 60%, mean age 44 ± 15 years, BMI 26 ± 4 kg/m², follow-up 6.0 ± 4.6 years) were included. Using 2017 vs 2025 EASL CPGs, 679 (45%) vs 660 (44%) were CIe-, 577 (38%) vs 297 (20%) were GZ, and 245 (16%) vs 544 (36%) were patients with TxI (A: 259, B: 285), respectively. New (2025) TxI during year-1 were met by 19 (2.8%) former CIe- patients, 280 (48.5%) former GZ patients, and all 145 patients with 2017 TxI. Of 297 former GZ patients without new TxI, 238 (80%) had HBV DNA ≥2000 but ALT ≤ULN and 59 (20%) had ALT >ULN but HBV DNA <2000 (all LS ≤7 kPa). Therapy during year-1 was initiated in 366/544 (67%) patients with new TxI, 34/297 (11.4%) new GZ patients, and 9/660 (1.4%) new CIe- patients (p <0.001). The 1-/3-/5-year treatment initiation rates were 67/77/85% in patients with new TxI as well as 4.5/9/16% in patients without new TxI within year-1 (log-rank, p <0.001).

▼ 结论

2025年EASL新版治疗适应证可将HBeAg阴性慢乙肝灰区患者比例减少约一半，并且更能反映过去15年真实世界中的临床治疗策略。新版标准能够识别出大多数临床医生已经倾向于提前启动治疗的患者群体。

The EASL 2025 TxI reduce by half the GZ CHBVe- patients and better reflect treatment policies in routine clinical practice over the last 15 years, identifying the majority of patients clinicians are already more likely to treat.

研究三 OS-070-YI

慢性乙型肝炎患者中Peg-IFN加用治疗与核苷（酸）类似物停药的比较-两项全球队列研究（RETRACT-B与PROSPER）的合并分析

Peg-IFN add-on versus nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B – a pooled analysis of two global cohorts (RETRACT-B and PROSPER studies)

Authors：

Edo J. Dongelmans, Grishma Hirode, Florian van Bömmel, Rachel Wen-Juei Jeng, Rong-Nan Chien, Chien-Hung Chen, Tung-Hung Su, Jia-Horng Kao, Wai-Kay Seto, Lesley Patmore, Lilian Liang, Shao-wen Jiang, Dag Henrik Reikvam, Marte Holmberg, Seng Gee Lim, Fabien Zoulim, Arno Furquim d’Almeida, Scott K. Fung, Margarita Papatheodoridi, Benjamin Maasoumy, Bettina E. Hansen, Richard Post, Anna Pocurull Aparicio, Yuxian Huang, Jose A. Carrión, Norah Terrault, Marc Ghany, Fabrice Carrat, Nathalie Ganne-Carrié, Asgeir Johannessen, Thomas Vanwolleghem, Sabela Lens, Teresa Broquetas, Qiankun Hu, Markus Cornberg, Man-Fung Yuen, Grace Wong, George Papatheodoridis, Thomas Berg, Marc Bourliere, Qing Xie, Yao-Chun (Holden) Hsu, Jordan J. Feld, Harry L.A. Janssen, Milan J. Sonneveld

▼ 背景与目的

对于长期接受核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者，停用NA治疗以及加用聚乙二醇干扰素（peg-IFN）均被认为是提高HBsAg清除率的重要策略。然而，目前尚不清楚哪一种策略更具优势。

Both nucleo(s)tide analogue (NA) withdrawal and pegylated-interferon (peg-IFN) add-on are strategies to increase HBsAg loss rates in chronic hepatitis B patients on long-term NA therapy. It remains unclear which strategy is superior.

▼ 方法

研究者利用两项全球队列研究的个体患者数据进行了比较分析：（1）RETRACT-B队列，纳入停用NA治疗的患者；（2）PROSPER队列，纳入在NA基础上加用48周peg-IFN治疗的患者。研究主要终点为停用NA或开始peg-IFN加用治疗后2年内累计HBsAg清除率（Kaplan-Meier法）；次要终点包括ALT flare（ALT≥5×ULN）。研究进一步采用IPTW（逆概率加权）方法进行平衡分析，以验证结果的稳健性，并分别在整体人群及不同种族中进行分层分析。

We compared HBsAg loss rates in HBeAg-negative patients who stopped NA therapy with patients who received peg-IFN add-on using individual participant data from two global cohorts: (1) RETRACT-B, including patients who withdrew NA therapy and, (2) PROSPER, which studied NA-treated patients allocated to 48 weeks of peg-IFN add-on. The primary outcome was the cumulative HBsAg loss rate at 2 years after NA-stop or start of peg-IFN add-on (Kaplan-Meier method). Secondary outcome included ALT-flares (≥5 × ULN). Robustness of the findings was subsequently confirmed after IPTW balancing. Analyses were performed in the overall population and stratified by ethnicity.

▼ 结果

研究共纳入2,095例患者，其中停用NA组1,772例，peg-IFN加用组323例。与停药组相比，peg-IFN 加用组患者年龄更轻（48 vs 52岁，p<0.001）、男性比例更高（83% vs 72%，p<0.001）、非亚洲人比例更高（38% vs 19%，p<0.001），且基线ALT更高（26 vs 23，p=0.002）。两组在基线HBsAg水平（2.8 vs 2.7 log10 IU/mL，p = 0.30）、NA 治疗时间（4.3 vs 3.1 年，p = 0.97）以及肝硬化比例（8% vs 11%，p = 0.10）方面相似。

总体来看，peg-IFN加用组的2年累计HBsAg清除率显著高于停药组（16% vs 5%，p <0.001；IPTW 后 13% vs 5%，p <0.001）。这一优势在亚洲患者中尤为明显（20% vs 3%，p <0.001；IPTW后13% vs 3%，p <0.001），但在非亚洲患者中则无显著差异（9% vs 13%，p = 0.37；IPTW 后 8% vs 12%，p = 0.54）。

对于基线HBsAg<1,000IU/mL的患者，结果同样一致：亚洲患者中，peg-IFN加用治疗的HBsAg清除率显著高于停药组（30% vs 5%，p <0.001；IPTW 后 20% vs 5%，p <0.001）；而在非亚洲患者中，两种策略差异不显著（19% vs 33%，p = 0.13；IPTW 后 27% vs 35%，p = 0.68）。

ALT flare在停用NA后更为常见（24% vs. 6%，p <0.001；IPTW后23% vs. 5%，p <0.001），这一现象在亚洲患者（24% vs. 7%，p <0.001;IPTW后24 vs. 5%,p<0.001）及非亚洲患者（22% vs. 6%，p <0.001; IPTW后21 vs. 3%,p=0.016）中均一致存在。

In total, 2,095 patients were included (NA-stop: n = 1,772; peg-IFN add-on: n = 323). In comparison to NA-stop, peg-IFN treated patients were younger (48 vs. 52 years, p <0.001), more often male (83 vs. 72%, p <0.001), non-Asian (38 vs. 19%, p <0.001), and had higher baseline ALT (26 vs. 23, p = 0.002). Baseline HBsAg (2.8 vs. 2.7 log10 IU/mL, p = 0.30), duration of NA therapy (4.3 vs. 3.1 years, p = 0.97) and patients with cirrhosis (8 vs. 11%, p = 0.10) were similar.

The cumulative 2-year HBsAg loss rate was higher for patients treated with peg-IFN add-on vs. NA-stop (16 vs. 5%, p <0.001; IPTW: 13 vs. 5%, p <0.001). Importantly, the superiority of peg-IFN add-on was apparent in Asians (20 vs. 3%, p <0.001; IPTW: 13 vs. 3%, p <0.001), but not in non-Asians (9 vs. 13%, p = 0.37; IPTW: 8 vs. 12%, p = 0.54).

Results were consistent for patients with baseline HBsAg <1,000 IU/mL, with higher HBsAg loss rates observed with peg-IFN add-on vs. NA-stop in Asians (30 vs. 5%, p <0.001; IPTW: 20 vs. 5%, p <0.001), but not in non-Asians (19 vs. 33%, p = 0.13; IPTW: 27 vs. 35%, p = 0.68).

ALT-flares were more common after NA-stop (24 vs. 6%, p <0.001; IPTW: 23 vs. 5%, p <0.001), being consistent in Asian (24 vs. 7%, p <0.001; IPTW: 24 vs. 5%, p <0.001) and non-Asian patients (22 vs. 6%, p <0.001; IPTW: 21 vs. 3%, p = 0.016).

▼ 结论

对于亚洲慢性乙型肝炎患者，与单纯停用NA治疗相比，加用peg-IFN可获得更高的HBsAg清除率；而在非亚洲患者中，两种策略疗效相似。该研究为长期接受NA治疗患者如何个体化选择提高HBsAg清除率的最佳策略提供了重要依据。

Peg-IFN add-on resulted in higher HBsAg loss rates when compared to NA withdrawal in Asian patients, while responses were similar in non-Asians. These findings pave the way for personalised decision-making on the optimal strategy to increase HBsAg loss rates in patients on NA therapy.