非肝硬化 HBeAg 阴性慢性乙型肝炎患者停止治疗后的肝细胞癌

StephenW

非肝硬化 HBeAg 阴性慢性乙型肝炎患者停止治疗后的肝细胞癌：一项多中心队列研究
Margarita Papatheodoridi 1 2 , Tung-Hung Su 3 , Emilia Hadziyannis 4 , Chun-Hsun Liao 3 , Αfroditi Orfanidou 1 , Hung-Chi Yang 3 , Kalliopi Zachou 5 , Chun-Jen Liu 3 , Anastasia Kourikou 4 , Niilis Gats Manolakopoulos 1 4 , George Dalekos 5 , Jia-Horng Kao 3 , Stephanos Hadziyannis 4 , George Papatheodoridis 1
隶属关系
隶属关系

    1
    消化内科，雅典国立和卡波迪斯特大学健康科学学院，雅典“莱科”总医院，希腊雅典。
    2
    伦敦大学学院肝脏和消化健康研究所，皇家自由校区，伦敦，英国。
    3
    台湾台北市国立台湾大学医院内科胃肠肝病科。
    4
    第二内科，雅典国立和卡波迪斯特大学健康科学学院，雅典“Hippokratio”总医院，希腊雅典。
    5
    希腊拉里萨拉里萨综合大学医院自身免疫性肝病国家专业中心内科医学部和研究实验室。

    PMID：34890120 DOI：10.1111/liv.15128

抽象的

背景和目的：关于核苷（酸）类似物（NA）停用对 HBeAg 阴性慢性乙型肝炎（CHBe-）肝细胞癌（HCC）风险影响的数据很少。因此，我们评估了与继续使用 NA 的非肝硬化 CHBe 患者相比，停药的患者的 HCC 风险是否增加。

方法：该队列研究包括 650 名无 HCC 病史的连续非肝硬化白种人或亚洲 CHBe 患者，他们在中位时间为 5 或 3 年后停止 NAs（病例，n=325；白种人：143，亚洲人：182）或分别接受 NA 治疗超过 5 年或 3 年（对照组，n=325；白种人：223，亚洲人：102）。应用倾向评分 (PS) 1:1 匹配来调整患者的来源、年龄和性别。

结果：在 44 个月的中位随访期间，7/325 例病例和 9/325 例对照或 7/245 PS 匹配病例和 7/245 PS 匹配对照发生 HCC，5 年累积 HCC 发生率为 5.1% 和分别为 4.9%（对数秩，P=0.836）。在白种人（3.0% 对 4.8%；对数秩，P=0.510）或亚洲血统（1.3% 对 2.2%；对数秩，P=0.873）的病例和对照之间观察到 5 年 HCC 风险没有差异。在病例和对照中，HCC 发生率与年龄和 PAGE-B 评分独立相关。仅就病例而言，停止 NA 后 HCC 的发展仅与治疗前血小板计数和 PAGE-B 评分相关，但与任何类型的复发或 HBsAg 消失无关。

结论：我们的研究结果表明，非肝硬化 CHBe 患者停止有效的长期 NA 治疗与 HCC 风险增加无关，后者不受 NA 后复发和/或 HBsAg 消失的影响。

关键词：停产；恩替卡韦；肝癌;核苷类似物；替诺福韦。

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StephenW

ssHepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicenter cohort study
Margarita Papatheodoridi  1   2 , Tung-Hung Su  3 , Emilia Hadziyannis  4 , Chun-Hsun Liao  3 , Αfroditi Orfanidou  1 , Hung-Chi Yang  3 , Kalliopi Zachou  5 , Chun-Jen Liu  3 , Anastasia Kourikou  4 , Nikolaos Gatselis  5 , Spilios Manolakopoulos  1   4 , George Dalekos  5 , Jia-Horng Kao  3 , Stephanos Hadziyannis  4 , George Papatheodoridis  1
Affiliations
Affiliations

    1
    Department of Gastroenterology, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Laiko", Athens, Greece.
    2
    University College of London, Institute of Liver and Digestive Health, Royal Free Campus, London, UK.
    3
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
    4
    2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece.
    5
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.

    PMID: 34890120 DOI: 10.1111/liv.15128

Abstract

Background & aims: Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs.

Methods: This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n=325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years, respectively (controls, n=325; Caucasians: 223, Asians: 102). Propensity-score (PS) 1:1 matching was applied to adjust for patients' origin, age and sex.

Results: During median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5-year cumulative HCC incidence of 5.1% and 4.9%, respectively (log-rank, P=0.836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P=0.510) or Asian origin (1.3% vs 2.2%; log-rank, P=0.873). In both cases and controls, HCC incidence was independently associated with age and PAGE-B score. In cases alone, HCC development after NA discontinuation was associated only with pretreatment platelet counts and PAGE-B score, but not with any type of relapse or HBsAg loss.

Conclusions: Our findings suggest that discontinuation of effective long-term NA therapy in non-cirrhotic CHBe- patients is not associated with increased HCC risk, which is not affected by post-NA relapses and/or HBsAg loss.

Keywords: discontinuation; entecavir; liver cancer; nucleoside analogue; tenofovir.

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