在严格定义的未经治疗的慢性乙型肝炎免疫阶段中，HCC风险

StephenW

Negligible HCC risk during stringently defined untreated immune-tolerant phase of chronic hepatitis B
Hye Won Lee  1 , Young Eun Chon  2 , Beom Kyung Kim  1 , Terry Cheuk-Fung Yip  3 , Yee-Kit Tse  3 , Grace Lai-Hung Wong  3 , Vincent Wai-Sun Wong  3 , Henry Lik-Yuen Chan  4 , Sang Hoon Ahn  5
Affiliations
Affiliations

    1
    Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
    2
    Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea.
    3
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong; Hong Kong SAR, China.
    4
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong; Hong Kong SAR, China. Electronic address: [email protected].
    5
    Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea. Electronic address: [email protected].

    PMID: 33288393 DOI: 10.1016/j.ejim.2020.10.022

Abstract

Background & aims: Whether chronic hepatitis B (CHB) patients during immune-tolerant (IT) phase are at low risk of hepatocellular carcinoma (HCC) is still controversial. We performed a multicenter study to determine their long-term prognosis.

Methods: Untreated IT group included patients < 40 years of age, with persistently hepatitis B e antigen [HBeAg] positivity, serum HBV-DNA>6 log10IU/mL, and ALT level < 40 U/L, using age and HBV-DNA criteria by the American Association for the Study of Liver Diseases (AASLD) guideline. Cumulative HCC risk of untreated IT group (n=194) was compared to HBeAg-positive patients undergoing antiviral therapy according to the practice and reimbursement guidelines (treated HBeAg[+] group, n=454). Patients with history of cirrhosis or HCC at baseline were excluded.

Results: During follow-up (median 62.1 months), HCC did not develop in any patient among untreated IT group, whereas the cumulative probability of HCC at 3, 5, and 9 years in the treated HBeAg(+) group was 0.5%, 0.7%, and 1.3%, respectively (p=0.203). Ninety-seven patients among untreated IT group entered immune-active phase, of whom 86 (88.7%) started antiviral treatment. A high normal ALT level (20-39 U/L) was associated with an increased risk of a phase change, compared to ALT < 20 U/L. After censoring at the time of phase change, the cumulative HCC risk was also not significantly different between two groups (p=0.258).

Conclusions: No actual HCC risk during untreated IT phase defined by age and HBV-DNA criteria of the AASLD guideline exists, supporting their diagnostic validity from the perspective of long-term prognosis. Further validation studies are required.

Keywords: Antiviral therapy; Hepatitis B e antigen; Hepatitis B virus; Hepatocellular carcinoma; Immune-tolerant.

Copyright © 2020. Published by Elsevier B.V.

StephenW

在严格定义的未经治疗的慢性乙型肝炎免疫阶段中，HCC风险可忽略不计
李慧媛1，英恩俊2，范京金1，叶德凤3，谢绮洁3，黄丽红3，黄文顺3，陈利源4，桑勋安5
隶属关系
隶属关系

    1个
    延世大学医学院内科，韩国首尔；延世大学医学院胃肠病研究所，韩国首尔；大韩民国首尔遣散医院延世肝脏中心。
    2
    大韩民国城南大学茶本堂医学中心内科。
    3
    香港中文大学消化病研究所，香港特别行政区；香港中文大学，香港特别行政区医学与治疗学系；香港中文大学消化系统疾病国家重点实验室；中国香港特别行政区。
    4
    香港中文大学消化病研究所，香港特别行政区；香港中文大学，香港特别行政区医学与治疗学系；香港中文大学消化系统疾病国家重点实验室；中国香港特别行政区。电子地址：[email protected]。
    5
    延世大学医学院内科，韩国首尔；延世大学医学院胃肠病研究所，韩国首尔；大韩民国首尔遣散医院延世肝脏中心。电子地址：[email protected]。

    PMID：33288393 DOI：10.1016 / j.ejim.2020.10.022

抽象

背景与目的：免疫耐受（IT）阶段的慢性乙型肝炎（CHB）患者是否处于肝细胞癌（HCC）的低风险仍存在争议。我们进行了一项多中心研究以确定他们的长期预后。

方法：未经治疗的IT组包括年龄<40岁，持续乙型肝炎e抗原[HBeAg]阳性，血清HBV-DNA> 6 log10IU / mL，ALT水平<40 U / L（按年龄和HBV-DNA标准）的患者由美国肝病研究协会（AASLD）指南制定。根据实践和报销指南，将未经治疗的IT组（n = 194）与接受抗病毒治疗的HBeAg阳性患者的累积HCC风险进行比较（治疗的HBeAg [+]组，n = 454）。基线时有肝硬化或HCC病史的患者被排除在外。

结果：在随访期间（中位62.1个月），未经治疗的IT组中没有任何患者发生HCC，而经过治疗的HBeAg（+）组在3、5和9岁时的HCC累积概率为0.5％，分别为0.7％和1.3％（p = 0.203）。未经治疗的IT组中有97名患者进入了免疫活性期，其中86名患者（88.7％）开始了抗病毒治疗。与ALT <20 U / L相比，正常ALT高水平（20-39 U / L）与相变风险增加有关。在进行相变时进行检查后，两组的累积HCC风险也没有显着差异（p = 0.258）。

结论：没有根据年龄和AASLD指南的HBV-DNA标准定义的未治疗IT阶段的实际HCC风险，从长期预后的角度支持其诊断有效性。需要进一步的验证研究。

关键字：抗病毒治疗；乙型肝炎e抗原；乙型肝炎病毒;肝细胞癌；免疫耐受。

版权所有©2020。由Elsevier B.V.发布。