核苷（酸）类似物对慢性乙型肝炎患者在干扰素-λ3诱导下降低乙肝表面抗原的影响。

Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon-lambda 3 induction in chronic hepatitis B patients.

作者信息

Umemura Machiko, Ogawa Koji, Morikawa Kenichi, Kubo Akinori, Tokuchi Yoshimasa, Yamada Ren, Kitagataya Takashi, Shigesawa Taku, Shimazaki Tomoe, Kimura Megumi, Suzuki Kazuharu, Nakamura Akihisa, Ohara Masatsugu, Kawagishi Naoki, Izumi Takaaki, Nakai Masato, Sho Takuya, Suda Goki, Natsuizaka Mitsuteru, Ono Kota, Murata Kazumoto, Sugiyama Masaya, Mizokami Masashi, Sakamoto Naoya

机构信息

Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.

Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan.

出版信息

Hepatol Res. 2022 Jul;52(7):586-596. doi: 10.1111/hepr.13768. Epub 2022 Apr 12.

DOI:10.1111/hepr.13768

PMID:35352445

Abstract

BACKGROUND & AIMS: Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-λ3 levels in chronic hepatitis B (CHB) patients.

METHODS

A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post-therapy.

RESULTS

The change (mean ± standard deviation) in serum HBsAg levels from baseline to year five was -0.38 ± 0.46 and -0.84 ± 0.64 log IU/ml in ETV and ADV/TDF groups, respectively (p = 0.0004). Higher serum IFN-λ3 levels were observed in ADV/TDF group compared with ETV group during treatment (p < 0.001). Serum IFN-λ3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = -0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/TDF) treatment has associated factors with -0.3 log HBsAg decline at 1 year, -0.5 log HBsAg decline at 3 years, and -0.8 log HBsAg decline at 5 years after NAs treatment on multivariate analysis.

CONCLUSIONS

Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-λ3 induction.

摘要

背景与目的

核苷（酸）类似物（NAs）对乙型肝炎表面抗原（HBsAg）降低及干扰素-λ3（IFN-λ3）诱导的益处仍不明确。本研究旨在探讨NAs对慢性乙型肝炎（CHB）患者HBsAg降低的影响以及与血清IFN-λ3水平的相关性。

方法

本研究共纳入91例有临床症状的CHB患者（慢性肝炎57例，肝硬化34例），其中51例接受核苷类似物水合恩替卡韦（ETV）治疗，40例接受核苷酸类似物阿德福韦酯（ADV）或替诺福韦酯（TDF）治疗。在治疗开始前以及治疗后1年、3年和5年，检测接受ETV和ADV/TDF治疗患者的血清IFN-λ3水平。

结果

ETV组和ADV/TDF组血清HBsAg水平从基线到第5年的变化（均值±标准差）分别为-0.38±0.46和-0.84±0.64 log IU/ml（p = 0.0004）。治疗期间，ADV/TDF组血清IFN-λ3水平高于ETV组（p < 0.001）。在第48周时，ADV/TDF组血清IFN-λ3水平与HBsAg降低呈负相关（r = -0.386，p = 0.038）。多因素分析显示，核苷酸类似物（ADV/TDF）治疗在治疗1年、3年和5年后，与HBsAg下降0.3 log、0.5 log和0.8 log相关。