代谢功能障碍相关性脂肪性肝炎降低了慢性乙型肝炎患者的干扰素和巨噬细胞肝基因特征

IF 26.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Hepatology Pub Date : 2024-10-26 DOI:10.1016/j.jhep.2024.10.032
Zgjim Osmani, Willem Pieter Brouwer, Dwin G.B. Grashof, Youkyung Lim, Michael Doukas, Harry L.A. Janssen, Harmen J.G. van de Werken, Andre Boonstra
{"title":"代谢功能障碍相关性脂肪性肝炎降低了慢性乙型肝炎患者的干扰素和巨噬细胞肝基因特征","authors":"Zgjim Osmani, Willem Pieter Brouwer, Dwin G.B. Grashof, Youkyung Lim, Michael Doukas, Harry L.A. Janssen, Harmen J.G. van de Werken, Andre Boonstra","doi":"10.1016/j.jhep.2024.10.032","DOIUrl":null,"url":null,"abstract":"<h3>Background &amp; Aims</h3>Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection.<h3>Methods</h3>Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B.<h3>Results</h3>There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., <em>IFIT2</em>, <em>IFI27</em>, <em>IFITM1</em>, <em>IFI6</em>), and macrophage gene signatures (e.g., <em>MARCO</em>, <em>CD163</em>, <em>CD5L</em>, <em>CD63</em>), when compared to patients with ENEG alone.<h3>Conclusions</h3>Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.<h3>Impact and implications</h3>In recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chronic hepatitis B.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":26.8000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metabolic dysfunction-associated steatohepatitis reduces interferon and macrophage liver gene signatures in patients with chronic hepatitis B\",\"authors\":\"Zgjim Osmani, Willem Pieter Brouwer, Dwin G.B. Grashof, Youkyung Lim, Michael Doukas, Harry L.A. Janssen, Harmen J.G. van de Werken, Andre Boonstra\",\"doi\":\"10.1016/j.jhep.2024.10.032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background &amp; Aims</h3>Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection.<h3>Methods</h3>Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B.<h3>Results</h3>There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., <em>IFIT2</em>, <em>IFI27</em>, <em>IFITM1</em>, <em>IFI6</em>), and macrophage gene signatures (e.g., <em>MARCO</em>, <em>CD163</em>, <em>CD5L</em>, <em>CD63</em>), when compared to patients with ENEG alone.<h3>Conclusions</h3>Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.<h3>Impact and implications</h3>In recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chronic hepatitis B.\",\"PeriodicalId\":15888,\"journal\":{\"name\":\"Journal of Hepatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":26.8000,\"publicationDate\":\"2024-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jhep.2024.10.032\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jhep.2024.10.032","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景& 目的 已有研究表明,与单纯慢性 HBV 患者相比,合并代谢功能障碍相关性脂肪性肝炎(MASH)的慢性 HBV 患者纤维化发展更快,肝病更严重。然而,我们对其潜在机制的了解还很有限。在此,我们研究了 MASH 并发症如何影响慢性 HBV 感染患者肝脏中的免疫活性。方法对仅有 MASH(10 例)、仅有 HBeAg 阴性慢性 HBV(ENEG;11 例)、合并 MASH/ENEG (9 例)和健康对照组(9 例)患者的肝活检组织进行大肠 RNA 测序。我们选择了无纤维化或纤维化程度极低(≤F2)的活检样本,以避免纤维化的混杂影响。我们比较了MASH/ENEG患者和单纯ENEG患者的全转录组数据,以确定MASH并发症对慢性乙型肝炎的影响。结果与健康对照组相比,单纯ENEG患者和单纯MASH患者的肝脏基因表达谱高度重叠,表明这些不同病症的肝脏功能障碍和免疫活动机制基本相同。在 ENEG 患者中,MASH 并发症显著降低了干扰素通路活性(NES=2.03,p.adj=0.0251)、ISGs(如 IFIT2、IFI27、IFITM1、IFI6)和巨噬细胞基因特征(如 MARCO、CD163、CD164、CD165、CD166、CD167、CD168)的表达、结论肝脏转录组学分析表明,MASH 对 ENEG 患者肝脏中 ISGs 的表达有负面影响,这可能会影响抗病毒免疫途径、病毒复制和炎症反应,导致慢性乙型肝炎患者发生晚期纤维化的风险增加。影响和意义近几十年来,肥胖和相关健康问题已达到流行病的程度,在发达国家,高达 30% 的成年人患有脂肪肝,慢性乙型肝炎患者中也出现了这种趋势。鉴于脂肪性肝病的发病率很高而且还在不断上升,而且慢性乙型肝炎患者中也经常出现脂肪性肝病,因此了解代谢功能障碍相关性脂肪性肝炎(MASH)等疾病如何影响肝脏的免疫反应至关重要。这项研究提供了关于代谢功能障碍相关性脂肪性肝炎(MASH)对慢性乙型肝炎患者肝脏中 HBV 抗病毒免疫活性的影响的独特见解。我们的研究对指导未来针对 MASH 和慢性乙型肝炎患者制定治疗策略的研究具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Metabolic dysfunction-associated steatohepatitis reduces interferon and macrophage liver gene signatures in patients with chronic hepatitis B

Background & Aims

Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection.

Methods

Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B.

Results

There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., IFIT2, IFI27, IFITM1, IFI6), and macrophage gene signatures (e.g., MARCO, CD163, CD5L, CD63), when compared to patients with ENEG alone.

Conclusions

Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.

Impact and implications

In recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chronic hepatitis B.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Hepatology
Journal of Hepatology 医学-胃肠肝病学
CiteScore
46.10
自引率
4.30%
发文量
2325
审稿时长
30 days
期刊介绍: The Journal of Hepatology is the official publication of the European Association for the Study of the Liver (EASL). It is dedicated to presenting clinical and basic research in the field of hepatology through original papers, reviews, case reports, and letters to the Editor. The Journal is published in English and may consider supplements that pass an editorial review.
期刊最新文献
Unlock AI-Safe-C score's potential at all levels: Improve methods and overcome barriers Non-invasive algorithms could outperform HVPG in selecting candidates for non-selective beta-blockers in cirrhosis Adipose triglyceride lipase as a target for treatment of metabolic dysfunction-associated steatohepatitis: the role of hepatic and intestinal PPARα Surrender to evidence: the futility of plasma exchange for severe liver disease and liver failure Activating hepatobiliary water channels for gallstone prevention in complicated gallstone disease
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1