Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure.

Xiaoyu Fu,Da Cheng,Shifang Peng,Lei Fu,Yi Ouyang,Ying Li,Ronghua Li,Naohiko Masaki

doi:10.1155/2021/5387856

Abstract

People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF.

Highlights

Hepatitis B virus (HBV) is a global epidemic disease
If the transcripts were not overlapped with the protein-coding genes but overlapped with the annotated Long noncoding RNAs (lncRNAs), the transcripts were considered as known lncRNAs
Our study provides a novel compendium of lncRNAs expressed in the progression of chronic HBV infection to acute-on-chronic liver failure (ACLF)

Summary

Introduction

Hepatitis B virus (HBV) is a global epidemic disease. According to a report from the World Health Organization, approximately 2 billion people worldwide are infected with HBV, with 240 million of them presenting chronic HBV infections. In China, 93 million people are infected with chronic HBV every year, and approximately 30% patients present spontaneous hepatitis acute exacerbation, with some patients progressing to acute-on-chronic liver failure (ACLF) with a high fatality rate. ACLF can lead to severe clinical syndromes such as jaundice, blood coagulation dysfunction, hepatic encephalopathy, and ascites [2, 3]. Experts have considered ACLF as a new type of liver disease with short-term mortality rate (generally 28 days) and dysfunctional systematic inflammatory response. It is difficult to distinguish the initial clinical symptoms between ACLF and severe chronic hepatitis. The short-term case fatality rate reaches up to >50% when the disease progresses to liver failure [4]. It is important to prevent the occurrence of liver failure during the early clinical period

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