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Characterization of the Circulating Microbiome in Acute-on-Chronic Liver Failure Associated with Hepatitis B

39 Pages Posted: 7 Dec 2018

See all articles by Wei Wu

Wei Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Ruihong Zhao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Ding Shi

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Shanshan Sun

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Haotang Ren

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Hong Zhao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Yi Zhang

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Linfeng Jin

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Jifang Sheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Yu Shi

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

More...

Abstract

Aims: Patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF) may have an increased circulating microbial burden. This study aimed to assess circulating microbial load and composition and to explore the association between the circulating microbiome and both systemic inflammation and clinical outcome in HB-ACLF.  

Methods: Plasma from 49 HB-ACLF patients, 15 healthy controls (HCs) and 18 patients with compensated liver cirrhosis (C-LC) was analyzed for chemokines/cytokines and bacterial DNA and further analysed by 16S rDNA pyrosequencing. Linear discriminant analysis effect size (LEfSe) and inferred metagenomics analyses were performed.  

Results: The circulating bacterial DNA was significantly increased in HB-ACLF patients compared to that in the control groups. The overall microbial diversity was significantly decreased in HB-ACLF patients. HB-ACLF patients were enriched with Moraxellaceae, Sulfurovum, Comamonas, and Burkholderiaceae but were depleted in Actinobacteria, Deinococcus-Thermus, Alphaproteobacteria, Xanthomonadaceae and Enterobacteriaceae compared to controls. Networkanalysis revealed a direct positive correlation between Burkholderiaceae and chemokine IP-10 in HB-ACLF patients. The relative abundance of Prevotellaceae independently predicted 28-day mortality. Inferred functional metagenomics predicted an enrichment of bacteria with genes related to methane, alanine, aspartate, glutamate, pyrimidine, purine and energy metabolism.  

Conclusions: HB-ACLF patients display increased circulating microbial burden, altered microbiome composition and a shift in microbiome functionality. The dysbiosis in circulating microbiota is associated with systemic inflammation (SI) and clinical outcome in HB-ACLF.  

Funding Statement: This research was funded by [National Natural Science Foundation of China] grant numbers [81870425, 81500464, 81671949 and 81670567].  

Declaration of Interests: The authors declare that they have no conflict of interest.

Ethics Approval Statement: This study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of each participating hospital.

Keywords: ACLF; HBV; circulating microbial burden; circulating Microbiome; inferred functional metagenomics

Suggested Citation

Wu, Wei and Zhao, Ruihong and Shi, Ding and Sun, Shanshan and Ren, Haotang and Zhao, Hong and Zhang, Yi and Jin, Linfeng and Sheng, Jifang and Shi, Yu, Characterization of the Circulating Microbiome in Acute-on-Chronic Liver Failure Associated with Hepatitis B (January 12, 2018). Available at SSRN: https://ssrn.com/abstract=3296638

Wei Wu (Contact Author)

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Ruihong Zhao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Ding Shi

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Shanshan Sun

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Haotang Ren

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Hong Zhao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yi Zhang

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Linfeng Jin

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Jifang Sheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yu Shi

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

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