Gut Microbiota Dysbiosis in Patients With Hepatitis B Virus–Induced Chronic Liver Disease Covering Chronic Hepatitis, Liver Cirrhosis and Hepatocellular Carcinoma

Yongbin Zeng; Shanjian Chen; Ya Fu; Wennan Wu; Tianbin Chen; Jing Chen; Bin Yang; Qishui Ou


J Viral Hepat. 2020;27(2):143-155. 

In This Article

Abstract and Introduction


The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus–induced chronic liver disease (HBVCLD) is limited. In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus–induced chronic liver disease patients and healthy individuals. Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals. The 16S rDNA gene amplification products were sequenced. Bioinformatic analysis including alpha diversity and PICRUSt was performed. A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected. The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially. The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls. Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism–related genes in HBVCLD than in healthy individuals. Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes. Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.


Approximately 250 million people are chronically infected with hepatitis B virus (HBV) worldwide.[1] Chronic hepatitis B (CHB) patients are at a greater risk of developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC), resulting in nearly one million deaths annually.[1,2] Therefore, it is necessary to monitor disease progression in patients chronically infected with HBV.

The aetiology of hepatitis B virus–induced chronic liver disease (HBVCLD) is complex and involves viral (such as genotype, quasispecies, etc), genetic (such as human single-nucleotide polymorphism) and environmental factors;[2,3] and recently, one of the environmental exposures, gut microbiota, has attracted considerable attention as a risk factor for the progression of liver disease.[4] The gut microbiota, reported as a 'forgotten organ', carrying more than 100 trillion microorganisms and containing 100–150-fold more genes than the human genome, plays important roles in many aspects of the host pathophysiology of many intestinal and extra-intestinal diseases, including metabolism, immunity and neurophysiology as well as chronic liver diseases.[4,5]

It is well known that the communication between gut and liver is via tight bidirectional links through the biliary tract, the hepatic portal vein and the bile secretion systems. In the liver, the hepatocytes secrete bile and many bioactive mediators into the biliary tract and the systemic circulation.[6,7] While in the intestine, the intestinal blood carries nutrients including endogenous (bile acids and amino acids) as well as exogenous (from diet and environmental exposure) substrates from the gut to activate liver functions to promote the effective hepatic processing of nutrients through the portal vein.[7] Consequently, gut homeostasis is essential for health. Whereas in some situations, an alteration of the gut microbial composition, usually termed dysbiosis, can cause the translocation of microbial-derived metabolic products such as lipopolysaccharides (LPS), endogenous ethanol and other noxious mediators via the portal vein, which may induce liver damage.[4,8]

Over the past years, accumulating evidence had suggested that the gut-liver axis played critical parts in the pathogenesis of liver diseases including hepatitis and nonalcoholic steatohepatitis (NASH).[4] A more recent study has demonstrated the effect of hepatitis C virus (HCV) infection on gut microbiota and the relationship between alteration of gut microbiota and chronic hepatitis C (CHC) progression.[9] However, less attention was focused on the interactions between the different clinical stages of HBV-infected patients and human gut microbiota. Consequently, in this study, to investigate the profile of gut microbiota in different clinical stages of chronic HBV infection and the presence of core and unique microbiota, we used high-throughput 16S rDNA gene sequencing to characterize gut microbiota in HBVCLD patients including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.