The Role of Gut Microbiota in Hepatitis B Disease Progression and Treatment

Bryan Chen; Harry Huang; Calvin Q. Pan


J Viral Hepat. 2022;29(2):94-106. 

In This Article

Abstract and Introduction


Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the 'Gut-Liver Axis', where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.


It is estimated in 2018 that ~292 million individuals are chronically infected with hepatitis B virus (HBV) worldwide,[1] with nearly 887,000 annual deaths due to complications from chronic hepatitis B (CHB) infection like decompensated cirrhosis and hepatocellular carcinoma.[2] Although the natural history of CHB has been extensively studied,[3–5] the pathophysiology of HBV disease progression has not been fully explored. Current evidences suggest that HBV viraemia, HBV mutations and host immune activation heavily contribute to liver injury and disease progression.[6–8] Further development of therapeutic interventions have included direct acting antiviral therapy and/or immune moderators, with the goals of targeting risk modification (viral reduction), reducing hepatic inflammation and reversing liver fibrosis.[9–11]

The term 'Gut-Liver Axis' describes the uniquely intertwined relationship between the gut and liver organs. The link is bidirectional: the liver secretes bile into the intestines by the bile duct, while nearly all the blood carrying vital nutrients and other metabolites from the intestines are filtered through the liver via the hepatic portal vein before joining systemic circulation.[12] Normally, the gut hosts a myriad of microflora that play complex immunological and nutritional roles in both the gastrointestinal tract and the liver.[13,14] Abnormalities in either organs, such as liver disease and gut dysbiosis, are thus often correlated through interactions of dietary, genetic and environmentally-derived signals.[15–17]

Currently, therapeutic interventions, including peg-interferon and oral antiviral treatment, can only suppress HBV DNA replication or reduce complications of cirrhosis and/or hepatocellular carcinoma, but cannot cure CHB.[1,18,19] Therefore, further development of new treatment methods are critical for the global eradication of HBV. A growing body of literature suggests a connection between gut microbiota dysbiosis and disease progression in CHB patients.[20–27] Additionally, emerging data reveals that directed treatment of dysbiosis may have potential therapeutic value in liver disease and CHB management.[28–30] Therefore, it is necessary to clarify our understanding of the pathophysiology of gut microbiota, understand their relationship with liver injury in CHB, identify the data gap, and wholly assess the latest microbiota-targeted therapies in CHB patients. With these goals, we thus compose a network data review. Future research directions are also discussed.