Etiology-Dependent Microbiome Differences in Hepatocellular Carcinoma Development

Abstract

Chronic liver disease is characterised by persistent inflammation, tissue damage, and regeneration, which leads to steatosis, fibrosis, and, lastly, cirrhosis and hepatocellular carcinoma (HCC). HCC, the most prevalent form of primary liver cancer, is one of the leading causes of cancer-related mortality worldwide. The gut microbiota plays a fundamental role in human physiology, and disturbances in its critical balance are widely recognised as contributors to various pathological conditions, including chronic liver diseases, both infectious and non-infectious in nature. Growing interest in microbiota research has recently shifted the focus towards the study of intratumoural microbiota, referred to as the "oncobiome", which can significantly impact the development and progression of HCC. In this review, we discuss existing research and provide an overview of the microbiota influence on viral hepatitis, particularly in shaping the progression of liver disease caused by the hepatitis B and hepatitis C viruses. We also explore microbial dysbiosis and its contribution to the silent and dangerous progression of non-alcoholic fatty liver disease. Additionally, we address the impact of alcohol on the liver and its interaction with the microbiota, tracing the pathway from inflammation to cirrhosis and cancer. The review emphasises the most common etiologies of hepatocellular carcinoma.

Keywords: cirrhosis; fibrosis; gut microbiota; hepatocellular carcinoma; oncobiome; steatosis.

Figure 1

The role of microbiota in HCC. Impact of viral hepatitis, NAFLD, and ALD on microbiota, and subsequent consequences, which lead to chronic liver disease, with HCC development as a final stage. ALD—alcoholic liver disease; GM—gut microbiota; HCC—hepatocellular carcinoma; NAFLD—nonalcoholic fatty liver disease; TLR—Toll-like receptor.