Abstract
Simple SummaryHepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related deaths worldwide; its incidence and mortality rate continue to increase. HCC has a poor prognosis and the curative options are very limited. The liver is closely connected (anatomically and functionally) to the gastrointestinal tract, which represents the largest reservoir of microbes in our body. Increasing evidence implicates communication between the liver and the intestine (and its microbiome) in the progression of chronic liver disease to liver cancer. In this review, we summarise current knowledge on the role of the gut–liver axis in contributing to the progression of HCC, with a focus on the impact of the intestinal microbiome in this process. We also review the potential of therapeutic strategies based on modulation of the microbiome for the prevention of HCC progression.Hepatocellular carcinoma (HCC) is the most common malignancy occuring in the context of chronic liver disease and is one of the main causes of cancer-derived death worldwide. The lack of effective treatments, together with the poor prognosis, underlines the urge to develop novel and multidisciplinary therapeutics. An increasing body of evidence shows that HCC associates with changes in intestinal microbiota abundance and composition as well as with impaired barrier function, leading to the release of bacteria and their metabolites to the liver. These factors trigger a cascade of inflammatory responses contributing to liver cirrhosis and constituting an ideal environment for the progression of HCC. Interestingly, the use of bacteriotherapy in human and preclinical studies of chronic liver disease and HCC has been shown to successfully modify the microbiota composition, reducing overall inflammation and fibrosis. In this review, we explore the existing knowledge on the characterisation of the intestinal microbial composition in humans and experimental murine chronic liver disease and HCC, as well as the use of antibiotics and bacteriotherapy as therapeutic options.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related deaths worldwide [1,2]
We summarise the contribution of the gut–liver axis to the progression from chronic liver disease into cirrhosis/HCC
Associations between particular microbiome compositions and the development of HCC are well supported in numerous studies of patients with HCC arising from different aetiologies, and we describe these in the sections below, with particular reference to alcoholic liver disease (ALD), nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and viral hepatitis
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related deaths worldwide [1,2]. HCC is the leading cause of mortality in cirrhotic patients. Due to an increase in the obesity-associated metabolic syndrome of epidemic proportions, NAFLD is becoming a leading cause of HCC in western countries, in elder patients with comorbidities. The precise mechanisms underpinning the progression from chronic (inflammatory) liver disease to cirrhosis/HCC remain largely undefined, though it is increasingly recognised that the gut–microbiome–liver axis plays an important role. We summarise the contribution of the gut–liver axis to the progression from chronic liver disease into cirrhosis/HCC. We focus on the role of the intestinal microbiome, in particular how the microbiome changes during the progression of chronic liver disease to HCC and the potential therapeutic effects of treatment strategies that target the microbiome
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