Abstract

Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Highlights

  • With advancements in medicine, many diseases can be controlled, but cancer continues to pose many challenges

  • Several studies indicated that BCAAs could inhibit triglyceride (TG) deposition in hepatocytes, reduce endoplasmic reticulum (ER) stress, and enhance gut barrier function by improving immune response, some inconsistencies in the results indicated that BCAAs caused hepatic damage, associated with abnormal lipolysis, in mice on high-fat diets (HFDs) [71,72,73]

  • The current non-alcoholic fatty liver disease (NAFLD) therapeutic strategies based on the gut microbiota and gut–liver axis mainly include prebiotic, probiotic, and fecal microbial transplantation (FMT) application

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Summary

Introduction

Many diseases can be controlled, but cancer continues to pose many challenges. Chronic viral hepatitis caused by hepatitis B and C viruses (HBV and HCV, respectively) is a major risk factor of HCC [3]. The incidence of viral hepatitis-related liver cirrhosis and HCC is expected to decline. Other important causative risk factors of HCC include non-alcoholic fatty liver disease (NAFLD), obesity, diabetes, and alcoholism [5]. NAFLD is the second most common cause of end-stage liver disease or liver cancer, which requires liver transplantation, in the United States [6,7,8]. NAFLD progression can be divided into four pathological stages, including non-alcoholic simple fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), hepatic cirrhosis, and HCC [10] (Figure 1). Spolemmeenptoedtefnotriaful tduiraegcnlionsitciacl aanpdplitchaetrioanpse,uwtiecrehiingchlulidgehdts. , which could be implemented for future clinical applications, were included

From NAFL to NASH
NASH and Leaky Gut
NASH and Gut Microbiota-Derived Metabolites
From NASH to HCC
Findings
Conclusions

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