Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC

Int J Mol Sci. 2021 Apr 26;22(9):4495. doi: 10.3390/ijms22094495.

Abstract

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type 2 diabetes contributes to biological processes driving the severity of NAFLD, the primary cause for development of chronic liver diseases. In the last 20 years, the rate of non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs for treatment of NAFLD and NASH, a class of thiazolidinediones (TZDs) drugs for the treatment of type 2 diabetes is sometimes used to improve liver failure despite the risk of side effects. Therefore, diagnosis, prevention, and treatment of the development and progression of NAFLD and NASH are important issues. In this review, we will discuss the pathogenesis of NAFLD/NASH and NAFLD/NASH-derived HCC and the current promising pharmacological therapies of NAFLD/NASH. Further, we will provide insights into "adipose-derived adipokines" and "liver-derived hepatokines" as diagnostic and therapeutic targets from NAFLD to HCC.

Keywords: adipokines; hepatocellular carcinoma (HCC); hepatokines; non-alcholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); obesity; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Adipokines / metabolism
  • Carcinoma, Hepatocellular / physiopathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism
  • Disease Progression
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis / physiopathology
  • Liver Failure
  • Liver Neoplasms / physiopathology
  • Metabolic Syndrome / physiopathology
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Obesity / complications*
  • Obesity / metabolism

Substances

  • Adipokines