Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies?

Abstract

Hepatocellular cancer (HCC) is a cancer with an overall poor prognosis and an alarming globally rising incidence. While viral etiology of chronic liver disease and HCC is down-trending, alcohol and excess calorie intake have emerged as major culprits. Alcohol related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) share similar pathogenetic mechanism of hepatic injury and in promoting development of HCC; yet some genetic and epigenetic features are distinct and may promise clinical utility. Population based intervention are urgently needed to reduce alcohol use and improve metabolic factors such as obesity and diabetes. The goal is to identify at-risk patients, to link these patients to care and to provide effective management of chronic liver disease and HCC. This review focuses on the epidemiology, pathophysiology including genetic and epigenetic altercation as well as clinical aspects of ALD and NAFLD associated HCC.

Keywords: Alcoholic liver disease (ALD); hepatocellular cancer (HCC); non-alcoholic fatty liver disease (NAFLD).

Figure 1

Alcohol, diet, obesity, and genetic factors—all affect gut microbiota leading to dysbiosis with intestinal bacterial overgrowth, increased intestinal permeability with subsequent bacterial translocation and endotoxemia stimulating development of HCC. Figure was created and adapted from Gupta et al. 2019 (34). HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus; HSC, hepatic stellate cell; ROS, reactive oxygen species; TLR, toll-like receptor; IR, insulin resistance; LPS, lipopolysaccharide; TNF, tumor necrosis factor; SCFA, short-chain fatty acid; DAMP, damage-associated molecular patterns; PAMPs, pathogen-associated molecular patterns; TMA, trimethylamine.