Abstract
Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers.
The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH).
NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor.
In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses.
Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.
Conclusions
Obesity has become a serious public health problem in the United States and elsewhere due to its effects on human health, resulting in metabolic and cardiovascular disorders and increasing cancer risk. Amongst all cancers, the one that is most strongly enhanced by obesity is HCC. Obesity enhances HCC development through lipid accumulation within hepatocytes, thereby leading to a chronic low-grade liver inflammation, involving various cytokines and adipokines.
Extensive research in this field has shed some light on some of the cytokines and adipokines that contribute to the onset of steatohepatitis and the initiation and promotion of HCC.
However, there are many questions, including the effect of hepatosteatosis on genetic instability within hepatocytes, the mechanisms that control the progression from hepatosteatosis to steatohepatitis and how chronic steatohepatitis leads to tumor initiation, that remain to be answered. While weight loss by bariatric surgery, diet or exercise have been shown to ameliorate obesity-induced metabolic syndromes, more effective therapeutic interventions are needed to prevent the development of HCC or halt its progression. The basic research reviewed above has revealed several new targets for therapeutic and preventive intervention, but advanced translational research has only begun.
Authors:
Beicheng Sun
Michael Karin
Source: Journal of Hepatology EASL
Published: November 24, 2011
Link: https://www.journal-of-hepatology.eu/article/S0168-8278(11)00804-X/fulltext
DOI:https://doi.org/10.1016/j.jhep.2011.09.020
