Abstract
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The patatin-like phospholipase-3 (PNPLA3) I148M sequence variant is one of the strongest genetic determinants of NAFLD/NASH. PNPLA3 is an independent risk factor for HCC among patients with NASH. The obesity epidemic is closely associated with the rising prevalence and severity of NAFLD/NASH. Furthermore, metabolic syndrome exacerbates the course of NAFLD/NASH. These factors are able to induce apoptosis and activate immune and inflammatory pathways, resulting in the development of hepatic fibrosis and NASH, leading to progression toward HCC. Small intestinal bacterial overgrowth (SIBO), destruction of the intestinal mucosa barrier function and a high-fat diet all seem to exacerbate the development of hepatic fibrosis and NASH, leading to HCC in patients with NAFLD/NASH. Thus, the intestinal microbiota may play a role in the development of NAFLD/NASH. In this review, we describe recent advances in our knowledge of the molecular mechanisms contributing to the development of hepatic fibrosis and HCC in patients with NAFLD/NASH.
Highlights
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a leading cause of liver-related morbidity and mortality in the United States [1]
We focus on the molecular mechanisms shared by NAFLD, including NASH and hepatocellular carcinoma (HCC) development, and we discuss recent findings on the molecular mechanisms underlying NAFLD, NASH and HCC
Insulin resistance is a driver of the progression of NAFLD, and diabetes mellitus is highly predictive of the progression of simple steatosis to advanced liver fibrosis [20]
Summary
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a leading cause of liver-related morbidity and mortality in the United States [1]. NASH presents with increased hepatic fibrosis and progresses to end-stage liver disease [2]. Patients with NASH have a potential risk of developing hepatocellular carcinoma (HCC) [3]. Clinicians should be aware of the possibility of an occurrence of HCC in patients with NASH and the importance of prevention of NAFLD, including NASH, in adults as well as adolescents [4]. Steatohepatitis is a morphological pattern of liver injury that may be seen in both NAFLD and alcoholic liver disease [5]. The concept of NASH was first established in the context of pathology studies of the liver [5,6]. We focus on the molecular mechanisms shared by NAFLD, including NASH and HCC development, and we discuss recent findings on the molecular mechanisms underlying NAFLD, NASH and HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
