ABSTRACT
NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotoxicity, and bile acid (BA) toxicity, have been reported to be associated with NASH progression. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, which is caused by the ectopic accumulation of triglyceride-derived toxic metabolites and the subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. Adipose tissue (AT), especially visceral AT, comprises multiple cell populations that produce adipokines and insulin-like growth factor, plus macrophages and other immune cells that stimulate the development of lipotoxic liver disease. These biomolecules have been recently linked with many digestive diseases and gastrointestinal malignancies such as hepatocellular carcinoma. This made us question what role lipotoxicity has in the natural history of liver fibrosis. Therefore, this review focuses on the close relationship between AT and NASH. A good comprehension of the pathways that are related to dysregulated AT, metabolic dysfunction, and hepatic lipotoxicity will result in the development of prevention strategies and promising therapeutics for patients with NASH.
Subject(s)
Adipose Tissue/pathology , Liver Cirrhosis/pathology , Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , Adipokines/metabolism , Adipose Tissue/metabolism , Disease Progression , Fatty Acids/metabolism , Humans , Insulin Resistance , Liver/metabolism , Liver Cirrhosis/metabolism , Models, Biological , Non-alcoholic Fatty Liver Disease/metabolismSubject(s)
Non-alcoholic Fatty Liver Disease , Adult , Hispanic or Latino , Humans , Risk Factors , United States , White PeopleABSTRACT
AIM: To investigate the main current etiologies of cirrhosis in Mexico. METHODS: We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period (January 2012-December 2017). RESULTS: A total of 1210 patients were included. The mean age was 62.5 years (SD = 12.1), and the percentages of men and women were similar (52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus (HCV) (36.2%), alcoholic liver disease (ALD) (31.2%), and nonalcoholic steatohepatitis (23.2%), and the least frequent were hepatitis B virus (1.1%), autoimmune disorders (7.3%), and other conditions (1.0%). CONCLUSION: HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease (NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.