ABSTRACT
The prevalence of obesity and metabolic consequences, including non-alcoholic fatty liver disease (NAFLD) has become a global health problem. Obesity has an important impact on chronic liver disease even beyond NAFLD, as it accelerates the progression of alcohol liver disease. Conversely, even moderate alcohol use can affect NAFLD disease severity. Weight loss is the gold standard treatment but adherence to lifestyle changes is very low in the clinical setting. Bariatric surgery can improve metabolic components and cause long-term weight loss. Therefore, bariatric surgery could serve as an attractive treatment option for NAFLD patients. A pitfall is the use of alcohol after bariatric surgery. This short review integrates data about the influence of obesity and alcohol on liver function and the role of bariatric surgery.
Subject(s)
Bariatric Surgery , Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Humans , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/surgery , Obesity, Morbid/complications , Obesity, Morbid/surgery , Liver , Obesity/complications , Obesity/surgery , Weight LossABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and an increasing cause of liver cirrhosis and hepatocellular carcinoma. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a key pathophysiological mechanism contributing to NAFLD progression. Major triggers for angiogenesis in NAFLD include tissue hypoxia, structural and dynamic endothelial cell dysfunction, stellate cell activation and macrophage-mediated inflammation. In turn, angiogenesis drives inflammation and is closely linked to the progression of liver fibrosis and the development of liver cancer. In particular, the molecular crosstalk between pro-angiogenic endothelial cells and activated stellate cells can result in a positive feedback loop in which angiogenesis and fibrosis develop in parallel. In this review, we highlight the molecular mechanisms, drivers and consequences of angiogenesis in the progression of NAFLD to NASH, fibrosis and hepatocellular carcinoma. Evidence from animal and clinical studies suggests that mediators of angiogenesis and endothelial dysfunction are promising disease biomarkers, and that inhibiting angiogenesis may improve the course of NAFLD.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Neovascularization, Pathologic , Non-alcoholic Fatty Liver Disease , Animals , Disease Progression , Endothelial Cells , Humans , Liver , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease/pathologyABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, dyslipidemia and insulin resistance. NAFLD often presents as simple steatosis (NAFL) but can progress to non-alcoholic steatohepatitis (NASH) and fibrosis. Current non-invasive biomarkers are not tailored to identify significant (⩾F2) fibrosis, although recent guidelines recommend a stringent follow-up of this patient population. We and others have reported on the role of pathological angiogenesis in the pathogenesis of NAFLD, highlighting pro-angiogenic factors as potential diagnostic markers. OBJECTIVE: To investigate the applicability of angiogenic and endothelial dysfunction markers as non-invasive diagnostic tools for NASH or NASH-associated fibrosis in obese patients. METHODS: In a prospective cross-sectional study, male patients undergoing bariatric surgery (n=61) and control patients (n=35) were recruited. Serum protein levels and visceral adipose tissue gene expression of endothelial dysfunction and angiogenic markers were analyzed by multiplex bead-based assay and quantitative RT-PCR, respectively. For validation, we recruited a second cohort of patients undergoing bariatric surgery (n=40) and a cohort of NAFLD patients from our outpatient clinic (n=30). RESULTS: We identified serum vascular cell adhesion molecule-1 (VCAM-1) as an independent predictor for ⩾F2 fibrosis (median 14.0 vs 8.7 ng ml-1 in patients with and without significant fibrosis; P<0.0001) with an area under the receiver-operating characteristics (AUROC) curve of 0.80. The cutoff point of 13.2 ng ml-1 showed a sensitivity of 80% and specificity of 83%. In line with these results, VCAM-1 visceral adipose tissue gene expression was also elevated in patients with fibrosis (P=0.030). In the bariatric surgery and clinical validation cohorts, VCAM-1 displayed similar AUROCs of 0.89 and 0.85, respectively. CONCLUSIONS: VCAM-1 levels are able to accurately predict significant (⩾F2) fibrosis in NAFLD patients.
