Nonalcoholic Fatty Liver Disease: Current Issues and Novel Treatment Approaches

Abstract

Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world. It is commonly associated with insulin resistance, obesity, dyslipidaemia, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is characterized by steatosis with necroinflammation and eventual fibrosis, which can lead to end-stage liver disease and hepatocellular carcinoma. Its pathogenesis is complex, and involves a state of 'lipotoxicity' in which insulin resistance, with increased free fatty acid release from adipose tissue to the liver, play a key role in the onset of a 'lipotoxic liver disease' and its progression to NASH. The diagnosis of NASH is challenging, as most affected patients are symptom free and the role of routine screening is not clearly established. A complete medical history is important to rule out other causes of fatty liver disease (alcohol abuse, medications, other). Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for a definitive diagnosis. However, there is an active search for plasma biomarkers and imaging techniques that may non-invasively aid in the diagnosis. The treatment of NASH requires a multifaceted approach. The goal is to reverse obesity-associated lipotoxicity and insulin resistance via lifestyle intervention. Although there is no pharmacological agent approved for the treatment of NAFLD, vitamin E (in patients without T2DM) and the thiazolidinedione pioglitazone (in patients with and without T2DM) have shown the most consistent results in randomized controlled trials. This review concentrates on our current understanding of the disease, with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH.

Toxicogenomic module associations with pathogenesis: a network-based approach to understanding drug toxicity

“…71 However, establishing the relevance of insights obtained from transcriptomic analysis in preclinical species is challenging due to the paucity of human liver data. Analyses based on conservation of biological properties (coalescent properties) across species, including co-expression modules, seemed a tractable approach that avoids the impracticality of sampling human subjects before and after drug administration.…”

A bibliometric analysis of micro/nano-bubble related research: current trends, present application, and future prospects

“…The drug and gene delivery applications can be realized to treat different kinds of diseases with the existence of microbubble techniques (Unger et al 2014). Liver-and myocardial-related research has presented a stable development momentum during the last 24 years, showing that the relatively potential approaches and techniques have been used to overcome liver-and myocardial-related issues (Narsinh et al 2011;Lomonaco et al 2013).…”

Nonalcoholic fatty liver disease: Diagnosis, pathogenesis, and management

“…However, liver-related diseases, such as cirrhosis, end-stage liver diseases, hepatocellular cancer, and liver transplantation, are being increased due to the obesity epidemic over time. We must divide patients with NAFLD into 2 groups according to follow-up results: patients with simple steatosis, which is a relatively benign condition, and NASH, in which liver0related mortality is increased (46). In light of the current knowledge, the basic principles for the management of NASH should be to decrease insulin resistance, to reduce visceral adiposity and fat mass, to decrease hyperlipidemia and hypertension, and to reduce oxidative stress and lipid peroxidation products (47).…”