Pharmacotherapy for Nonalcoholic Fatty Liver Disease

Abstract

Life style modifications and optimization of the management of cardio-metabolic comorbidities are currently the mainstay of treatment for patients with non-alcoholic fatty liver disease (NAFLD). Pharmacotherapy to halt or reverse hepatic histological injury and prevent the development of end stage liver disease is specifically offered to patients with non-alcoholic steatohepatitis (NASH) and those with advanced fibrosis. In this review, we will discuss state of the art of various pharmacological agents for NASH. The efficacy of vitamin E and pioglitazone is reasonably well established in a select group of patients with NASH. Current data do not offer convincing evidence for efficacy of pentoxifylline, long-chain polyunsaturated fatty acids, angiotensin receptor blockers, metformin or ursodeoxycholic acid. We also discuss the state of several emerging agents for treating NASH including the farsenoid X receptor (FXR) ligand, obeticholic acid.

SAF score and mortality in NAFLD after up to 41 years of follow-up

“…There are several on-going clinical studies for NASH, ranging from early phase 1, to large, multi-national phase 3 studies (20,21). Inclusion criteria for these studies include a NAS of four or greater, ignoring some patients with a phenotype that might have significant fibrosis, but low levels of NAS.…”

Linking Pathogenic Mechanisms of Alcoholic Liver Disease With Clinical Phenotypes

“…These provide an opportunity to evaluate compounds that might have effects in patients with ALD as well, given their similarities in histopathology. One example is the FXR agonist obeticholic acid 115 . This agent has been shown to have effect in patients with NASH.…”

Hepatic structural enhancement and insulin resistance amelioration due to AT1 receptor blockade

“…Conversely, AT2R has anti-inflammatory effects, mainly by down-regulating tumoral necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa B (NF-KB) pathways and by exerting anti-fibrogenic properties, besides reducing oxidative stress and cell proliferation[17,18]. Bearing this in mind, the angiotensin receptor blockers (ARBs) represents an evolution of the ACE inhibitors as they block exclusively the actions mediate by the interaction of ANG II with the AT1R[19,20]. Thus, important physiological effects stemmed from ANG II interaction with AT2R are maintained, leading to reduced atherogenesis, greater cardiac and endocrine pancreas functions, reduced glomerulosclerosis and fatty liver[21,22].…”