Current and emerging pharmacological therapy for non-alcoholic fatty liver disease

Abstract

The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is life style modification including weight reduction and dietary regimen. Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis (NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an anti-oxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.

Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression

“…However, ezetimibe treatment did not ameliorate hepatic inflammation and fibrosis in patients with NAFLD and NASH [ 120 ]. Based on accumulated data, ezetimibe was suggested to affect only hepatocytes ballooning in NASH [ 121 ], but it is not recommended by the American and the European association of study of the liver.…”

Sheng-Jiang Powder Ameliorates High Fat Diet Induced Nonalcoholic Fatty Liver Disease via Inhibiting Activation of Akt/mTOR/S6 Pathway in Rats

“…But due to poor adherence to life style modification, finding new therapeutic agents to treat NAFLD or preventing its progression has attracted many interests. Statins and fibrates may help lower incidence of NAFLD in a small portion of cases via reducing blood cholesterol and triglycerides levels [ 20 ], there is still an urgent need to develop a new efficient approach for the management of NAFLD for majority of patients and now Chinese herbal medicine has garnered significant interest. According to the theory of traditional Chinese medicine, NAFLD belongs to the category of “Liver turbidity”.…”

The Association between Angiotensin II Type 1 Receptor Gene A1166C Polymorphism and Non-alcoholic Fatty Liver Disease and Its Severity

“… 40 Statins have been shown to be safe and effective for the treatment of NASH especially in those with other risks for cardiovascular disease. 41 - 43 Therefore, our findings are also important in clinical scenario and the association between AGTR1 gene A1166C and clinical response to treatment of NAFLD can be the topic for future studies. This study further emphasizes the important role of RAS in hepatic steatosis and supports targeting inhibition of renin-angiotensin pathway as a treatment option for NAFLD.…”