Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis. (April 2018)

• Record Type: Journal Article
• Authors: Thomsen, Karen Louise; De Chiara, Francesco; Rombouts, Krista; Vilstrup, Hendrik; Andreola, Fausto; Mookerjee, Rajeshwar P.; Jalan, Rajiv
• Is Part Of: Medical hypotheses. Volume 113(2018)
• Page Start: 91
• Page End: 97
• Publication Date: 2018-04
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Medicine; Periodicals; 610
• DOI: 10.1016/j.mehy.2018.02.010
• Languages: English
• ISSNs: 0306-9877

Abstract

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage. Ammonia has been shown to activate HSCs in vivo and in vitro . Hyperammonemia in the context of NASH may therefore favour the progression of fibrosis and the disease. We therefore hypothesise that ammonia is a potential target for prevention of fibrosis progression of patients with NASH.