Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis.

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.

• Authors: Karen Louise Thomsen, Francesco De Chiara, Krista Rombouts, Hendrik Vilstrup, Fausto Andreola, Rajeshwar P Mookerjee, Rajiv Jalan
• Journal: Medical hypotheses (Med Hypotheses) Vol. 113 Pg. 91-97 (Apr 2018) ISSN: 1532-2777 [Electronic] United States
• PMID: 29523305 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• Ammonia
• Urea

Topics

• Ammonia (metabolism, therapeutic use)
• Animals
• Biopsy
• Disease Models, Animal
• Disease Progression
• Fibrosis (prevention & control, therapy)
• Hepatic Stellate Cells (cytology)
• Humans
• Liver (metabolism)
• Models, Theoretical
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• Urea (chemistry)