Clinical significance of the latency period of abnormal ammonia metabolism in chronic liver disease: Proposal of a new concept

The liver is a key organ in regulating metabolism, and chronic liver disease is associated with several metabolic disorders. In the later stages of liver cirrhosis, the urea cycle is impaired, which disrupts of ammonia detoxification and eventually causes hyperammonemia and hepatic encephalopathy. Although hyperammonemia is not detected during the period between the late stage of chronic hepatitis and the early stage of liver cirrhosis, hepatic albumin synthesis capacity decreases as the fibrosis progresses. Increased ammonia levels are associated with a decreased capacity of the liver to synthesize albumin as well as activation of hepatic stellate cells, which promote fibrosis. Herein, we discuss the possibility that abnormal ammonia metabolism might play an important role in the pathogenesis of liver diseases even without hyperammonemia. We consider the disease period without hyperammonemia as the latency period of abnormal ammonia metabolism and discuss its clinical significance.