From the Guidelines
Ammonia levels increase in liver cirrhosis primarily due to the liver's impaired ability to convert ammonia to urea for excretion, a process further complicated by portal hypertension and reduced glutamine synthetase production. This condition is exacerbated by the liver's decreased capacity for glycogen storage and the subsequent predominance of catabolism, where protein is broken down for gluconeogenesis, as noted in the 2020 guidelines for liver cirrhosis management 1. The imbalance of amino acids, with lower concentrations of branched-chain amino acids (BCAAs) like valine, leucine, and isoleucine, and higher concentrations of aromatic amino acids in the blood of cirrhotic patients, contributes to the accumulation of ammonia. BCAAs play a crucial role in muscle metabolism, leading to glutamine production, which is essential for detoxifying ammonia.
Key factors contributing to increased ammonia levels in liver cirrhosis include:
- Impaired liver function due to scarring and loss of liver tissue
- Portal hypertension leading to portosystemic shunts
- Reduced production of glutamine synthetase
- Imbalance of amino acids, with decreased BCAAs and increased aromatic amino acids
- Increased catabolism for gluconeogenesis due to decreased glycogen storage capacity
The management of hyperammonemia in liver cirrhosis may involve strategies to reduce ammonia production or enhance its removal, such as dietary modifications, lactulose therapy, and, as suggested by recent guidelines, the potential use of oral BCAAs as an ancillary pharmacological option to manage hepatic encephalopathy 1. However, the effectiveness of such interventions can vary, and their implementation should be guided by the most current clinical evidence and the individual patient's condition.
From the Research
Ammonia Levels in Liver Cirrhosis
- Ammonia levels increase in liver cirrhosis due to the liver's reduced ability to detoxify ammonia, leading to its accumulation in the blood 2, 3.
- The urea cycle, which is responsible for removing ammonia from the body, is impaired in liver cirrhosis, resulting in hyperammonemia 3.
- Hyperammonemia is a major factor involved in the pathogenesis of hepatic encephalopathy (HE), a complication of liver cirrhosis characterized by brain dysfunction 2, 3.
Factors Contributing to Increased Ammonia Levels
- Portosystemic shunting, which allows ammonia-rich blood to bypass the liver and enter the systemic circulation, contributes to hyperammonemia in liver cirrhosis 4.
- Renal ammonia production also plays a role in increasing ammonia levels in patients with liver cirrhosis 4.
- Protein intake can increase ammonia levels, as amino acid metabolism produces ammonia 5.
Clinical Implications
- Measuring ammonia levels can provide useful clinical guidance for the diagnosis of HE and offers prognostic information in patients with liver cirrhosis 6.
- Ammonia levels can define a therapeutic target, and alleviating ammonia toxicity is essential in the treatment of HE 2, 6.
- However, the role of ammonia in guiding HE diagnosis, staging, and treatment is still unclear, and its use in clinical practice is debated 6.