How can poor appetite contribute to the development of hepatic encephalopathy?

From the Guidelines

Poor appetite can significantly contribute to the development of hepatic encephalopathy by leading to malnutrition, which in turn causes metabolic disturbances, including deficiencies in essential nutrients and impaired liver function, ultimately resulting in elevated ammonia levels and brain dysfunction. This is supported by the ESPEN guideline on clinical nutrition in liver disease, which states that nutrition therapy should be offered to all patients with severe liver disease who cannot meet their nutritional requirements through spontaneous food intake, in order to improve survival, infection rate, liver function, and resolution of encephalopathy 1. The guideline emphasizes the importance of adequate calorie and protein intake, highlighting that reduced caloric intake is associated with higher mortality and higher complication rates.

Key factors contributing to the development of hepatic encephalopathy in the context of poor appetite include:

• Malnutrition, which is prevalent in the majority of patients with severe liver disease, and is an independent predictor of mortality 1
• Protein deficiency, which reduces the liver's ability to clear ammonia from the blood, leading to elevated ammonia levels and hepatic encephalopathy 1
• Hypoglycemia, which directly impairs brain function since glucose is the brain's primary energy source
• Electrolyte imbalances, particularly sodium, potassium, and magnesium abnormalities, which further disrupt normal brain activity

The EASL clinical practice guidelines on nutrition in chronic liver disease provide further insight into the relationship between malnutrition and hepatic encephalopathy, highlighting that muscle plays an important role in ammonia removal and that sarcopenia is an independent risk factor for the development of hepatic encephalopathy 1. The guidelines recommend that patients with hepatic encephalopathy should avoid long periods of fasting and should be encouraged to split their caloric and protein intake into small, frequent meals. Additionally, the guidelines suggest that nutritional intervention, including a diet with a normal protein content and adequate calorie intake, can improve neuropsychiatric performance in patients with minimal hepatic encephalopathy and decrease their risk of developing overt hepatic encephalopathy 1.

In terms of treatment, addressing the underlying cause of poor appetite and providing appropriate nutritional support is crucial, which may include thiamine supplementation, correction of electrolyte abnormalities, and ensuring adequate protein and calorie intake 1. The use of branched-chain amino acid (BCAA) supplements may also be beneficial in patients with hepatic encephalopathy, particularly those who are intolerant to meat protein, as they can facilitate the provision of an adequate nitrogen intake and may have nutritional value 1. However, the evidence for the use of BCAA supplements is limited, and their effects on mortality, quality of life, and nutritional status are unclear 1.

From the Research

Poor Appetite and Hepatic Encephalopathy

• Poor appetite can contribute to the development of hepatic encephalopathy through malnutrition and thiamine deficiency, as seen in Wernicke-Korsakoff syndrome 2.
• Thiamine deficiency can cause a range of symptoms, including loss of appetite, confusion, and delirium, which can progress to Wernicke encephalopathy and eventually Korsakoff syndrome 2, 3.
• Malnutrition and parenteral nutrition without thiamine supplementation can lead to Wernicke's encephalopathy, as reported in a case study of a patient with cerebral infarction 4.
• Poor appetite is a common problem in older people and can contribute to weight loss, nutritional deficiencies, and poor healthcare outcomes, including increased mortality 5.
• Thiamine deficiency can also cause lactic acidosis and neurological symptoms, which can be treated with thiamine injection 6.

Mechanisms and Risk Factors

• Thiamine deficiency is a key factor in the development of Wernicke encephalopathy, and poor appetite can contribute to this deficiency by reducing food intake and nutrient absorption 2, 3.
• Other risk factors for Wernicke encephalopathy include alcohol addiction, bariatric surgery, hyperemesis gravidarum, and anorexia nervosa 2.
• Malnutrition and parenteral nutrition without thiamine supplementation can also increase the risk of Wernicke encephalopathy 4.
• Early recognition and treatment of thiamine deficiency are crucial to prevent the development of Wernicke encephalopathy and improve patient outcomes 3, 4, 6.