Abstract
BACKGROUND: Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. METHODS: Forty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m(2) were included (median BMI: 10.51 kg/m(2) on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the "estimated liver weight/ideal body weight" was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days. RESULTS: Liver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13-18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m(2)) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m(2)). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20-25 kcal/kg/day), increasing to 700-800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia. CONCLUSIONS: Liver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided.