Hepatic encephalopathy is related to anemia and fat-free mass depletion in liver transplant candidates with cirrhosis

Background. Although muscle wasting may lead to decreased ammonia detoxification in cirrhosis, the potential role of lean mass depletion in hepatic encephalopathy (HE) has not been explored. Anemia, hormonal abnormalities, and psychological distress may contribute to cognitive dysfunction, but data on their potential relation to HE are limited. Methods. Data on 108 cirrhotic liver transplant candidates enrolled in a prospective study on fatigue were retrospectively analyzed. HE was assessed clinically and with the number connection tests (NCT) A and B. Psychosocial distress was assessed with a validated questionnaire. Fasting serum glucose, insulin, ammonia, and the glomerular filtration rate (GFR) were measured. Fat and fat-free mass was evaluated with dual-energy X-ray absorptiometry. Serum cortisol, testosterone, dehydroepiandrosterone, thyroid function tests, interleukin-6, and tumor necrosis factor-α (TNF-α) were measured in a subgroup of 80 patients. Results. A total of 28% of patients had (overt or minimal) HE. Anemia was present in 59%, diabetes in 29%, renal impairment in 16%, and fat-free mass depletion in 14%. In multivariate analysis, fat-free mass depletion was an independent predictor of HE and NCT-A; renal impairment of NCT-A and-B; and anemia of NCT-B (p < 0.05 for all). HE was also independently related to international normalized ratio and TNF-α (p < 0.05 for both), but not to other hormonal abnormalities or psychological distress. Plasma ammonia was independently associated to anemia (beta = 15.24, p = 0.049), fasting insulin (beta = 0.26, p < 0.05), and GFR (beta =-0.43, p = 0.003). Conclusions. Anemia and fat-free mass depletion are predictors of HE in cirrhotic liver transplant candidates along with liver failure, renal impairment, and systemic inflammation.