Trace Element Imbalances in Acquired Hepatocerebral Degeneration and Changes after Liver Transplant

SIMPLE SUMMARY: The liver is responsible for the metabolism and elimination of many deleterious substances from the human body. Consequently, toxic substances can accumulate in patients with chronic liver disease, particularly in those with surgically or spontaneously induced portosystemic shunts. So-called acquired hepatocerebral degeneration (AHD) is associated with the accumulation of manganese, a trace element, in the brain of patients with liver disease. The symptoms include movement disorders and cognitive impairment. Liver transplantation (LT) is the only available treatment. In this study, we evaluated the blood levels of trace elements in patients with AHD before and after LT and compared them with those of healthy controls. The association between trace element levels and changes in the neurological examination was also assessed. The impact of LT on clinical and analytical variables was evaluated in a subgroup of patients. We found significantly different levels of many trace elements, and they were generally higher in AHD patients compared to those of the controls, although they were still within normal reference ranges. Some trace elements linked to oxidative stress and inflammation (e.g., zinc, copper and selenium) were particularly affected in patients, suggesting a putative role in the pathophysiology and symptomatology of AHD. The neurological symptoms and trace element imbalances were at least partially reversible after LT. ABSTRACT: Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.