Background and Aims: Metal overload contributes to neuronal oxidative stress, which has been strongly implicated in thepathogenesis of hepatic encephalopathy (HE). Further than manganese, liver prevents other metal overload by producing scavenger proteins, like Ceruloplasmin (Cp) and Transferrin (Tf).Cp is required for copper metabolism and for the oxidation of toxic ferrous iron into ferric iron, therefore permitting its transport in plasma by Tf in an equilibrate antioxidant Cp/Tf system. We aimedto investigate if alterations in metal homeostasis could play a role in HE pathogenesis. Methods: Seventeen normal controls (CON), 8 patients with chronichepatitis (CH), and 22 cirrhotics, further subdivided into 2 groupsaccording to the absence (NENC, 11 patients) or presence (ENC, 11 patients) of history and/or on-going signs of overt HE, wereenrolled. All patients and controls underwent:– determination of Cp, Cp activity, Tf, iron and total copper plasma concentrations, and of Tf saturation and Cp/Tf ratio;– cognitive evaluation with repeteable-battery-for-the-assessmentof-neuropsychological-status (RBANS); electroencephalography.A subgroup of patients was tested by specific MRI sequences in order to evaluate manganese and iron brain amount (Copper isparamagnetic). Results: In psychometry, cirrhotics performed worse with respectto CON and CH (p < 0.01), and ENC worse than NENC (p< 0.05).Specific EEG alterations were observed only in ENC, while other EEG alterations, compatible but not specific for HE, were observed in ENC and NENC (p < 0.01). Biochemical variables are reported in Table 1. Copper levels were significantly reduced in ENC, while ironconcentrations did not show significant changes. While showing nonsignificant fluctuations in CH and NENC, Cp, Cp activity, Tf, Tfsaturation and Cp/Tf ratio were significantly altered in ENC. MRI analysis showed iron and manganese basal ganglia overload in cirrhotic patients with respect to CON and CH (p < 0.05).
METAL METABOLISM IMPAIRMENT IN PATIENTS WITH HEPATIC ENCEPHALOPATHY
Vespasiani Gentilucci U;G Galati;F Ursini;M Tombini;L Quintiliani;F Vernieri;Picardi A
2012-01-01
Abstract
Background and Aims: Metal overload contributes to neuronal oxidative stress, which has been strongly implicated in thepathogenesis of hepatic encephalopathy (HE). Further than manganese, liver prevents other metal overload by producing scavenger proteins, like Ceruloplasmin (Cp) and Transferrin (Tf).Cp is required for copper metabolism and for the oxidation of toxic ferrous iron into ferric iron, therefore permitting its transport in plasma by Tf in an equilibrate antioxidant Cp/Tf system. We aimedto investigate if alterations in metal homeostasis could play a role in HE pathogenesis. Methods: Seventeen normal controls (CON), 8 patients with chronichepatitis (CH), and 22 cirrhotics, further subdivided into 2 groupsaccording to the absence (NENC, 11 patients) or presence (ENC, 11 patients) of history and/or on-going signs of overt HE, wereenrolled. All patients and controls underwent:– determination of Cp, Cp activity, Tf, iron and total copper plasma concentrations, and of Tf saturation and Cp/Tf ratio;– cognitive evaluation with repeteable-battery-for-the-assessmentof-neuropsychological-status (RBANS); electroencephalography.A subgroup of patients was tested by specific MRI sequences in order to evaluate manganese and iron brain amount (Copper isparamagnetic). Results: In psychometry, cirrhotics performed worse with respectto CON and CH (p < 0.01), and ENC worse than NENC (p< 0.05).Specific EEG alterations were observed only in ENC, while other EEG alterations, compatible but not specific for HE, were observed in ENC and NENC (p < 0.01). Biochemical variables are reported in Table 1. Copper levels were significantly reduced in ENC, while ironconcentrations did not show significant changes. While showing nonsignificant fluctuations in CH and NENC, Cp, Cp activity, Tf, Tfsaturation and Cp/Tf ratio were significantly altered in ENC. MRI analysis showed iron and manganese basal ganglia overload in cirrhotic patients with respect to CON and CH (p < 0.05).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
