Iron and manganese homeostasis in chronic liver disease: relationship to pallidal T1-weighted magnetic resonance signal hyperintensity.

The hyperintense signal in the globus pallidus of cirrhotic patients on T1-weighted magnetic resonance (MR) imaging has been postulated to arise from deposition of paramagnetic manganese2+ (Mn). Intestinal absorption of both iron and Mn are increased in iron deficiency; iron deficiency may therefore increase susceptibility to Mn neurotoxicity. To investigate the relationships between MR signal abnormalities and Mn and Fe status, 21 patients with chronic liver disease were enrolled (alcoholic liver disease, 5; primary biliary cirrhosis, 9; primary sclerosing cholangitis, 3; hepatitis B virus, 2; hepatitis C virus, 1; alpha1-antitrypsin deficiency, 1). Signal hyperintensity in the pallidum on axial T1 weighted images (repetition time/evolution time: 500 ms/15 ms) was observed in 13 of 21 subjects: four patients had mild hyperintensity, three moderate, and six exhibited marked hyperintensity. Erythrocyte Mn concentrations were positively correlated with the degree of the MR hyperintensity (Kendall's tau-b=0.52, P<0.005). The log of erythrocyte Mn concentration was also inversely correlated with all measures of iron status: hemoglobin (Pearson's R=-0.73, P<0.0005); hematocrit (R=-0.62, P<0.005); serum Fe concentrations (R=-0.65, P<0.005); and TIBC saturation (R=-0.62, P<0.005). These findings confirm the association of Mn with the development of pallidal hyperintensity in patients with liver disease. We further found that iron deficiency is an exacerbating factor, probably because of increased intestinal absorption of Mn. We therefore recommend that patients with chronic liver disease avoid Mn supplements without concurrent iron supplementation.

Aprotinin efficacy on intraoperative bleeding and transfusion requirements in orthotopic liver transplantation.

BACKGROUND: Bleeding complications frequently occur during orthotopic liver transplantation (OLT), particularly in patients with liver cirrhosis. Enhanced fibrinolytic activity in plasma was seen to play a key role in the development of the hemostatic disorder and of hemorrhages. Aprotinin, a serine protease inhibitor, has been used in the prevention and/or treatment of hyperfibrinolytic states. STUDY DESIGN AND METHODS: In the present study, the effect of aprotinin on bleeding complications and transfusion requirements was investigated in OLT patients with liver cirrhosis. Seven consecutive cirrhotic patients undergoing OLT were infused with aprotinin following an original protocol (1,000,000-KIU intravenous loading dose plus 500,000 kallikrein-inhibitory units per hour until skin closure). Seven previous cirrhotic OLT patients not receiving aprotinin were used as controls. RESULTS: In the treated group, a significant decrease in the number of transfused units of packed red cells (48.7%, p < 0.01), fresh-frozen plasma (24.4%, p < 0.05), platelets (35.9%, p < 0.01), and autologous blood (55.2%, p < 0.01) was observed as compared with the control group. Moreover, the mean length of operation was significantly shorter in the aprotinin-infused patients than in untreated patients (8.3 +/- 1.2 vs. 10.1 +/- 1.8 hours, respectively; p < 0.01)). In the aprotinin-treated group, the antifibrinolytic efficacy was confirmed by the lack of increase in D-dimer levels and decrease of fibrinogen in plasma; on the contrary, these changes were always seen in the group not receiving aprotinin. CONCLUSION: Infusion of aprotinin during OLT in cirrhotic patients can be recommended for the prevention of hyperfibrinolysis-triggered bleeding, thus reducing transfusion requirements. A possible protective effect on the primary nonfunction of the grafted liver is suggested.

Cyclosporine and liver regeneration studied by in vivo 31P nuclear magnetic resonance spectroscopy.

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasively in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N = 2) as compared to either the normal (N = 2) or PCS + CsA-treated dogs (N = 3) (P less than 0.05). The intracellular pH temporarily decreased from 7.3 +/- 0.05 to 7.0 +/- 0.05 during the fructose challenge. The regenerative indexes were increased in the PCS + CsA group (P less than 0.01). These data obtained in vivo using 31P-NMR spectroscopy in the liver following a portacaval shunt, suggest that: (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo.

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)