Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension

Authors

  • Manuel Hernández-Guerra,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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    • Manuel Hernández-Guerra and Juan C. García-Pagán made equal contributions and share first authorship.

  • Juan C. García-Pagán,

    Corresponding author
    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
    • Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, C/Villarroel 170, Barcelona 08036, Spain
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    • Manuel Hernández-Guerra and Juan C. García-Pagán made equal contributions and share first authorship.

    • fax: (34)-93-2279856

  • Juan Turnes,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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  • Pablo Bellot,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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  • Ramón Deulofeu,

    1. Clinical Biochemistry Laboratory, Hospital Clinic, Barcelona, Spain
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  • Juan G. Abraldes,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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  • Jaime Bosch

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d′Investigaciones Biomédiques August Pi i Sunyer, Barcelona, Spain
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  • Potential conflict of interest: nothing to report.

Abstract

Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow-dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO). Ascorbic acid reverts endothelial dysfunction in other vascular disorders, via the increase of NO bioavailability through the neutralization of superoxide anions, thus preventing the scavenging of NO by superoxide. This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis. Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics, ascorbic acid, and malondialdehyde (MDA). Patients were randomly allocated to receive ascorbic acid (3 g, intravenously, n = 15) or placebo (n = 12) followed by a liquid meal. A third group received ascorbic acid followed by a sham meal (n = 10). Measurements were repeated after 30 minutes (hepatic venous pressure gradient at 15 and 30 minutes). Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls. Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient (4% ± 7% vs. 18% ± 10% in placebo at 30 minutes, P < .001). Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics. In conclusion, patients with cirrhosis exhibited intrahepatic endothelial dysfunction, associated with decreased levels of ascorbic acid and increased levels of MDA. Ascorbic acid improved intrahepatic endothelial dysfunction, blunting the postprandial increase in portal pressure. These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension. (HEPATOLOGY 2006;43:485–491.)

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