Relationship between tetrahydrobiopterin and portal hypertension in patients with chronic liver disease

J Korean Med Sci. 2014 Mar;29(3):392-9. doi: 10.3346/jkms.2014.29.3.392. Epub 2014 Feb 27.

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Keywords: Hypertension, Portal; Liver Cirrhosis; Nitric Oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopterins / analogs & derivatives*
  • Biopterins / analysis
  • Chromatography, High Pressure Liquid*
  • Chronic Disease
  • Elasticity Imaging Techniques
  • Female
  • Hepatic Veins / physiology
  • Humans
  • Hypertension, Portal / complications
  • Hypertension, Portal / diagnosis*
  • Hypertension, Portal / metabolism
  • Liver / pathology
  • Liver Cirrhosis / diagnostic imaging
  • Liver Diseases / complications
  • Liver Diseases / diagnosis*
  • Liver Diseases / metabolism
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Portal Pressure
  • Regression Analysis
  • Severity of Illness Index

Substances

  • Biopterins
  • Nitric Oxide
  • sapropterin