J Korean Med Sci.  2014 Mar;29(3):392-399. 10.3346/jkms.2014.29.3.392.

Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease

• Hong WK
• Shim KY
• Baik SK
• Kim MY
• Cho MY
• Jang YO
• Park YS
• Han J
• Kim G
• Cho YZ
• Hwang HW
• Lee JH
• Chae MH
• Kwon SO

• KMID: 1734927
• DOI: http://doi.org/10.3346/jkms.2014.29.3.392

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.

Keyword

Hypertension, Portal; Nitric Oxide; Liver Cirrhosis

MeSH Terms

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

Figure

• 

  Fig. 1 Linear regression analysis between HVPG (mmHg) and BH4 (pM/mg). There was no significant correlation between HVPG and BH4 (r2 = 0.023, P = 0.036). HVPG, hepatic venous pressure gradient; BH4, tetrahydrobiopterin.

• 

  Fig. 2 Correlation between Laennec scoring system and BH4 levels. There was no significant correlation between hepatic fibrosis subclassification according to the Laennec scoring system and BH4 (P = 0.867). BH4, tetrahydrobiopterin.

• 

  Fig. 3 Relationship between BH4 and clinical outcomes. (A) Relationship between Child-Pugh Class and BH4. There was no significant correlation between Child-Pugh Class and BH4 (P = 0.26). (B) Relationship between clinical stage of cirrhosis and BH4. There was no significant correlation between clinical stage of cirrhosis and BH4 (P = 0.405). BH4, tetrahydrobiopterin.

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  Fig. 4 Relationship between HVPG and Laennec fibrosis scoring system. A statistically significant relationship was observed between HVPG and hepatic fibrosis subclassification using the Laennec fibrosis scoring system (P < 0.001). HVPG, hepatic venous pressure gradient.

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