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

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.

Hepatic venous pressure gradient: clinical use in chronic liver disease

Portal hypertension is a severe consequence of chronic liver diseases and is responsible for the main clinical complications of liver cirrhosis. Hepatic venous pressure gradient (HVPG) measurement is the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >10 mmHg. In this condition, the complications of portal hypertension might begin to appear. HVPG measurement is increasingly used in the clinical fields, and the HVPG is a robust surrogate marker in many clinical applications such as diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who had a reduction in HVPG of > or =20% or to < or =12 mmHg in response to drug therapy are defined as responders. Responders have a markedly decreased risk of bleeding/rebleeding, ascites, and spontaneous bacterial peritonitis, which results in improved survival. This review provides clinical use of HVPG measurement in the field of liver disease.

Non invasive prediction of varices in Egyptian cirrhotic patients

Cirrhotic patients frequently undergo screening endoscopy for the presence of varices. In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aim was to develop a predictive model using independent risk factors for the presence of varices in the enrolled patients. 200 patients with liver cirrhosis with no history of variceal haemorrhage were subjected to clinical examination; laboratory investigations [CBC, Liver biochemical profile, serum urea and creatinine], modified Child-Pugh score and MELD score were calculated. Abdominal ultrasonography and Doppler study of the portal and splenic veins studying the liver size, the presence of periportal thickening, hepatic veins flow pattern, the splenic longest axis and volume, the presence of ascites and collaterals. Portal vein and splenic vein diameter, patency, cross sectional area, mean flow velocity, blood flow volume congestion index and direction of flow of portal vein were calculated. Platelets count/Splenic diameter ratio and Right liver lobe diameter/ albumin ratio were calculated for all patients. Upper endoscopy was done where oesophageal varices were graded according to modified Thakeb classification. This study revealed that 83% of patients had oesophageal varices; 52% had small sized oesophageal varices and 31% had large sized oesophageal varices. In patients with varices; 12% had biphasic and 22.9% had monophasic hepatic veins flow pattern, with p value of 0.002. Portal vein direction of flow was bidirectional in 22.9% and Hepatofugal in 9.6% with a p value of 0.004. The portal vein velocity of 9.3 +/- 2.3cm/ sec with a p value of <0.001 and the ascites was present in 77% of patients with a p value of 0.005. In patients with large sized varices; shrunken liver was present in 83.1% of patients with a p value of 0.005 and serum albumin <2.5gm/dl with a p value of 0.008. Hepatic veins flow pattern [biphasic and monophasic], portal vein direction of flow [hepatofugal and bidirectional], decreased portal vein velocity and the presence of ascites [moderate and marked] were the significant variables for prediction of presence of varices. Shrunken liver and the low serum albumin were the significant variables for prediction of large varices

Hepatic venous pressure gradient measurement: time to learn!

Portal hypertension is a clinical syndrome defined by a pathological increase in portal pressure. The development of cirrhosis of the liver is characterized by clinical manifestations related to portal hypertension like esophageal varices, ascites, bleeding, and encephalopathy. Direct measurement of portal pressure is invasive, inconvenient, and clinically impractical. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. When blood flow in a hepatic vein is stopped by a wedged catheter, the proximal static column of blood transmits the pressure from the preceding communicated vascular territory (hepatic sinusoids) to the catheter. Thus, WHVP reflects hepatic sinusoidal pressure and not the portal pressure itself. In the normal liver, due to pressure equilibration through interconnected sinusoids, wedged pressure is slightly lower than portal pressure, though this difference is clinically insignificant. In liver cirrhosis, the static column created by balloon inflation cannot be decompressed at the sinusoidal level due to disruption of the normal intersinusoidal communications; therefore, WHVP gives an accurate estimation of portal pressure in cirrhosis. The normal HVPG value is between 1 to 5 mmHg. Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence. HVPG >or= 10 mmHg (termed clinically significant portal hypertension) is predictive of the development of complications of cirrhosis, including death. HVPG above 12 mmHg is the threshold pressure for variceal rupture. The main advantages of HVPG are its simplicity, reproducibility, and safety. This review summarizes the technique of the HVPG measurement.