Liver Stiffness Predicts Portal Hypertension in HCV Cirrhosis

FLORENCE, Italy, May 3 -- An ultrasound measurement of liver thickness -- also known as liver stiffness -- predicted portal hypertension in patients with hepatitis C-related cirrhosis, researchers here found.

In a comparison with the standard technique, measuring the hepatic venous pressure gradient, there was a statistically significant positive correlation between the ultrasound technique and the gradient measurement.

Nevertheless, the positive correlation applied only to hepatic venous pressure gradient levels of less than 10 or 12 mm Hg, Massimo Pinzani, M.D., Ph.D., of the University of Florence, and colleagues, reported in the May issue of Hepatology.

Although pressure gradient measurement is the gold standard for assessing portal hypertension, the technique is invasive, expensive, and requires technical expertise found only in large tertiary care centers, Dr. Pinzani said.

In search of a better method, the researchers evaluated transient elastography, a rapid, noninvasive ultrasound technique, to measure liver stiffness, and compared its accuracy with that of measuring hepatic venous pressure gradients.

In transient elastography, the tip of an ultrasound probe is placed between two intercostal spaces at the level of the right lobe of the liver. A low-amplitude vibration induces an elastic shear wave throughout the liver tissue. Pulse-echo ultrasound permits measurement of wave velocity, which corresponds directly with liver stiffness across the organ, reflecting a larger sample than liver biopsy.

From March 1, 2005 to July 1, 2006, 61 patients (ages 32 to 75) with diagnosed or suspected cirrhosis from chronic HCV infection underwent transient elastography, followed by a hepatic venous pressure gradient measurement and liver biopsy. Patients with a body mass index of 35 kg/m² or higher were excluded.

Overall, a strong relationship between liver stiffness and pressure gradient measurements was found in the total population (r = 0.81, P < 0.0001).

However, although the correlation was excellent for pressure gradient values less than 10 mm Hg or less than 12 mm Hg (r=0.81, P < 0.0003 and r = 0.91, P < 0.0001, respectively), linear regression analysis was not optimal for values ?10 mm Hg (r² = 0.35, P < 0.0001) or ?12 mm Hg (r² =0.17, P=0.02).

The researchers also noted a correlation between liver stiffness and the presence of esophageal varices (P =0.002), although the negative and positive predictive values for their detection were unsatisfactory, at 66% and 77% in a population where the prevalence of varices was 64% (30 of 47 patients), respectively, they said.

Moreover, they added, this study failed to demonstrate a correlation between liver stiffness and the size of esophageal varices.

The researchers noted that whereas the correlation between the two measurements seemed optimal only for hepatic venous pressure gradient values less than 10 and 12 mm Hg, this important observation suggests that beyond a certain degree of portal pressure, the development of portal hypertension becomes at least partially independent of the simple accumulation of the fibrillar extracellular matrix responsible for the increase in liver stiffness.

The measurement of liver stiffness by this ultrasound technique may represent a reliable non-invasive method for screening patients to be given standard testing, including upper GI endoscopy and hemodynamic studies, the researchers said, However, they added, the technique is not good enough to replace endoscopy for detection of esophageal varices.

Finally, they noted, these results need to be validated in larger populations, especially among those patients with a body mass index greater than 30 kg/m² for whom liver stiffness reproducibility may not be optimal.

In an accompanying editorial, Joseph K Lim, M.D., and Roberto J. Groszmann, M.D., of Yale , praised the study as the first to evaluate the correlation between liver stiffness and clinically significant portal hypertension, as reflected by both direct pressure gradient measurement and identification of esophageal varices on upper GI endoscopy.

However, to date, they said, direct measurement of hepatic venous pressure gradient remains the gold standard for the diagnosis and staging of portal hypertension.

Although the use of noninvasive modalities is attractive, additional validation studies measuring diagnostic accuracy in a representative American population are needed prior to regulatory approval, they wrote.

Of note, they said, the mean BMI of patients in this study was 23, and those with a BMI of 35 kg/m² or greater were excluded, which contrasts with the higher means reported in large U.S. trials for HCV therapy.

Liver-stiffness measurement represents one of several noninvasive tools that appear to be useful in diagnosing and staging liver fibrosis in selected patients, although the current data supporting its role in evaluating the consequences of portal hypertension remain unconvincing, Drs. Lim and Groszmann said.

"Additional data in carefully designed studies will help define its appropriate role in clinical practice," they added.