Hepatic venous pressure gradient in 2010: Optimal measurement is key
Authors: Andrew K. Burroughs, Ulrich Thalheimer
Journal: Hepatology (2010)

The first documented attempt to measure portal venous pressure was made over 110 years ago in a dog: a cannula was inserted into the mesenteric vein, and it was connected to a water manometer.1 Over the next 5 decades, portal pressure could be measured in human beings only by invasive procedures such as direct portal vein catheterization and splenic pulp pressure measurements. In 1951, an indirect measurement method was described2 in which a small catheter was advanced into the hepatic vein and wedged so that it could not be advanced any further, and this formed a continuous static column of blood between the catheter and the hepatic sinusoids. This wedged hepatic vein pressure (WHVP) equals the pressure in the hepatic sinusoids, which in turn corresponds to the portal vein pressure (in the absence of presinusoidal portal hypertension). Several studies have assessed the direct correlation of WHVP to portal vein pressure and have documented very good concordance.3 To eliminate variations in abdominal pressure, such as those occurring with ascites, the free hepatic vein pressure (FHVP; i.e., the unwedged pressure in the hepatic vein) is currently used as an internal zero reference. The difference between WHVP and FHVP—the hepatic venous pressure gradient (HVPG)—is a measure of the severity of portal hypertension. In 1979, the measurement of WHVP was modified by the use of a balloon occlusion catheter, which yields a more reproducible measurement as it allows a more uniform and greater area of occlusion of the sinusoidal bed.4 The occluded wedge hepatic venous pressure also correlates very well to portal vein pressure.3 In 2004, the optimal technique for measuring HVPG was well described.5 In 1987, one of us suggested that HVPG was underused as a prognostic test in chronic liver disease.6 Since then, many studies have shown its strong predictive power for mortality, which notably is independent of the severity of liver disease as measured by the Child-Pugh or Model for End-Stage Liver Disease scores but improves their predictive power when it is combined with them.7 HVPG also predicts the advent of complications of cirrhosis. Patients with an HVPG below 10 mm Hg have a 90% chance of not decompensating over the next 4 years.8 Varices develop only at an HVPG greater than 10 mm Hg9 and bleed at an HVPG greater than 12 mm Hg.10 In patients with acute variceal hemorrhage, an HVPG ≥ 20 mm Hg is associated with worse outcomes and identifies patients who would benefit from early transjugular intrahepatic portosystemic shunt (TIPS) placement11-13 or other therapies.14 An HVPG ≤ 10 mm Hg identifies patients with Child A cirrhosis who are likely to obtain excellent outcomes after curative resection of hepatocellular carcinoma. Our group and others have proposed HVPG measurement as an important marker in assessing prognosis and fibrosis in patients with chronic viral hepatitis.15 This has been shown to be useful after liver transplantation for HCV-related cirrhosis16, 17 and for chronic hepatitis B–related cirrhosis after antiviral treatment.18 FHVP, free hepatic vein pressure; HAPG, hepato-atrial pressure gradient; HVPG, hepatic venous pressure gradient; RAP, right atrial pressure; TIPS, transjugular intrahepatic portosystemic shunt; WHVP, wedged hepatic vein pressure. Changes in HVPG after pharmacological intervention have been used to define an optimal hemodynamic response, which is a reduction of HVPG of ≥20% from the baseline or to <12 mm Hg. This predicts a low risk of future bleeding in both primary and secondary prophylaxis. However, even patients who do not achieve these targets have some protection from bleeding.19, 20 Importantly, lesser reductions in HVPG21 are also associated with a reduction in both mortality and other complications of cirrhosis, such as spontaneous bacterial peritonitis22 and encephalopathy,23, 24 which can be independent of any concomitant improvement in liver function.25 The aforementioned studies demonstrate the utility of measuring HVPG. Thus, the appropriate and correct measurement of HVPG is an important issue both in clinical research and with more widespread use, as has been repeatedly advocated.5-7, 26 In this issue of HEPATOLOGY, La Mura and colleagues27 provide data that are helpful in further standardizing the technique of HVPG measurements. The authors assessed whether the right atrial pressure (RAP) might be a better internal reference zero standard than FHVP. RAP has been considered better than FHVP for technical reasons because sometimes partially wedged FHVP readings can be obtained.28 It is often used as the internal zero reference by radiologists, particularly if TIPS is in situ. Pathophysiologically, RAP might also take into account the collateral flow reaching the superior vena cava from the azygos vein, which takes the main drainage from the gastroesophageal collateral plexus, including that from varices. Thus, RAP might reflect, as a surrogate, the pressure in the varix more closely. Azygos blood flow is always reduced with nonselective beta blockers, but this effect is not measured by HVPG. Thus, RAP could be a better reference point when we are assessing changes in portal vein pressure.20 La Mura and colleagues27 compared the measurement of HVPG with the gradient between WHVP and RAP [the hepato-atrial pressure gradient (HAPG)] in 154 patients with varices and an HVPG ≥12 mm Hg who were enrolled in previous trials of primary or secondary prophylaxis for variceal bleeding. They also evaluated the relationship between portocaval and porto-atrial gradients in 99 patients with TIPS. In the 154 patients, the agreement between HVPG and HAPG was only modest both at the baseline and during treatment with nonselective beta blockers. Most importantly, the prognostic value of HVPG reduction with respect to the risk of bleeding was not improved by HAPG. An interesting finding was that even though nonselective beta blockers are known to reduce venous vascular compliance, FHVP did not increase as would be expected, whereas RAP did show an increase. In the TIPS cohort, the agreement between portocaval and porto-atrial gradients again was not good. Indeed, if HAPG had been used to assess the optimal reduction in portal pressure after TIPS (≤12 mm Hg), then 20% of the patients would have had unnecessary further dilatations and possibly been placed at greater risk of encephalopathy. Thus, RAP cannot substitute for FHVP when one is measuring HVPG and does not sufficiently reflect changes in collateral blood flow and venous compliance, surrogates of which could improve the prognostic information provided by HVPG. An alternative could be variceal pressure measurement, which might incorporate a surrogate measure of collateral blood flow, but it is not routinely or reliably measured in clinical practice.29 At present, HVPG measurement is the best surrogate of portal pressure and also the best single prognostic marker available for patients with cirrhosis.7 Recent studies have suggested further applications. In patients likely to bleed from varices, an acute response to intravenous propranolol assessed during a single interventional session30, 31 might obviate the repeated measurement performed 1 to 3 months after the baseline measurement.19 HVPG has a strong predictive association with the development of hepatocellular carcinoma.32 Lastly, in the evaluation of fibrosis, HVPG, combined with new imaging techniques in histopathology,33 should help to subdivide cirrhosis into further stages34: an HVPG ≥ 10 mm Hg already defines clinically significant portal hypertension8 when complications of cirrhosis are likely to occur. The measurement of HVPG, whether performed by radiologists or hepatologists,35 should already be standard clinical practice in specialized liver centers and should be coupled with appropriate quality control for the continued practice of the optimal technique. An added bonus of HVPG measurement is that transjugular liver biopsy can be performed at the same time.36 This is a safe procedure36; four cores provide optimal specimens even for staging chronic viral hepatitis,37 and the different cores reduce sampling variability found in the single core of standard percutaneous biopsies.38 This study by La Mura and colleagues27 adds further information about the correct method for measuring HVPG. It is hoped that this study in 2010 will provide a further stimulus, added to previous ones,3-8 for measuring HVPG in the clinical practice of hepatology. The findings provide evidence that FHVP and not RAP should be used as the internal zero reference in all patients. Thus, units not using this optimal method should change their practice, and units considering setting up HVPG measurement should follow the published technique.5