Targeting portal pressure measurements: A critical reappraisal

Abstract

O ver the last two decades, our understanding of the treatment and prognosis of portal hypertension has continued to improve. 1,2 The use of techniques to measure the wedged hepatic venous pressure (WHVP), developed more than 50 years ago, has played a major role in elucidating the pathophysiology of the syndrome 3 and, consequently, in developing currently available pharmacologic therapy. Recently, a role for measurements of WHVP has also been proposed in evaluating the progression of chronic liver diseases. 4 This measurement has been shown to be the best predictor of the development of complications of portal hypertension in patients with early cirrhosis. 5 Investigators in this area of research need not be convinced about the importance of the WHVP technique in advancing our knowledge of portal hypertension from the experimental arena 3 to current clinical applications. 6 -8 However, there is an unanswered question that has lingered with us for more than 20 years: Should measurement of WHVP be incorporated into clinical practice?To begin to answer this question, we must assure ourselves that the technique is executed properly. In a recent study performed to evaluate a new pharmaceutical agent, one of us (R.J.G.) was asked to be a blind reviewer of WHVP tracings performed by centers experienced in the measurement of WHVP. Even though minimal criteria for acceptable measurements have been established (Table 1), approximately 30% of studies% had to be rejected as the tracings obtained were uninterpretable. Our experience is not unique (Jaime Bosch, personal communication). We cannot draw conclusions about the usefulness of this technique in a clinical setting if investigational studies designed to answer the question do not themselves comply with minimal criteria for technical adequacy. To achieve results that are consistent and comparable from center to center, meticulous attention to detail is required ( Table 1).Direct measurement of portal venous pressure (PVP) is invasive and inconvenient. In 1951, Myers and Taylor 9 first described WHVP, which is the measurement of the sinusoidal pressure, an indirect measurement of PVP. Since then, WHVP has been shown to be very safe and the rate of successful hepatic vein catheterization is greater than 95%. By threading a small catheter into a hepatic vein until it cannot be advanced further, a "wedged" hepatic venous pressure is obtained. As the hepatic vein is occluded, a continuous column of fluid between the catheter and the sinusoid is formed, resulting in a pressure reading that is equal to the sinusoidal pressure (Fig. 1). In normal livers, the low-resistant sinusoidal network dissipates most of the pressure back up from the wedged catheter. As there is no direct connection, via a static column of fluid, between the catheter and the portal tributaries, the pressure reading of the transducer reflects sinusoidal pressure (in normal livers is slightly lower than portal pressure). This is also observed in presinusoidal causes of portal hypertension such as schisto...

Wedged hepatic vein pressure (WHVP): Ready for prime time

“…A fall of the hepatic venous pressure gradient (WHVP-free hepatic vein pressure [HVPG]) by 20% or to less that 12 mm Hg following pharmacologic therapy is associated with much greater reduction in the risk of bleeding and improved survival as compared to those who lacked this hemodynamic response. [3][4][5][6] Hemodynamic responders appear less likely to develop other complications of cirrhosis as well. 7 Also, a high HVPG (Ͼ20 mm Hg) at the time of presentation of variceal bleeding is associated with a poor outcome as compared to patients with lower pressures.…”

“…8 Despite the consistency of the reported series on the importance of measuring the HVPG in determining risk of variceal bleeding or rebleeding, numerous problems with the published studies exist, especially the absence of prospective data demonstrating that using the hemodynamic response to alter therapy is beneficial to the patients. 3,9 Thus, HVPG measurements remain little used in the care of patients with liver disease.…”

Sendai Virus-Mediated Gene Delivery into Hepatocytes via Isolated Hepatic Perfusion

“…We used a portal pressure of 12 mmHg or less, because greater pressure has been defined as clinically significant portal hypertension. 29) We expected that the sinusoids might alter their sieve structure reversibly within this physiological range, allowing the Sendai virus particles to pass through the sieve. Administration under the controlled high pressure is also a key factor in hydrodynamic-based transfection of plasmid DNA through peripheral vein infusion.…”

Prognostic Markers in Patients with Cirrhosis and Portal Hypertension Who Have Not Bled

“…Hemodynamic response is also associated with a lower incidence of other complications of portal hypertension such as ascites, spontaneous bacterial peritonitis and hepatorenal syndrome, and with increased survival [15][16][17]. However, recent studies suggest that the diagnostic accuracy of hemodynamic monitoring can be improved, mainly in compensated cirrhosis [14,18]. Although the negative predictive value of this technique is very high (around 90%), positive predictive value is modest, especially in primary prophylaxis [19].…”