Hepatic Venous Pressure Gradient

Abbreviations

HCC

hepatocellular carcinoma

HVPG

hepatic venous pressure gradient

IVC

inferior vena cava

TIPS

transjugular intrahepatic portosystemic shunt

WHVP

wedged hepatic venous pressure

Portal hypertension is defined as high blood pressure in the splanchnic venous system and is most commonly seen in the setting of long‐standing liver disease. The consequences of portal hypertension can be life‐threatening and include acute bleeding from gastroesophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Given these debilitating complications, defining the severity of portal hypertension is critical for the management and prognosis of patients with cirrhosis. ¹

Although portal hypertension can be inferred from the patient's history of cirrhosis, clinical manifestations, and noninvasive imaging, hepatic venous pressure gradient (HVPG) measurements remain the gold standard for diagnosis. Furthermore, if uncertainty exists in patients without a history of cirrhosis or preexisting risk factors, HVPG can confirm the diagnosis. ²

Diagnosis of Portal Hypertension by Portal Venous Pressure Gradient Measurement

In chronic liver disease, an increase in sinusoidal resistance to blood flow results in elevated portal pressures. ³ HVPG is a quantification of this resistance achieved through a minimally invasive fluoroscopy‐guided procedure.

As opposed to direct and more invasive portal venous sampling, HVPG is the calculated difference between a wedged and a free venous pressure, measured with a catheter positioned in the hepatic vein (Fig. 1). Wedged hepatic venous pressure (WHVP) is an estimate of pressure within the portal venous system, whereas free hepatic venous pressure reflects systemic venous pressure. ⁴ , ⁵ A HVPG ≤ 5 mm Hg is normal, whereas a gradient >5 mm Hg is diagnostic for portal hypertension. ⁴ Of note, WHVP may be normal or only slightly elevated in patients with noncirrhotic causes of portal hypertension, resulting in a normal gradient despite severe portal hypertension. ⁶

FIG 1.

HVPG is the difference between the wedged hepatic pressure and free hepatic pressure.

Procedural Technique

HVPG measurements are performed under ultrasound and fluoroscopic guidance. The right internal jugular vein is commonly chosen because it provides direct continuity with the superior vena cava, right atrium, and inferior vena cava (IVC). Other peripheral veins can also be accessed, such as left internal jugular, external jugular, or femoral or brachial veins. A vascular sheath is then advanced into the IVC. Through the sheath, a catheter is used to select the right hepatic vein. A free hepatic pressure measurement is obtained with the catheter in this position. The wedged pressure can be determined via several techniques, such as advancing the catheter until there is no venous reflux or washout during contrast injection or, more commonly, via balloon catheter occlusion (Fig. 2). Measurements are obtained at least three times to assure that the values are reproducible, from which the average is reported. IVC and right atrial pressures are also typically obtained prior to catheter removal. Often the procedure is performed concurrently with transjugular core biopsy of the liver. ⁷

FIG 2.

(A) Hepatic venogram prior to free hepatic pressure measurements shows contrast opacifying the entirety of the right hepatic vein and refluxing back to the IVC (red arrow). (B) Hepatic venogram obtained with balloon occlusion preventing reflux into the IVC prior to obtaining wedged hepatic pressure measurements (blue arrow). (C) Illustration showing balloon occlusion of the hepatic vein to obtain WHVP.

Role of HVPG in Determining Prognosis of the Patient With Cirrhosis

While a biopsy sample represents only a small liver area, serial HVPG measurements characterize the overall degree of fibrosis or cirrhosis reflecting an underlying heterogeneous disease process. ⁸ Although similar, less invasive surveillance options such as elastography should be considered, repeat HVPG measurements over months to years can help monitor disease progression over time. ⁹

The severity of cirrhosis is often described as a spectrum from asymptomatic, compensated disease to severely decompensated cirrhosis with symptoms of hepatic encephalopathy, variceal hemorrhage, and ascites. ¹⁰

An HVPG > 5 mm Hg signifies sinusoidal portal hypertension in compensated cirrhosis. HVPG values ≥10 mm Hg represent clinically significant portal hypertension that is predictive of decompensation and the development of symptoms. ⁴ , ¹⁰

Improvement in fibrosis has been shown in patients who have lower pretreatment HVPGs when obtained before the initiation of medical management. Therefore, screening for compensated disease with HVPG measurements can prompt the early start of medical management with nonselective beta‐blockers. ¹¹ Fewer portal hypertension‐related complications have been reported in patients with improvements in HVPG to <12 mm Hg or a decrease in HVPG more than 20% from pretreatment baseline. ¹² Prognostic thresholds for HVPG values are listed in Table 1.

TABLE 1.

HVPG Thresholds With Prognostic Significance in Patients With Cirrhosis

HVPG Thresholds (mm Hg)	Prognostic Significance
≤5	Normal or noncirrhotic portal hypertension
>5	Portal hypertension
>10	Clinically significant portal hypertension that is predictive of decompensation
>12	Variceal hemorrhage
>16	Variceal rebleeding
>20	Failure to control active hemorrhage, high mortality
>30	Spontaneous bacterial peritonitis

Variceal Hemorrhage

Variceal hemorrhage is a significant cause of death in patients with portal hypertension. HVPG measurements are useful in determining the risk for development of varices related to advanced cirrhosis and the likelihood that the varices will bleed if present. Values ≥10 mm Hg are predictive of variceal formation. Once varices evolve, reliable HVPG target values can be achieved to decrease the risk for first or recurrent hemorrhage. For example, bleeding is unlikely when the gradient is ≤12 mm Hg. ¹³

In cases of active bleeding, HVPG measurements can be beneficial for prognosis and treatment planning, including determining the dose of somatostatin and guiding the placement of a transjugular intrahepatic portosystemic shunt (TIPS). ¹⁴ , ¹⁵ Once variceal bleeding has occurred, an HVPG ≥ 20 mm Hg is predictive of early rebleeding and death. ¹⁶

Response to Medical Management

Primary prevention of variceal bleeding with pharmacological therapy, most commonly beta‐blockers and statins, has been associated with reduction in HVPGs over time. ¹⁷ , ¹⁸ Adequate hemodynamic improvement with chronic beta‐blocker administration is defined as a reduction in HVPG to ≤12 mm Hg or a decrease of at least 10% to 20% from the patient's baseline value. ¹⁹ Despite this association, the use of HVPG measurements to evaluate treatment response has been criticized because of variability in data and lack of feasibility. Two invasive interventions must be performed several weeks apart resulting in unnecessary procedural risk and medical costs. ²⁰

Prognostic Role in Patients With Cirrhosis WHO are Undergoing Surgery

Patients with cirrhosis remain a high‐risk surgical population with increased postsurgical mortality rates. Among other inherent risks of cirrhosis, portal hypertension is associated with increased bleeding and challenges with hemodynamic management, predisposing these patients to multisystemic complications. HVPG in patients with cirrhosis who are undergoing elective extrahepatic surgery can be prognostic. An HVPG ≥ 16 mm Hg is associated with increased mortality, whereas a cutoff of HVPG ≥ 20 mm Hg identifies a very high‐risk population. This evaluation is specifically relevant to patients who lack traditional clinical markers for portal hypertension but are still found to have elevated HVPGs. ²¹

Hepatocellular Carcinoma and Surgical Resection

Elevated HVPG is an independent risk factor for the development of hepatocellular carcinoma (HCC) regardless of the severity of cirrhosis. ⁴ In the setting of diagnosed HCC, HVPG measurements assist in identifying patients who are candidates for surgical resection or liver transplantation. Because resistance to blood flow increases following partial hepatectomy, elevated baseline preoperative HVPG can predict hepatic decompensation and poor long‐term outcomes in patients with cirrhosis after liver resection for HCC. Elevated HVPG has been significantly associated with unresolved decompensation within 3 months after surgery. ²²

TIPS Placement

Venous pressure gradients can be used not only as a diagnostic tool but also in treating portal hypertension, specifically when placing a TIPS. In patients with portal hypertension, a TIPS is commonly created to treat acute variceal hemorrhage or chronic refractory ascites that require multiple paracenteses. TIPS creation reduces portal pressures by establishing a channel from a hepatic vein to an intrahepatic portal vein. This channel is achieved by deploying a stent across the liver parenchyma that allows for portal venous blood to bypass the damaged liver and to return to systemic circulation via the hepatic vein. TIPS placement results in immediate decompression of portal hypertension and is most effective in patients with an HVPG ≥ 20 mm Hg.

After TIPS placement, direct pressure measurements can be obtained from the right atrium and the portal vein to determine the new portosystemic gradient. A gradient <12 mm Hg or 50% reduction from the initial gradient ensures adequate decrease in portal pressure. ²³ During the procedure, TIPS diameter can be adjusted in real time to achieve an optimum portosystemic gradient. Furthermore, pressure measurements can guide troubleshooting with subsequent TIPS revisions. ²⁴

Complications

Despite being a relatively safe, reproducible, and quick procedure (often less than 30 minutes for completion), obtaining HVPG measurements is an invasive technique usually offered only at large hospital centers. Procedural complications are typically minor, including cardiac arrhythmias from guidewire access via the right heart, pain at the access site, and vagal reaction. Other procedural risks, such as bleeding and infection, are exceedingly rare. No deaths have been reported. ⁴