Guidelines for reliable HVPG measurements have been recently published by hepatologists interested in the procedure [1, 7], but it still lacks widespread standardization across radiology units. A technical summary of the procedure is provided below. Catheterization of the hepatic vein can be carried out under light sedation (Midazolam, up to 0.02 mg/Kg) [8], and is generally well tolerated [9]. Higher doses of midazolam or deep sedation significantly alter pressure measurements [10].

Measuring the HVPG is a safe procedure. Major complications are infrequent and include local injury at the puncture site (femoral, jugular, or antecubital veins) such as bleeding, hematoma, and—more rarely—arteriovenous fistulae or Horner syndrome (in the case of jugular puncture). Ultrasonographic guidance should always be used when available, as it considerably reduces the risk of complications of the procedure. Passage of the catheter through the right atrium might cause supraventricular arrhythmias (most commonly ectopic beats), but in the authors’ experience these are self-limited in over 90 % of cases.

In addition to pressure measurements, other procedures can also be carried out during hepatic vein catheterization. These include: hepatic blood flow (using indicator dilution techniques), TJLB (discussed below), and retrograde CO₂ portography. Right heart catheterization can be performed through the same venous access and prolongs the procedure by only 5 min, with a minimal incremental risk. Right heart catheterization allows the measurement of pulmonary artery pressure, pulmonary wedge pressure, and cardiac output, which can be very useful in the investigation of cardiopulmonary complications of cirrhosis and for pre-transplant evaluation.

The use of the HVPG for the measurement of portal pressure is “as close as we have come to a validated surrogate outcome measure in hepatology” [11]. This is based on consistent observational data showing that improvements in the HVPG (either medication induced or related to treatment of the underlying cirrhosis etiology, e.g., abstinence from alcohol) are associated with improvements in clinical outcomes.

The HVPG is a strong and independent predictor of outcomes in both compensated and decompensated cirrhosis. Cross-sectional studies addressing clinical–hemodynamic correlations have shown that an HVPG of ≥ 10 mmHg is necessary for gastroesophageal varices to form [12, 13]. The importance of this HVPG threshold has been confirmed in a large observational study nested in a randomized trial evaluating patients with compensated cirrhosis [13]. An HVPG of ≥ 10 mmHg was associated with an increased risk of developing varices, of hepatic decompensation (40 % at 4 years) [14], and of hepatocellular carcinoma (HCC) on follow-up [15]. As a result of its prognostic utility, the HVPG threshold of ≥ 10 mmHg is termed “clinically significant portal hypertension.” The HVPG is also relevant in patients with decompensated cirrhosis, where it provides information about the risk of death during follow-up [16–18]. In this setting, 16 mmHg is considered the optimum cutoff value [16, 19, 20]. In the setting of acute variceal hemorrhage, an HVPG of > 20 mmHg is an independent predictor of rebleeding and of mortality [21–23]. On the basis of these clinical–hemodynamic links, recent guidelines support that the HVPG should be used to risk stratify patients, particularly in the research setting [24, 25]. For example, trials evaluating therapies for the prevention of varices should ideally focus on patients with a baseline HVPG of ≥ 10 mmHg. Moreover, it has been suggested that trials evaluating pharmacological therapy for primary and secondary prophylaxis should ideally include HVPG measurements [26], though this can be logistically challenging. In our view, in trials of secondary prophylaxis, in which the rate of events is high, there is no need to use surrogate endpoints such as HVPG measurements. In trials targeting patients with early chronic liver disease , in which the rate of events is very low, HVPG could be used as a surrogate of efficacy.

In compensated cirrhotic patients [15], it has been reported that the HVPG, together with assessment of albumin levels and viral etiology, is an independent predictor of the risk of developing HCC. This risk was six times higher in patients with clinically significant portal hypertension (HVPG ≥ 10 mmHg) than in cirrhotic patients with HVPG values of less than 10 mmHg. The HVPG also plays an important role in the HCC treatment algorithm [27]. In patients with well-compensated cirrhosis and resectable HCC, the presence of clinically significant portal hypertension markedly increases the risk of unresolved hepatic decompensation occurring within 3 months of hepatic resection [28, 29]. Surgical resection for HCC should therefore be restricted to patients without clinically significant portal hypertension [30, 31].

The HVPG has utility in the setting of chronic viral hepatitis. By assessing the liver as a whole, including the potential functional changes in the hepatic microvasculature, it has the potential to provide supplemental information to histology [32]. The correlation of the HVPG with histological fibrosis has been established in both hepatitis B virus-related [33] and hepatitis C virus-related chronic hepatitis [5]. From this data, the majority of patients with significant fibrosis (≥ F2; according to the METAVIR scoring system) have an HVPG over 5 mmHg [33]. Antiviral therapy-related changes in the HVPG are a good way to evaluate disease progression and regression in cases of advanced chronic hepatitis C . Several studies have compared HVPG measurements in patients with chronic hepatitis C taken before and after antiviral therapy. These studies have shown a significant HVPG reduction in patients with advanced stage F3 and F4 after treatment for chronic hepatitis C, particularly in the presence of a sustained viral response [34, 35]. In compensated cirrhotic patients without obvious clinically significant portal hypertension (e.g., without esophageal varices), the HVPG is useful to predict the response to antiviral therapy. In one study, a HVPG cutoff of ≥ 10 mmHg was an independent predictor of response to combination pegylated interferon and ribavirin therapy (sustained virological response of 14 versus 51 % in those with HVPG < 10 mm Hg). The development of thrombocytopenia was also more pronounced in patients with the higher HVPG [36]. Although very promising as a tool to select patients for antiviral therapy, with the advent of novel Hepatitis C therapies , the predictive power of an HVPG of ≥ 10 mmHg will require reevaluation [37].

Variceal bleeding and ascites occur when HVPG values reach at least 12 mmHg [12, 38]. Longitudinal studies have demonstrated that if the HVPG falls below 12 mmHg, either by drug therapy [39, 40] or spontaneously (owing to an improvement in liver disease), [17] variceal bleeding is prevented and varices decrease in size. However, even if this target is not achieved, a decrease in HVPG of at least 20 % [40] from baseline levels offers almost total protection from variceal bleeding in the long term. In patients surviving a bleeding episode, achievement of these targets (reduction below 12 mmHg or more than 20 % from baseline) constitutes the strongest independent predictor of protection from subsequent variceal bleeding, reduces the risk of other portal hypertension-related complications (e.g., ascites, spontaneous bacterial peritonitits), and is associated with an improved survival [41–43]. Interestingly, this survival benefit has not been attributed to an improvement in liver function [44]. These studies are of enormous conceptual importance, as they indicate that the overall prognosis in patients with cirrhosis who survive a variceal bleeding episode can be improved by decreasing portal pressure. The HVPG threshold of 12 mmHg is less precise for predicting bleeding from fundal gastric varices, and occasionally bleeding may occur below this threshold [45].

The clinical application of the prognostic value of changes in HVPG is hampered by the need for repeated measurements of HVPG, and by the fact that a significant number of patients might bleed before a second HVPG measurement is performed [46]. Two studies have shown that evaluation of the acute HVPG response to intravenous propranolol therapy is a useful tool in predicting the efficacy of nonselective beta-blockers in preventing first bleeding or rebleeding [47, 48]. The acute HVPG response to propranolol was independently associated with survival in these patients [49]. It is important to note that the threshold decrease in HVPG that defines a good response (associated with decreased bleeding and mortality) in these studies was a fall of 10–12 % from baseline (instead of the 20 % decrease that applies when using the chronic response).

A relevant question is whether there is any benefit in monitoring pharmacological therapy for portal hypertension in day-to-day practice. It is important to note that the benefits of beta-blockers in preventing first bleeding and rebleeding were demonstrated in trials in which treatment was not HVPG guided, that is, beta-blockers were given empirically, either without assessing HVPG response or if assessed, not taking into account to guide therapy [50]. To date, an HVPG-guided treatment strategy has not yet been associated with improved clinical outcomes [51, 52], in large part related to the fact that it remains unclear what therapy to offer to nonresponders [46, 51]. Given the invasive nature of the HVPG measurement and the lack of standardization across centers, until further data is available, HVPG-guided therapy is likely to remain limited to the setting of clinical research.

Another important issue is whether the classification of a person as a hemodynamic responder can be maintained over the long term [53]. To evaluate this, 40 hemodynamic responders (in the setting of secondary prophylaxis) were followed with annual HVPG measurements for a mean follow-up period of 48 months. Although all abstinent alcoholic patients retained hemodynamic responsiveness, only 36 % of non-abstinent alcoholics and 50 % of patients with viral cirrhosis did so. The loss of hemodynamic response was associated with an increased risk of rebleeding, death, and liver transplantation.

The first step in the assessment of a potential new agent for treating portal hypertension should involve testing its capacity to modify portal pressure (evaluated as HVPG). It should be noted, however, that the demonstration of a portal hypertensive effect for a new drug might not translate into objective clinical benefit. The association between pharmacological reduction in portal pressure and improved outcomes has been consistently demonstrated so far only for beta-blocker-based therapies. Further validation of the accuracy of the HVPG response as a surrogate with new drug classes (other than beta-blockers) is desirable.

TJLB is generally performed after HVPG measurements, and only adds 10–15 min to the procedure. TJLB was first described in humans by Weiner (7) and Rosch (8). This technique avoids crossing of the liver capsule by accessing the liver parenchyma via the hepatic vein or IVC, therefore significantly decreasing the risk of bleeding. Table 7.1 shows the main circumstances in which a transjugular approach is preferred over a percutaneous approach [54–56]. Main contraindications for the procedure are summarized in Table 7.2.