Advances in portal pressure measurement: Endoscopic techniques, challenges, and implications for liver transplantation

Abstract

Portal hypertension is a critical determinant of prognosis in chronic liver disease and a key factor in evaluating candidates for liver transplantation. Traditional methods such as hepatic venous pressure gradient (HVPG) measurement have long been considered the gold standard for assessing portal pressure. However, these methods are invasive and carry procedural limitations. Recent advances in endoscopic ultrasound (EUS)-guided techniques have emerged as promising alternatives, offering direct and minimally invasive assessment of portal pressure. EUS-guided portal pressure gradient measurement enables real-time evaluation of haemodynamic through direct access to the portal system. This technique has shown to be as accurate as HVPG, and it has some extra benefits, like the ability to take liver biopsies and check collateral circulation all at the same time. Despite these benefits, the technique poses challenges such as operator dependence, procedural complexity, and limited standardization across centres. This minireview highlights the evolution of portal pressure measurement, focusing on the potential of EUS-guided techniques in pre-transplant assessment, risk stratification, and monitoring therapeutic outcomes. Furthermore, it discusses the technical challenges, clinical implications, and future directions for integrating these innovations into routine practice. Advances in portal pressure measurement hold significant promise for enhancing decision-making and outcomes in liver transplantation.

Key Words: Portal hypertension; Hepatic venous pressure gradient; Endoscopic ultrasound; Portal pressure gradient; Liver transplant; Liver cirrhosis; Portal pressure measurement

Core Tip: The accurate measurement of portal hypertension (PH) is crucial in assessment of patients with liver cirrhosis as it significantly impacts the disease progression and prognosis. Moreover, it plays a critical role in guiding surgical decisions especially liver transplant. Hepatic vein pressure gradient is considered gold standard technique for measuring PH but is not widely used due to various factors like lack of availability, technical expertise, risk of contrast and ionizing radiation and inaccuracy in pre-sinusoidal causes of PH. Endoscopic ultrasound (EUS) has emerged as a safe and reliable method for portal pressure measurement. The portal pressure gradient (PPG) can be estimated as a single procedure while evaluating for collaterals including oesophageal and gastric varices or while doing a liver biopsy. With increase in cases of liver transplant in future, EUS guided PPG might play a crucial role in peri-operative and post-operative management of such patients.

INTRODUCTION

Portal hypertension (PH) refers to an elevated blood pressure within the portal venous system, often resulting from increased resistance to blood flow through the liver, as seen in cirrhosis and other liver diseases that cause hepatic fibrosis. The pathophysiology of PH is driven by several factors, including heightened intra-hepatic vascular resistance and increased splanchnic blood flow[1,2].

Accurate measurement of portal pressure is crucial in assessing patients with liver cirrhosis, as PH significantly impacts both prognosis and the progression of the disease. It is the primary cause of the development of collateral circulation and the onset of hyperdynamic circulatory syndrome, which can lead to complications such as oesophageal varices (EV), gastrointestinal bleeding, ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy[3].

Portal pressure measurement is currently the most reliable method for evaluating the effectiveness of therapies aimed at managing PH, including pharmacological treatments, surgical interventions, and interventional radiology. Moreover, it plays a key role in guiding surgical decisions, especially during liver transplantation. In cases with markedly elevated portal pressure, the risk of complications, such as bleeding during surgery, increases. Additionally, portal hyper-perfusion that exceeds the graft's capacity can lead to small-for-size syndrome, which is characterized by ascites, cholestasis, and coagulopathy. Accurate measurement of portal pressure helps the surgical team anticipate these challenges and take appropriate precautions, which may include the need for inflow modulation[4].

This mini-review aims to provide an overview of recent developments in portal pressure measurement, particularly through endoscopic techniques, and to examine the associated challenges and their implications for liver transplantation outcomes.

CLASSIFICATION OF PH

PH is categorized into pre-hepatic, hepatic, and post-hepatic types, based on the location of increased vascular resistance. Pre-hepatic causes include conditions like extra-hepatic portal venous obstruction, portal vein (PV) thrombosis, and PV obstruction, which result from tumors or inflammation that infiltrate or extend to the PV. Hepatic causes are further divided depending on their relation to the sinusoids. Pre-sinusoidal causes include conditions such as adult polycystic disease, congenital hepatic fibrosis, cholestatic liver disease, schistosomiasis, sarcoidosis, and idiopathic PH/non-cirrhotic portal fibrosis (NCPF). Sinusoidal causes, which account for approximately 80% of all PH cases, include alcoholic liver cirrhosis, non-alcoholic fatty liver disease, and viral hepatitis. Post-sinusoidal causes include sinusoidal obstruction syndrome and Budd-Chiari syndrome. Post-hepatic causes, such as right heart failure or constrictive pericarditis, are generally secondary to liver congestion[5].

These different causes can be distinguished using the hepatic venous pressure gradient (HVPG), measured via hepatic venography. HVPG is calculated by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP), i.e., (HVPG = WHVP - FHVP). In patients with pre-hepatic and pre-sinusoidal conditions, HVPG remains normal because the sinusoidal pressure is unaffected, leading to a discrepancy between the HVPG and the actual PV pressure. In patients with sinusoidal and post-sinusoidal diseases, HVPG is elevated due to increased intra-sinusoidal pressure, which closely mirrors the actual PV pressure. In cases of post-hepatic disease, both wedged and FHVPs are elevated, but the HVPG remains normal (Table 1)[5,6].

Table 1 Classification of portal hypertension and differences in pressure measurement.

Classification type	Definition	Etiology	Location of obstruction/resistance	Key characteristics	Pressure measurement differences
Prehepatic PH	Increased pressure in the portal venous system before it enters the liver	PV thrombosis, splenic vein thrombosis	PV, splenic vein	PV obstruction before liver: Minimal liver damage	FHVP: Normal, WHVP: Normal, HVPG: Normal
Intrahepatic presinusoidal PH	Increased resistance before liver sinusoids due to portal venous inflammation	Portal fibrosis, early cirrhosis, granulomatous diseases	PV, periportal space, and small vessels	Early stage of cirrhosis or hepatic fibrosis: Less severe than sinusoidal or post-sinusoidal	FHVP: Normal, WHVP: Normal/high, HVPG: Normal/high
Intrahepatic sinusoidal PH	Increased resistance in the liver sinusoids due to sinusoidal injury	Alcoholic liver disease, viral hepatitis, cirrhosis, metabolic dysfunction-associated steatohepatitis	Liver sinusoids and hepatic microcirculation	Significant increase in intrahepatic resistance: Due to severe sinusoidal damage	FHVP: Normal, WHVP: High, HVPG: High
Intrahepatic post-sinusoidal PH	Increased resistance beyond the sinusoids due to changes in venous outflow	Veno-occlusive disease, granulomatous phlebitis	Hepatic venules, post-sinusoidal vessels	Obstruction of hepatic venules and post-sinusoidal spaces: Less common than sinusoidal	FHVP: Normal, WHVP: High, HVPG: High
Post-hepatic PH	Increased pressure after the liver due to obstruction in the venous outflow	Budd-Chiari syndrome, right-sided heart failure, constrictive pericarditis	Hepatic veins, inferior vena cava	Obstruction after liver affects venous outflow: Liver often preserved in function	FHVP: High, WHVP: High, HVPG: Normal/high

FHVP: Free hepatic venous pressure; HVPG: Hepatic venous pressure gradient; PH: Portal hypertension; PV: Portal vein; WHVP: Wedged hepatic venous pressure.

CLINICALLY-SIGNIFICANT PH

An increase in portal pressure is considered clinically significant PH (CSPH) when it reaches a porto-hepatic gradient of ≥ 10 mmHg. This threshold is associated with the onset of complications such as EV and ascites. However, simply determining the presence or absence of CSPH is not enough when evaluating PH. The degree of portal pressure plays a critical role in assessing risk, with higher levels of pressure linked to progressively worse outcomes. A portal pressure greater than 10 mmHg is associated with an increased risk of EV, ascites, and decompensation after surgery for patients with hepatocellular carcinoma (HCC), while a pressure ≥ 12 mmHg is linked to a higher risk of variceal bleeding. A pressure exceeding 16 mmHg has been correlated with survival outcomes, the onset of clinical decompensation in patients with varices, and a higher risk of oesophageal re-bleeding and mortality in patients with decompensated cirrhosis. Pressures above 20 mmHg are associated with difficulty controlling variceal bleeding and higher mortality rates, while levels greater than 22 mmHg are linked to mortality in patients with alcoholic cirrhosis and acute alcoholic hepatitis[7].

Conversely, a reduction in portal pressure is associated with improved prognosis. Specifically, achieving a portal pressure below 12 mmHg, or reducing it by at least 20% from baseline, is necessary to achieve clinical efficacy in the treatment of PH[8]. Therefore, in patients with liver cirrhosis, it is essential not only to assess whether CSPH is present, but also to quantify the degree of PH and monitor changes in portal pressure over time[9].

CONVENTIONAL METHODS FOR ASSESSING PH

There are certain minimally invasive techniques to assess PH including ultrasonography (USG), elastography and upper gastrointestinal endoscopy though HVPG remains the gold standard. USG is undoubtedly the first-line imaging technique for patients with suspected PH due to its non-invasive nature, low cost and easy availability. The presence of porto-systemic collaterals and the reversal of PV blood flow are suggestive of CSPH with specificity reaching near 100%. The presence of enlarged spleen is one of the most sensitive USG sign, but with limited specificity[10-12]. Contrast enhanced USG has definite role in suspected thrombus of the portal venous system[13]. Reduced PV velocity, a sign of PH, is an important quantitative parameter with prognostic significance[10]. Besides this, USG provides an comprehensive assessment of liver including liver echotexture, surface pattern, presence of regenerative or dysplastic nodules and ascites[11].

Elastography is another non-invasive technique to detect CSPH which has gained popularity recently. It can be carried out using USG, fibroscan device or magnetic resonance imaging[14,15]. A systematic review and meta-analysis including 9 studies and 746 patients found good utility of shear wave elastography (SWE) in detecting CSPH with 85% sensitivity and 85% specificity[16]. A prospective observational study by Lucchina et al[17] on role of spleen stiffness in predicting PH found lower accuracy of spleen stiffness in predicting EV as compared to liver stiffness. Another systematic review and meta-analysis with 26 studies and 4337 patients found good correlation of transient elastography (TE) with HVPG and liver stiffness[18]. While liver stiffness measurement (LSM) of ≥ 15 kPa is suggestive of CSPH, LSM ≥ 25 kPa can definitely rule in CSPH[19] The limitations of TE using a fibroscan device is related to its high cost, non-feasibility in patients with ascites and unreliable measurement in patients with high body mass index and elevated aminotransferase levels[19]. SWE has similar advantages and limitations of TE except for the fact that its more readily available although the cutoffs for SWE are not well validated[20].

There is definite role of upper gastrointestinal endoscopy in detecting the presence of CSPH. The presence of gastro-oesophageal varices is a surrogate marker for CSPH. AASLD suggests using upper gastrointestinal endoscopy as a screening tool to detect CSPH when TE is not available[19].

HVPG MEASUREMENT AS A GOLD STANDARD

In liver cirrhosis, where the communication within the sinusoids is disrupted, the HVPG closely approximates the portal pressure. As a result, HVPG measurement is considered the gold standard for assessing PH, both in research and clinical practice. A normal HVPG is ≤ 5 mmHg, while values exceeding 5 mmHg are diagnostic of PH. CSPH is diagnosed when the HVPG is ≥ 10 mmHg, and this level is associated with an increased risk of clinical decompensation, including complications such as ascites, variceal bleeding, hepatic encephalopathy, and HCC. The likelihood of variceal rupture rises when the HVPG reaches ≥ 12 mmHg. An HVPG of ≥ 16 mmHg is linked to a higher risk of mortality, while a value of ≥ 20 mmHg is associated with an increased risk of treatment failure for variceal bleeding and higher mortality[8,21].

HVPG measurement can be conducted using various approaches, including the trans-jugular, transfemoral, or peripheral ante-cubital vein method. In clinical practice, HVPG measurements are often performed concurrently with other invasive procedures, such as trans-jugular liver biopsy, trans-jugular intra-hepatic porto-systemic shunt (TIPS), or balloon-occluded retrograde trans-venous obliteration. Given the somewhat invasive nature of HVPG measurement, patient tolerance is an important consideration. Studies have shown that procedures lasting less than 35 minutes are well tolerated by more than 80% of patients (Figure 1)[22]. The median of three readings is taken as HVPG. FHVP is measured by positioning the pressure- sensitive catheter at the distal portion of hepatic vein (HV) without occluding flow, while WHVP is measured by occluding blood flow by inflating the balloon catheter, thus providing a standing column to the PV via the hepatic sinusoid[23].

Figure 1 Technique of doing hepatic venous pressure gradient measurement. Hepatic vein (HV) pressure gradient measurement can be conducted using various approaches, including the trans-jugular, transfemoral, or peripheral antecubital vein method. Free HV pressure is measured by positioning the pressure-sensitive catheter at the distal portion of HV without occluding flow, while wedged HV pressure is measured by occluding blood flow by inflating the balloon catheter, thus providing a standing column to the portal via the hepatic sinusoid. HV pressure gradient measurement = wedged HV pressure - free HV pressure.

A study by Yamamoto et al[23] involving 41 patients demonstrated that HVPG measurement using the peripheral ante-cubital veins had a median procedure time of 19.1 minutes and was deemed safe in 98% of cases, without serious complications such as significant hematoma or nerve injury. Additionally, HVPG serves as a prognostic marker, allowing for objective evaluation of the efficacy of treatments like nonselective beta-blockers or TIPS in managing PH[24]. While HVPG remains essential for assessment, efforts to reduce its invasiveness should be prioritized. There are several challenges associated with the measurement of HVPG.

Heterogeneity/variation of HVPG

A study by Keiding and Vilstrup[25] measured HVPG in two separate HVs in 102 cirrhotic patients and 27 controls (patients without liver disease). They found variability between measurements taken from the first and second HVs, with this difference being more pronounced in patients with cirrhosis compared to the controls. Additionally, over 60% of the patients exhibited HVPG values with a wide range, spanning from 4 mmHg to 34 mmHg. Although some of these differences may be due to physiological variations, the significant variability in HVPG measurements highlights the importance of exercising caution. Additionally, inter-observer variability is a concern. Furthermore, the use of deep sedation with propofol and remifentanil can amplify HVPG variations, making it an important limitation to consider during hepatic venous catheterization.

Presence of veno-venous communication

Hepatic veno-venous communication is the connection between different HVs. The WHVP does not reflect portal pressure in patients with hepatic veno-venous communications. This is logically acceptable because the presence of veno-venous communication has a suppressive effect on the actual pressure.

Complications

Minor problems can happen during or after hepatic venous catheterization. These include pain at the puncture site (cervical or femoral), vagal reaction, and short-term arrhythmia from the guidewire moving. In addition, care should be taken against the allergy and/or adverse events caused by iodinated contrast material as contrast enhancement is necessary to ensure complete occlusion by balloon inflation in the HV and to evaluate the vascular/sinusoidal appearance.

The recent Baveno VII consensus has recommended incorporating elastography indices, such as LSM and spleen stiffness measurement, along with non-invasive tests like serum biomarkers and combined scoring systems in managing PH (Table 2)[1,26-28]. However, HVPG continues to be recognized as the gold standard in clinical practice.

Table 2 Non-invasive imaging modalities for assessment of clinically significant portal hypertension.

Imaging modality	Description	Sensitivity (%)	Specificity	Limitations
Ultrasound elastography (liver stiffness measurement)	Uses shear wave elastography or transient elastography to assess liver stiffness, which correlates with portal pressure	0.81 (0.73–0.87)	0.83 (0.77–0.88)	May be less accurate in obese patients or those with ascites. Affected by liver inflammation and cholestasis
Spleen stiffness measurement	Measures spleen stiffness to estimate portal pressure and PH severity. Reflects not only increased intrahepatic vascular resistance but also splenic haemodynamic and fibrosis	0.85 (0.69–0.93)	0.86 (0.74–0.93)	A dedicated device is required. Difficult to measure without splenomegaly
Magnetic resonance elastography	Uses MRI technology to assess liver stiffness, capable of covering the whole liver	80-90	90-95	High cost, limited availability
Doppler ultrasound	Measures the velocity of blood flow in the PV and hepatic veins, used to infer PH	70-90	70-90	Operator-dependent, limited by technical factors (e.g., patient positioning)
Computed tomography or MRI-based imaging (with contrast)	Involves imaging of the PV, spleen, and liver, providing visual signs of PH, such as varices or splenomegaly	70-90	75-90	Limited sensitivity in detecting mild PH, expensive

MRI: Magnetic resonance imaging; PH: Portal hypertension; PV: Portal vein.

ENDOSCOPIC ULTRASOUND FOR PORTAL PRESSURE MEASUREMENT

Endoscopic ultrasound (EUS) is an ideal technique to gain access to the PV owing to its close proximity to gastrointestinal tract. EUS guided PV access has numerous clinical implications including PV angiography, measurement of the portal pressure, possible creation of porto-systemic shunt similar to TIPS and PV sampling for early detection of gastrointestinal cancer[29]. This section focuses on the historical aspects of portal pressure measurement and outlines the principals involved, technical aspects and tools employed in this technique.

Animal studies

A series of research in animal model from year 2004 to 2017 paved the way for this innovative new technique in the field of endo-hepatology. The study by Lai et al[30] and Giday et al[31] not only demonstrated the feasibility of EUS guided PV catheterization in animal model, but also good correlation between portal pressure measurement using the EUS and the trans-hepatic route. Huang et al[32] were the first to demonstrate the use of compact manometer (CM) for PV pressure measurement and the fact that there was good correlation between EUS-portal pressure gradient (PPG) and standard trans-jugular technique. Schulman et al[33,34] demonstrated the novel technique of measuring EUS portal pressure using a digital pressure wire which can be passed through the 22G needle with real time remote display.

Human studies

Fujii-Lau et al[35] successfully performed the first case of EUS guided PV pressure measurement using a 22G needle in a patient with suspected PH having arteriovenous malformations. The first prospective pilot study was done on twenty-eight patients with suspected PH by Huang et al[36] in 2017. They demonstrated feasibility and safety of measuring PPG using 25G needle and a CM similar to the one used in the same group’s animal study. This study and subsequent studies showed good correlation of portal pressure measurements with clinical and endoscopic parameters[37-39]. A multi-center retrospective study across eight centers involving 385 patients demonstrated a 97% technical success rate for EUS-PPG. Higher median PPGs were observed in patients with EV (11.6 mmHg vs 4.1 mmHg), portal hypertensive gastropathy (10.5 mmHg vs 3.3 mmHg), and thrombocytopenia (7.6 mmHg vs 4.4 mmHg). EUS-PPG was the strongest predictor of biopsy-proven cirrhosis, outperforming non-invasive markers like fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio. EUS-PPG measurements showed strong correlations with clinical signs of PH and liver histology findings. Patients with higher PPG readings were significantly more likely to have cirrhosis confirmed on biopsy[40].

Technique and challenges

Esophagogastroduodenoscopy (EGD) is the first preferred investigation to rule out presence of oesophageal or gastric varices. EUS is then done to find the optimal site for PV and HV puncture through the trans-gastric route. The HV is usually punctured first followed by the PV. Middle HV and umbilicated portion of the left PV are the preferred site of puncture respectively due to larger calibre and better alignment[39]. The safety of both 22G fine needle aspiration (FNA) needle[35,37,39] and 25G needle[36,38,41] for puncture has been established in various animal and human studies done so far. The measurement of PPG requires non-compressible tubing and a portable CM (EchoTip Insight, Cook Medical, Winston-Salem, NC, United States) besides an echoendoscope and needle. In the absence of the CM, conventional electrocardiographic monitor with central venous pressure module connected via a pressure transducer can be used to measure PPG[37,39,42]. The FNA needle is attached to the non-compressible tubing which is then attached to either CM or the conventional electro-cardiogram monitor depending upon availability. The presence of air bubbles in the non-compressible tubing can cause false reading and should be taken care of (Figure 2).

Figure 2 Technique of doing endoscopic ultrasound guided portal pressure gradient measurement. The hepatic vein (HV) is usually punctured first followed by the portal vein (PV). Middle HV and umbilicated portion of the left PV are the preferred site of puncture respectively due to larger calibre and better alignment using a 22G or 25G fine needle aspiration (FNA) needle. The FNA needle is attached to the non-compressible tubing which is then attached to either compact manometer or the conventional electro-cardiogram monitor depending upon availability. With patient in supine position and pressure transducer kept at the level of mid-axillary line, three sequential readings are taken for each vessel for 60 seconds and mean calculated.

After taking the puncture, 1 mL of heparin is flushed through the needle to clear the lumen and confirm the intra-vascular placement. With patient in supine position and pressure transducer kept at the level of mid-axillary line, three sequential readings are taken from each vessel for 60 seconds and mean calculated. While removing the needle, the needle track is observed with colour doppler to exclude any bleed. In case of any doppler flow, needle is kept inside to cause mechanical hemostasis.

The technical success rate of doing EUS-PPG has been found to be ranging from 92% to 100% in studies, suggesting ease of doing the procedure in expert hands[29,36,38,43,44]. A meta-analysis of 8 studies and 178 patients indicated a clinical success rate of 85.4%, defined as a good connection between EUS-PPG findings and liver fibrosis on histology[45]. EUS-PPG ≥ 5 mmHg has been found to predict histological hepatic fibrosis stage ≥ 3 on liver biopsy. The authors also found 13 times increased risk of having cirrhosis in patients having EUS-PPG > 5 mmHg as compared to those having EUS-PPG < 5 mmHg[38].

Contraindications, complications and limitations

The patients selected for EUS-PPG typically have liver cirrhosis, requiring a comprehensive pre-procedure evaluation. The procedure should be avoided if the patient has HCC, massive ascites, international normalized ratio > 1.5, contraindication to EGD, any anatomic anomaly preventing vessel access or the patient is on blood thinning medication in last 5 days[39,43].

The procedure has been found to have high success rate with considerable safety in various animal and human studies done so far. A systematic review and meta-analysis which included four studies and 128 patients reported no serious adverse event like bleeding, perforation or infection[44]. Another recent review and meta-analysis of 8 studies and 178 patients, reported the adverse event rate to be 10.9% with 93.7% patients having mild adverse event like mild abdominal pain, sore throat, etc.[45]. The most common serious adverse event reported is bleeding at the site of vessel puncture leading to liver hematoma, which is usually self-limiting[41]. The experience with animal studies suggests higher risk of hematoma via the trans-duodenal as compared to the trans-gastric route due to the natural mechanical tamponade provided by the liver parenchyma in the latter[30].

There are several drawbacks of doing an EUS-PPG including the invasive nature of procedure, cost, need for technical expertise and anesthesia related complications. There have also been concerns of moderate to deep sedation affecting the PPG measurements. Besides this, there is still lack of sufficient good quality prospective study to prove good correlation between EUS-PPG and HVPG.

The use of EUS-PPG is currently limited by its restricted availability across centers and the technical expertise it demands. The procedure requires proficiency in both EUS imaging and vascular access, skills that many endo-sonographers may lack. There is significant variation in technique including site of PV puncture, needle type and pressure measurement devices. The lack of universally accepted protocols leads to heterogeneity in results across studies. The normal reference ranges and cut-off values for PH based on EUS-PPG are yet to be established. While PPG measurement using electro-cardiogram monitor or CM is feasible, there are still no universally approved devices specially designed for the same.

There is an urgent need for consensus guidelines on patient selection, procedural technique and reporting standards for EUS-PPG. Additionally, multi-centric studies are essential to define normal reference values and cut-offs across populations. Standardizing protocols, including sedation practices, is also crucial to ensure measurements closely reflect awake-state values.

Comparative analysis with traditional HVPG

There are several advantages of doing an EUS-PPG over HVPG: (1) Measures the portal pressure directly; (2) No exposure to ionizing radiation; (3) No intravenous contrast requirement; and (4) Can be used in pre-sinusoidal causes of PH like NCPF, PV thrombosis. The drawbacks of EUS-PPG as compared to HVPG include: (1) Limited experience; (2) Higher cost; (3) Lack of expertise; and (4) Unavailability of standard training.

IMPLICATIONS OF PH ON LIVER TRANSPLANT

PH, a critical factor in the progression of liver disease, plays a key role in determining the eligibility for liver transplantation, predicting peri-operative risks, and guiding post-transplant care. Accurate measurement of portal pressure, typically assessed using the HVPG or other emerging methods, has significant clinical implications throughout the liver transplantation process.

Graft inflow modulation (GIM) is employed to prevent small-for-size syndrome, a complication arising from excessive portal inflow to a relatively small liver graft. Intra-operative portal pressure measurements guides decisions regarding GIM techniques such as splenic artery ligation or splenectomy. For instance, PV pressures exceeding 20 mmHg may prompt the use of inflow modulation strategies to mitigate the risk of small-for-size syndrome[46].

Although EUS-PPG is not directly utilized for intra-operative GIM, its role in preoperative assessment of PH could indirectly inform decisions related to GIM. Further research is needed to establish protocols integrating EUS-PPG measurements into the surgical planning of liver transplantation.

Concept of hepatic artery buffer response

The portal and arterial blood flow to the liver is regulated by local paracrine mechanisms, primarily involving adenosine. Lautt first described this regulatory process called as the hepatic artery buffer response. When portal blood flow increases, hepatic artery flow decreases in response. This occurs because adenosine, a vasodilator, is washed away from the sinusoids, resulting in vasoconstriction and a reduction in arterial flow. However, portal flow does not adjust in the same manner as arterial flow. In PH, not only does portal flow increase, but a reduction in arterial flow is also thought to contribute to graft dysfunction and ischemia, particularly affecting cholangiocytes. After liver transplantation, partial liver grafts receive less hepatic artery flow than full grafts in absolute terms. Following reperfusion, the portal-to-hepatic arterial flow ratio rises from 6.6 in full grafts to 15.4 in partial grafts[47].

Measuring portal blood flow and pressure in the recipient at the beginning of surgery and after reperfusion can help in intra-operative decision-making for inflow modulation. A sudden shift in hemodynamics occurs when a cirrhotic liver is replaced with a donor liver, which has greater pliability, creating a low-resistance pathway that allows a large volume of blood to flow from the splenic vein. The graft liver has higher compliance compared to the cirrhotic liver, meaning that resistance to portal flow is significantly reduced. As a result, the volume of blood passing through each gram of liver tissue increases. This enhanced blood flow through the sinusoids generates shear stress, which is a key factor in stimulating hepatic regeneration. Hepatotrophic growth factors interact with peri-portal hepatocytes, and sinusoidal permeability increases as part of this process. It is crucial for portal flow to remain at an optimal level—too little flow impairs regeneration and graft function, while excessive flow can lead to the well-known small-for-size syndrome[48,49].

Pre-transplant assessment

In the evaluation of recipients with chronic liver disease, the model for end-stage liver disease (MELD) score is commonly used as an indicator of liver decompensation; a higher MELD score reflects a more critically ill recipient with increased metabolic demands. Alongside this, the functional reserve and performance status of other organs are also assessed. As part of the preoperative planning for living donor liver transplantation, it is essential to evaluate the degree of PH. Key preoperative factors such as spleen size, the extent and distribution of porto-systemic collaterals, and the condition of the PV (including its diameter and presence of thrombosis) are crucial in predicting intra-operative portal haemodynamics. These parameters help anticipate potential complications such as portal hyper-perfusion, which may occur in the presence of a large spleen, significant collateral circulation, and a dilated, patent PV[50,51].

Prediction of peri-operative risks

PH affects both the pre-transplant evaluation and the management of peri-operative risks during liver transplantation.

Increased risk of bleeding: One of the primary concerns for patients with PH during transplantation is bleeding, especially from varices or disrupted blood vessels in the liver. High portal pressure leads to the formation of oesophageal and gastric varices, which are prone to bleeding during surgery. By accurately measuring portal pressure, the surgical team can predict these potential complications and take preventive measures, such as performing preoperative endoscopic banding or administering vasoactive drugs to reduce portal pressure prior to surgery.

Splanchnic vasodilation and hypotension: Elevated portal pressure is often linked to splanchnic vasodilation, which can result in hypotension, particularly in the peri-operative period. This condition increases the risk of hemodynamic instability during surgery. Knowing the extent of PH allows for better guidance in fluid management, vasopressor use, and close monitoring of the patient's condition during anaesthesia and the surgical procedure.

Post-transplant monitoring

Accurately measuring portal pressure plays a pivotal role in detecting two primary post-transplant issues: (1) Graft dysfunction; and (2) The recurrence of PH.

Identifying graft dysfunction: A notable increase in portal pressure after transplantation can be an early indicator of graft dysfunction, which may result from ischemic injury, biliary complications, or immune rejection. Monitoring portal pressure in the post-transplant period serves as a signal that the graft might not be functioning as expected. Early intervention in response to elevated portal pressure, whether due to vascular issues or rejection, can help improve graft survival and patient outcomes.

Recurrence of PH: PH can re-emerge following liver transplantation leading to worsening ascites/graft dysfunction likely due to vascular complications. Regular post-transplant portal pressure monitoring is essential for early detection of recurrence, enabling timely medical treatment or, in severe cases, consideration of re-transplantation/surgical intervention.

Evaluating the risk of PV thrombosis: An increase in portal pressure after liver transplantation may also indicate the development of PV thrombosis, a serious condition that can impair graft function. PV thrombus can disrupt portal blood flow, worsening PH and contributing to graft dysfunction. Monitoring portal pressure helps detect PV thrombosis early, allowing for prompt treatment options such as anticoagulation therapy or surgical intervention, both of which can improve graft function and prevent further complications[39,40].

CONCLUSION

Effective assessment and management of portal pressure is crucial in management of patients with cirrhosis of liver and during surgical decisions especially liver transplantation. Despite being considered as the gold standard, the use of HVPG has inherent limitations like heterogeneity, indirect measurement of portal pressure and fallacious readings in pre-sinusoidal causes of PH. With advances in endo-hepatology, EUS guided portal pressure measurement has emerged as a safe and more feasible technique in patients with PH. Pre-operative assessment of PH before liver transplant can help per-operative complications like portal hyper-perfusion, hypotension secondary to splanchnic vasodilatation. Similarly, the measurement of portal pressure measurement in post-transplant setting helps in reducing the risk of graft dysfunction, prediction of PV thrombosis and early detection of PH recurrence. EUS can be performed alongside routine evaluation for varices or liver lesions, thus reducing the procedural burden. In future, randomized controlled trials are required for establishing the clinical efficacy and comparative analysis between EUS-PPG and HVPG. Besides, robust studies are needed to elucidate correlation between EUS-PPG and liver biopsy or non-invasive scores like FIB-4.