Spleen stiffness is positively correlated with HVPG and decreases significantly after TIPS implantation

doi:10.1016/j.dld.2017.09.138

Digestive and Liver Disease

Volume 50, Issue 1, January 2018, Pages 54-60

This manuscript is dedicated to the 65th anniversary of Professor Guido Gerken (Head of the Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany)

https://doi.org/10.1016/j.dld.2017.09.138 Get rights and content

Abstract

Background

Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in patients with decompensated portal hypertension (PH). Hepatic venous pressure gradient (HVPG) is considered gold standard for assessment of PH. Because HVPG measurement is invasive, non-invasive methods for evaluating severity of PH are warranted.

Patients and methods

We retrospectively correlated spleen stiffness as measured by FibroScan with HVPG in patients who underwent TIPS. Twenty-four patients with spleen stiffness measurement (SSM) one day before (D-1), one day after (D + 1) and 28 days after TIPS (D + 28) were included.

Results

SSM was positively correlated with pre-TIPS HVPG (HVPG <13 mmHg, median SSM: 19.7 ± 8.6 kPa; HVPG 13–24 mmHg, median SSM: 45.0 ± 15.7 kPa; HVPG >24 mmHg, median SSM: 75.0 ± 6.2 kPa; p < 0.05]; r² = 0.72; p < 0.001) and decreased significantly after TIPS implantation (D-1, median SSM: 67.1 ± 17.3 kPa; D + 1, median SSM: 44.7 ± 18.5 kPa; D + 28, median SSM: 35.6 ± 17.0 kPa; p < 0.05), while liver stiffness measurement decrease was not statistically significant.

Conclusions

Our study highlights the utility of SSM as non-invasive tool in patients with chronic liver disease in evaluating degree of PH potentially offering a confirmable additional parameter in surveillance of patients undergoing TIPS procedure.

Introduction

Portal hypertension (PH) is a major complication of liver cirrhosis and the most prominent contributing factor for the development of ascites, hepatic encephalopathy, splenomegaly and variceal hemorrhage, resulting in an increase in both morbidity and mortality [1], [2], [3]. Measurement of the hepatic venous pressure gradient (HVPG) is currently considered as the gold standard for determining the severity of PH [4], [5], [6]. Complications of portal hypertension, i.e. development of esophageal varices, may start when HVPG increases over 10 mmHg, which defines what is known as “clinically significant portal hypertension” (CSPH, Baveno IV) [7]. When HVPG increases over a threshold value of 10–12 mmHg, clinical decompensation in form of bleeding, ascites, hepatic encephalopathy, and renal impairment may develop (“decompensated portal hypertension”, DPH) [8]. However, the clinical relevance of HVPG is limited by its invasiveness and the resulting restriction to tertiary centers in many countries.

Non-invasive tools to diagnose PH and estimate its severity are essential and of clinical interest. Recently, spleen- and liver stiffness measured either by transient elastography (TE) or shear-wave elastography (SWE) have become methods of interest with good reliability in detecting PH [8], [9], [10], [11]. In this regard, measurement of the spleen stiffness (compared to liver stiffness) reflects more accurately the dynamic changes concerning the splanchnic circulation occurring in advanced stages of cirrhosis [12], [13].

Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure in the treatment of complications of PH by reducing the portal pressure, indications include bleeding from esophageal or gastric varices, ascites or type-2 hepatorenal syndrome refractory to pharmacological and endoscopic therapy [14], [15], [16]. One of the classical complications of TIPS treatment was secondary shunt occlusion. Recently, the availability of polytetrafluoroethylene (PTFE)-covered stents was an essential step forward by markedly improving the long-term patency of TIPS [17], [18]. Color Doppler sonography is widely used to survey patency by measuring flow velocity in the TIPS. However, it cannot provide information regarding the changes in hydrostatic pressure induced by first PH and secondly by implantation of TIPS as would HVPG measurement [19].

Taking into account the relationship between spleen stiffness and the grade of PH, we aimed to investigate whether (i) spleen stiffness measured by TE correlates with HVPG and (ii) spleen stiffness decreases after TIPS implantation.

Section snippets

Patients and methods

The ethics committee of the University Hospital Essen approved the anonymous analysis of this retrospectively collected data. The study has been conducted according to the principles expressed in the Declaration of Helsinki. For all patients included in the study informed consent was obtained.

Patient characteristics

Of 38 patients who underwent TIPS implantation between 2015 and 2017, 14 (36.8%) were excluded from analysis because of invalidated stiffness measurements (n = 10) and other reasons as demonstrated in (Fig. 1). Invalid SSM at any time-point (D-1, D + 1, D + 28) were obtained in 10 patients: 8 patients had peri-splenic ascites, one patient did not meet manufacturer’s recommendations (IQR >30%, success rate <60%), and one patient previously underwent splenectomy, respectively. The majority of the

Discussion

In this retrospective study, we analyzed SSM of 24 cirrhotic patients undergoing TIPS procedure at the University Hospital Essen between 07/2015 and 02/2017. SSM was performed one day before (D-1), one day after (D + 1) and four weeks after TIPS implantation (D + 28). We compared SSM to angiographically measured HVPG and portal pressure and analyzed the course of SSM after TIPS placement.

Cirrhotic or sinusoidal PH can reliably be evaluated by measuring the HVPG via hepatic vein catheterization and

Conflict of interest

None declared.

Financial support

Nothing to declare.

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Cited by (50)

Relationship Between Spleen Pathologic Changes and Spleen Stiffness in Portal Hypertension Rat Model
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The aim of the study described here was to explore the influence of splenic pathology and hemodynamic parameters on spleen stiffness in portal hypertension (PH).
A Sprague‒Dawley rat model of PH (n = 34) induced by CCl₄ was established, and 9 normal rats were used as controls. All animals underwent a routine ultrasound examination, spleen stiffness measurement (SSM), liver stiffness measurement (LSM), portal vein pressure (PVP) measurement and histopathologic assessment. The diagnostic performance of SSM and LSM in PH was evaluated. SSMs were compared among the groups at different pathologic and hemodynamic levels. Multiple linear regression was used to analyze the factors affecting SSM.
SSM had excellent diagnostic efficacy for PH (area under the receiver operating characteristic curve [AUC] = 0.900) and was superior to LSM (AUC = 0.794). In a rat model of PH, pathologic changes such as splenic sinus widening, thickening of the splenic capsule and an increase in collagen fibers were observed in the spleen. There were significant differences in SSM at different splenic capsule thicknesses and splenic sinus widths (all p values <0.05), but there were no significant differences in the SSM at different levels of the splenic collagen fiber area and red pulp area (all p values >0.05). In addition, there were significant differences in SSM at different levels of portal vein diameter, blood flow and congestion index (all p values <0.05). Multiple linear regression analysis revealed that PVP, portal vein congestion index and splenic capsule thickness were significantly associated with SSM.
SSM is a good non-invasive way to assess PH. PVP, splenic capsule thickness and portal vein congestion index are responsible for spleen stiffness but not the proliferation of splenic fibrous tissue.
Spleen Stiffness Measurement Across the Spectrum of Liver Disease Patients in Real-World Practice
2023, Journal of Clinical and Experimental Hepatology
Spleen stiffness measurement (SSM) provides a non-invasive surrogate marker for clinical significant portal hypertension (CSPH). Results obtained in highly selected populations were promising but require validation across the spectrum of liver disease. We aimed to investigate the clinical applicability of SSM in a real-world setting.
We prospectively enrolled patients referred for liver ultrasound (January–May 2021). Patients with a portosystemic shunt, liver transplant, or extrahepatic etiology of portal hypertension were excluded. We performed liver ultrasound, liver stiffness measurement (LSM) and SSM (dedicated software, 100 Hz-probe). Probable CSPH was established if ≥1 of the following items occurred: ascites, varices, encephalopathy, splenomegaly, recanalized umbilical vein, collaterals, dilated portal veins, hypertensive gastropathy, or LSM ≥25 kPa.
We enrolled 185 patients (53% male; age 53years [37–64], 33% viral hepatitis, 21% fatty liver disease). Of them, 31% of patients had cirrhosis (68% Child-Pugh A) and 38% of patients had signs of portal hypertension. SSM (23.8 kPa [16.2–42.3]) and LSM (6.7 kPa [4.6–12.0]) were successful and met reliability criteria in 70% and 95%, respectively. Spleen size was inversely associated with SSM failure (odds ratio: 0.66 increment/cm, 95% confidence interval: 0.52–0.82). Optimal spleen stiffness cut-off to detect probable CSPH was >26.5 kPa (likelihood ratio: 4.5, sensitivity: 83%; specificity: 82%). Spleen stiffness did not outperform liver stiffness in detecting probable CSPH (P = 1.0).
In real-world practice, reliable SSM were obtained in 70% and could potentially stratify patients between high- and low-risk of probable CSPH. However, cut-offs for CSPH might be substantially lower than previously reported. Future studies validating these results are required.
Netherlands Trial Register (Registration number: NL9369).
Noninvasive Detection of Clinically Significant Portal Hypertension in Compensated Advanced Chronic Liver Disease
2021, Clinics in Liver Disease
Citation Excerpt :
Of note, beta-blockers were previously shown not to affect the diagnostic accuracy of SSM.130 SSM has also been repeatedly shown to decrease after transjugular intrahepatic portosystemic shunt and, therefore, could be a reliable tool to monitor transjugular intrahepatic portosystemic shunt function,131–135 except when there is concurrent embolization or thrombosis of competitive shunts, where SSM may increase after transjugular intrahepatic portosystemic shunting.136 In a recent study by Takuma and colleagues,137 SSM by virtual touch quantification increased after balloon-occluded retrograde transvenous obliteration and was a predictor of exacerbation of esophageal varices.
Predicting the risk of post-hepatectomy portal hypertension using a digital twin: A clinical proof of concept
2021, Journal of Hepatology
Citation Excerpt :
However, the ratio we chose (QPV = 4xQHA) was validated by the flow rate observed in the Fflowmet group (ratio: 4.5). Finally, we did not integrate liver stiffness into our 0D model (because of lacking data in non-cirrhotic patients) even though this parameter is correlated with PCG32 and postoperative outcomes.33,34 This may offer a new approach for more refined development, particularly because, to date, we have adjusted PV elasticity to the fibrosis grade shown in the pathological report, but this information is not always available prior to surgery.
Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (P_PV) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT).
We prospectively included 47 patients undergoing major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n = 9), intraoperative flowmetry (n = 16), or estimated from cardiac output (n = 47). Resection was then simulated in these 3 groups and the computed P_PV and PCG were compared to intraoperative data.
Simulated post-hepatectomy pressures did not differ between the 3 groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated P_PV values was good (r = 0.66, no adjustment to intraoperative events) or excellent (r = 0.75) after adjustment, as well as for PCG (respectively r = 0.59 and r = 0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3 mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures.
We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes.
Post-hepatectomy portal hypertension is a major cause of liver failure and death, but no tool is available to accurately anticipate this potentially lethal complication for a given patient. Herein, we propose using a mathematical model to predict the portocaval gradient at the end of liver resection. We tested this model on a cohort of 47 patients undergoing major hepatectomy and demonstrated that it could modify current surgical decision-making algorithms.
Spleen stiffness can be employed to assess the efficacy of spontaneous portosystemic shunts in relieving portal hypertension
2020, Annals of Hepatology
Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure after transjugular intrahepatic portosystemic shunt (TIPS) placement. However, there is no data available regarding SS in patients with spontaneous portosystemic shunting (SPSS), especially in regards to prediction of hepatic decompensation.
We retrospectively selected patients with confirmed SPSS and esophageal varices (EVs) at endoscopic examination, and recorded any decompensating event (i.e., variceal hemorrhage, overt hepatic encephalopathy, refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) in the first twelve months following liver and spleen elastography.
The patients who presented decompensating events showed lower platelet count (94.5 vs. 121.5 g/L, p < 0.001), higher SS (44 vs. 30 kPa, p < 0.001), higher probability of EVs according to SS (77 vs. 2 %, p < 0.001), and higher spleen diameter (14 vs. 12 cm, p = 0.043). They also showed a higher prevalence of splenorenal shunts (66.7 vs. 31.2%), and a significantly wider SPSS major diameter (14.5 vs. 8 mm, p < 0.001).
SS could predict SPSS efficacy in relieving portal pressure, and could predict decompensating events in patients with SPSS.
Fibrosis Progression in Patients with Budd&amp;#x2013;Chiari Syndrome and Transjugular Intrahepatic Portosystemic Shunt (TIPS): A Long-Term Study Using Transient Elastography
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Liver, Pancreas and Biliary TractSpleen stiffness is positively correlated with HVPG and decreases significantly after TIPS implantation

Abstract

Background

Patients and methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Patient characteristics

Discussion

Conflict of interest

Financial support

J Hepatol

Lancet Lond Engl

Gastroenterology

J Hepatol

J Hepatol

Gastroenterology

Gastroenterology

Dig Liver Dis

Clin Imaging

J Hepatol

Portal hypertension and gastrointestinal bleeding

Semin Liver Dis

Assessing portal hypertension in liver diseases

Expert Rev Gastroenterol Hepatol

The clinical use of HVPG measurements in chronic liver disease

Nat Rev Gastroenterol Hepatol

Spleen and liver stiffness is positively correlated with the risk of esophageal variceal bleeding

Digestion

Liver, Pancreas and Biliary Tract
Spleen stiffness is positively correlated with HVPG and decreases significantly after TIPS implantation