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SAGE Open Med
. 2023 Oct 29;11:20503121231208655. doi: 10.1177/20503121231208655

Clinical outcomes related to portal pressures before and after embolization of large portosystemic shunts in cirrhosis

Sasidharan Rajesh

Sasidharan Rajesh

1Interventional Hepatobiliary Radiology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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1, Cyriac Abby Philips

Cyriac Abby Philips

2Clinical and Translational Hepatology and Monarch Liver Laboratory, The Liver Institute, Center for Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India
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2,✉, Rizwan Ahamed

Rizwan Ahamed

3Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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3, Shobhit Singh

Shobhit Singh

1Interventional Hepatobiliary Radiology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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1, Jinsha K Abduljaleel

Jinsha K Abduljaleel

3Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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3, Ajit Tharakan

Ajit Tharakan

3Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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3, Philip Augustine

Philip Augustine

3Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
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3

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1Interventional Hepatobiliary Radiology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
2Clinical and Translational Hepatology and Monarch Liver Laboratory, The Liver Institute, Center for Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India
3Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Kerala, India
✉
Cyriac Abby Philips, Department of Clinical and Translational Hepatology, The Liver Institute, Center for Excellence in Gastrointestinal Sciences, Ground Floor, Phase II, Tower-3, Rajagiri Hospital, Aluva, Kerala 683112, India. Email: abbyphilips@theliverinst.in
Received 2023 Feb 25; Accepted 2023 Oct 3; Collection date 2023.
© The Author(s) 2023
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
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PMCID: PMC10617273 PMID: 37915841

Abstract

Objectives:

Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown.

Methods:

In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes.

Results:

Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion (p < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four (N = 42, 9.5%) patients at 6–12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively.

Conclusion:

Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation.
Keywords: HVPG, variceal bleeding, CSPH, portal hypertension, HCC

Introduction

Portosystemic shunt syndrome (PSS) in patients with cirrhosis represents a distinct and critical aspect of the disease's natural progression. Large portosystemic shunts (PSs) are frequently linked to significant complications, including gastric variceal bleeding (GVB) and spontaneous hepatic encephalopathy (HE). These shunts can also contribute to recurrent GVB, inadequate bleeding control, and persistent or frequently recurring HE, often leading to repeated hospitalizations and a diminished quality of life for affected individuals.[1, 2]

Historically, spontaneous PSS (SPSS) in advanced cirrhosis was viewed as a beneficial "decompressing channel" for progressive portal hypertension. However, contemporary research has refuted this notion, demonstrating a clear association between large shunts and the worsening of liver disease and increased severity of portal hypertension. The presence of large shunts, as detected by contrast cross-sectional imaging, has been directly correlated with higher mortality rates and an increased risk of complications.[3, 4]

Further research indicates that the total cross-sectional area of SPSS, rather than the diameter of a single large shunt, serves as a more accurate predictor of adverse outcomes, including the onset of HE or mortality, even in patients with preserved liver function.[5] Consistent, high-quality studies have shown that embolization of large PS in cirrhosis effectively controls GVB and significantly reduces the frequency and occurrence of overt HE. Anecdotal evidence also suggests that early occlusion of large PS offers greater benefits than delayed or no embolization in cirrhotic patients experiencing recurrent or refractory HE.[6]–[8]

While shunt embolization is generally considered a safe procedure with typically mild, self-limiting local complications, some concerns exist regarding its potential to exacerbate portal hypertension and worsen variceal disease. Conversely, other studies have reported that an increase in portal pressures, reflected by elevated post-procedure hepatic venous pressure gradient (HVPG), may correlate with improved liver function. For instance, Tanihata et al. demonstrated that balloon-occluded retrograde transvenous obliteration (BRTO) of gastric varices could worsen esophageal varices, attributing this to a post-procedure increase in portal pressure systemic gradient exceeding 5 mm Hg.[9]

In a debated study, Uehara et al. suggested that an HVPG increase of over 20% from baseline was predictive of improved liver function following shunt embolization.[10] This contrasts with findings by Park et al., who observed that embolization of large PS led to an increase in HVPG, carrying a significant risk of symptomatic esophageal variceal progression. Although liver function improved over a 6-month follow-up period in their study, the relationship to portal pressure changes was complex.[11]

Existing literature primarily focuses on HVPG-related changes and complications of portal hypertension, particularly variceal disease, after shunt embolization, often from small cohort studies. A notable gap remains in comprehensive studies assessing overall clinical outcomes in the context of pre- and post-shunt embolization HVPG changes. This includes an analysis of liver-related events (such as GVB, ascites, HE, shunt recurrence, and hepatocellular carcinoma (HCC)) and non-liver related events (like sepsis, short-term, and overall mortality) among cirrhotic patients undergoing shunt embolization for GVB, HE, or both. Our study aims to address this critical knowledge gap.

Methods

Patients

This study retrospectively included all patients aged 18 years and above diagnosed with cirrhosis and portal hypertension who underwent shunt embolization at our tertiary liver disease treatment center in Kochi, Kerala, India. Patients were included if they presented with recurrent or persistent hepatic encephalopathy (HE), recurrent or difficult-to-control gastric variceal bleeding (GVB), or both, and had HVPG measurements meticulously performed before and after the procedure according to a strict protocol. We excluded patients who underwent embolization but did not consent to HVPG measurement per protocol, those with only one HVPG measurement, or those with incomplete documentation or follow-up.

All included patients completed a minimum follow-up of one year, extending up to a maximum of 32 months from the procedure, or until death or liver transplantation, whichever occurred first. Patients who underwent shunt embolization concurrently with transjugular intrahepatic portosystemic shunt (TIPS) placement were excluded. Furthermore, patients with shunt-related HE or variceal bleeding who had been previously treated for liver cancer or were diagnosed with liver cancer during their evaluation for shunt syndrome were not considered for inclusion. We also excluded patients with acute on chronic liver failure, recurrent or refractory ascites requiring paracentesis, uncontrolled sepsis, refractory septic or hypovolemic shock, multiple organ failure, main portal vein trunk thrombosis (malignant or non-malignant), multiple shunts presenting high technical challenges, or those already candidates for liver transplantation. This rigorous selection ensured a homogeneous cohort for analysis.

Statistical analysis

Statistical analysis was conducted using MedCalc Statistical Software (Ostend, Belgium). Data are presented as mean and standard deviation or as median with an interquartile range. One-way analysis of variance was employed to assess baseline differences between the means of investigational variables across groups. A p -value of < 0.05 was considered statistically significant. Fisher’s exact test was used for comparing nominal variables, especially with small sample sizes, while Mann–Whitney’s U test was applied for continuous variables. Due to the limited sample size, exact logistic regression was utilized to identify independent mortality-related parameters, employing the Cox-Snell R [2] method.[12] Patient survival probabilities up to the study endpoints were determined using the Kaplan–Meier method and visually represented by survival time curves.

Primary and secondary outcome measures

The Hepatic Venous Pressure Gradient (HVPG) in mm Hg was systematically measured in all patients before and after shunt embolization, adhering to established and validated protocols.[9, 10] We calculated both the absolute elevation in HVPG from baseline and the percentage change in HVPG following shunt embolization for all participants. Patients were subsequently categorized based on median HVPG values (pre- and post-shunt embolization), absolute HVPG elevation, and percentage HVPG change for comparative analysis. Our primary objective was to assess survival at the 1-year mark post-procedure. Secondary outcome measures included survival at 32 months (exceeding 2 years), progression of esophageal varices, infections necessitating hospital admission within 100 days and beyond 12 months post-procedure, and the incident development of ascites, HE, or HCC after the intervention.

Procedures

All procedures were performed under local anesthesia after obtaining written informed consent. Access was gained via the right common femoral vein or internal jugular vein, where a 6F vascular access sheath (Cook, Bloomington, Indiana) was positioned. HVPG was then precisely measured using the standard balloon wedge technique. Subsequently, the portosystemic shunt (PS) was cannulated using a combination of a 5F angiographic catheter (multipurpose or cobra; Cook) and a 0.035″ hydrophilic J-tipped guidewire (Radifocus; Terumo, Japan).

The catheter was then exchanged for a flexible curved sheath (Flexor Check-Flo Introducer with large valve assembly, Mullin design, and Ansel modification, 7F-14F; Cook) advanced over a 260 cm, 0.035″ Amplatz ultra-stiff guidewire (Cook, Inc.). Venography was performed through the sheath to precisely delineate the shunt anatomy and confirm proper sheath placement. The specific embolization modality—Balloon-Occluded Retrograde Transvenous Obliteration (BRTO), Plug-Assisted Retrograde Transvenous Occlusion (PARTO), or Coil-Assisted Retrograde Transvenous Occlusion (CARTO), with or without glue instillation—was determined by the interventional radiologist based on pre-procedural imaging and adherence to standardized techniques.[6, 7]

For balloon-assisted shunt occlusion, an appropriately sized compliant balloon catheter (Equaliser, Boston Scientific Corporation, Natick, MA, USA) was meticulously positioned within the shunt. After ensuring no contrast leakage around the inflated balloon, a sclerosing agent (prepared by mixing lipiodol, 3% sodium tetradecyl sulfate (STS; SETROL, Samarth Life Sciences, Mumbai, India), and air in a 1:2:3 ratio) was infused to completely fill the shunt. The balloon remained inflated for 4 hours to facilitate effective sclerosis and occlusion.

In cases of plug-assisted shunt occlusion, an amplatzer vascular plug (AVP-II; St. Jude Medical, Inc., St. Paul, MN, USA or Cera-Vascular plug, Lifetech Scientific, Shenzhen, China; 8–24 mm) with a diameter 30%–50% larger than the shunt's narrowest accessible point was deployed. A 2.7 Fr microcatheter (Progreat, Terumo, Japan) was simultaneously maintained distal to the plug within the shunt. A venogram via the microcatheter confirmed complete occlusion and identified any additional efferent channels requiring embolization. Subsequently, a sclerosant mixture of 3% STS and contrast (320 mg I/ml; Visipaque, GE Healthcare, Ireland) in a 2:1 ratio, augmented with small gel foam pieces, was injected under fluoroscopic visualization until complete shunt filling was achieved. The plug was then deployed, and all catheters and sheaths were withdrawn.

For coil-assisted shunt occlusion, a procedure analogous to the plug method was followed, but oversized detachable coils (Interlock-35 Fibered IDC Occlusion System, Boston Scientific, USA) were used as the primary occluding agent. HVPG measurement was re-evaluated the following day, within 24 hours, after confirming complete obliteration of the PS via contrast-enhanced cross-sectional imaging. The study was conducted in accordance with the Helsinki Declaration of 1975 (as revised in 2000 and 2008) regarding human rights. The institutional review board of the Liver Institute, Rajagiri Hospital (CoEGIS/TLI/RAJH:83/12/2022), approved both the study design and the retrospective collection of patient data. The Institutional Review Board/Ethics Committee waived the requirement for obtaining consent from a legally authorized representative for deceased patients due to the retrospective, pooled analysis nature of the study, which precluded individualistic scrutiny of existing clinical data.

Post-procedure protocol and follow-up

All patients were maintained on optimized beta-blockers (either carvedilol or propranolol, chosen by the treating physician) both before and after shunt embolization. For patients with grade ≥2 ascites, either pre- or post-procedure, a low-sodium diet and diuretics were initiated. Those who developed symptomatic grade 3 ascites received large-volume paracentesis, supplemented with intravenous human albumin infusion as clinically indicated. All patients experiencing hepatic encephalopathy (HE) continued on rifaximin (550 mg twice daily) and oral lactulose (titrated to achieve at least two soft stools per day). Patients who developed de novo HE post-shunt embolization were commenced on secondary prophylaxis. Notably, no patients received weekly human albumin infusions before or after shunt embolization.

To assess variceal disease progression, all patients underwent upper gastrointestinal endoscopy between 1 and 3 months post-procedure, followed by surveillance every 3 to 6 months for the first year, and annually thereafter. Contrast-enhanced computed tomography of the abdomen was performed 24 hours post-procedure to confirm shunt occlusion, with subsequent scans at 6 months, 1 year, and 2 years. The most recent imaging report informed the study's imaging-based variables. All included patients were meticulously followed for a minimum of 1 year and a maximum of 32 months, or until death or liver transplantation (both considered negative outcomes), whichever occurred first.

Results

Patients inclusion

Between January 2018 and October 2020, our center performed shunt embolization on 99 cirrhosis patients presenting with portosystemic shunt syndrome (PSS) for various indications. Of this cohort, 32 patients who underwent shunt embolization alongside transjugular intrahepatic portosystemic shunt (TIPS) placement were excluded. Additionally, 3 patients previously treated for hepatocellular carcinoma (HCC) or diagnosed with HCC during their evaluation for shunt embolization were also excluded. From the remaining 64 patients who underwent shunt embolization exclusively, 9 did not receive HVPG measurements, 4 had only one HVPG measurement recorded, and 5 had incomplete documentation or follow-up data, leading to their exclusion from the final analysis. Ultimately, 46 patients (34 for HE, 11 for GVB, and 1 for both) with comprehensive pre- and post-shunt embolization HVPG measurements were included in this study (Figure 1).

Figure 1.

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Details of patients included in the study.

Patients characteristics

The study cohort predominantly consisted of males (N = 39, 84.8%), with a mean age of 58.02 ± 8.71 years. The primary etiology of cirrhosis in the majority of patients (N = 35, 76.1%) was metabolic-dysfunction-associated fatty liver disease. Systemic hypertension was the most prevalent comorbidity, affecting 42 patients (91.3%), and 37 patients (80.4%) were classified as overweight or obese. Baseline median Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores were 7 (IQR 25–75 P, 7–9) and 15.5 (11–19), respectively, indicating varying degrees of liver dysfunction.

A single large portosystemic shunt (PSS) was identified in 38 (82.6%) patients, while the remaining patients presented with dual shunts. The most frequently observed shunt type was lienorenal (N = 25, 54.3%), followed by gastrorenal (N = 7, 15.2%) and large left coronary vein (N = 4, 8.7%) shunts. The median size of the largest shunt across all 46 patients was 15.5 mm (ranging from 7 mm to 35 mm). Of the 11 patients undergoing shunt embolization for gastric variceal bleeding (GVB), type 2 gastro-esophageal varices (GOV2) were present in 10 patients (90.9%), with one patient having isolated gastric varix type 1.

Among patients undergoing shunt embolization for hepatic encephalopathy (HE), indications included recurrent HE in 21 patients (45.7%), a severe first episode of overt HE in 10 patients (21.7%—comprising nine in pre-coma and one in hepatic coma), and persistent HE in four patients (8.7%). Prior to shunt embolization, 10 patients (21.7%) exhibited radiologically (grade 1 in eight) or clinically detectable (grades 2 and 3 in two) ascites. The 1-year survival rate after shunt embolization was 86.96% (N = 46, with 6 deaths, 13.04%, mean survival 47.43 ± 1.9 weeks). At the 32-month follow-up, 21 patients had died (45.65%), yielding a mean survival of 24.59 ± 1.5 months (proportion surviving 54.35%). By 12 months, one patient, and by 32 months, two patients, had successfully undergone liver transplantation (Table 1 and Figure 2).

Table 1.

Complete and pertinent clinical and investigational details at baseline and follow-up of cirrhotic patients undergoing shunt embolization.

| **N ** | Minimum | Maximum | Mean | Median | SD | 25–75 P
---|---|---|---|---|---|---|---
Age (years) | 46 | 40 | 80 | 58.02 | 60 | 8.7 | 51–63
Hemoglobin (g/L) | 46 | 6.8 | 14.2 | 10.6 | 10.8 | 1.9 | 9.1–12.1
White cell count (×103 per cubic mm/L) | 46 | 2.4 | 14.2 | 6.2 | 5.9 | | 4.5–8.4
Platelet count (×103 per cubic mm/L) | 46 | 45 | 178 | 103.8 | 96 | 32.4 | 85–124
Total bilirubin (mg/dL) | 46 | 0.5 | 13.1 | 2.1 | 1.9 | | 1.3–3.1
Serum albumin (g/dL) | 46 | 2.2 | 3.8 | 3.02 | 2.9 | 0.4 | 2.8–3.4
International normalized ratio | 46 | 0.9 | 3.6 | 1.5 | 1.4 | | 1.2–1.7
Serum creatinine (mg/dL) | 46 | 0.6 | 3.9 | 0.9 | 0.9 | | 0.7–1.2
Serum sodium (meq/L) | 46 | 127 | 144 | 134.8 | 135 | 4.5 | 130–138
Child Turcotte Pugh score | 46 | 5 | 13 | 8.1 | 7 | 2.1 | 7–9
Model for end-stage liver disease score | 46 | 6 | 29 | 15.8 | 15.5 | 5.7 | 11–19
Arterial ammonia (μmol/L) | 46 | 24 | 301 | 100.03 | 101.3 | | 74–147
Pre-procedure HVPG (mm Hg) | 46 | 9 | 21 | 13.4 | 13 | 3.2 | 11–15
Post-procedure HVPG (mm Hg) | 46 | 12 | 26 | 16.9 | 16 | 3.6 | 14–19
Percentage change in HVPG from baseline | 46 | 5 | 59 | 28.6 | 28.5 | 13.3 | 18–36
Days in ICU | 15 | 1 | 8 | 2.8 | 3 | | 2–3.7
Size of the largest shunt (in mm) | 46 | 7 | 35 | 14.9 | 15.5 | | 12–19
Time to bleed after the procedure | 5 | 34 | 104 | 58.2 | 69 | | 34.8–83.9
Duration of stay during shunt embolization | 46 | 1 | 19 | 3.4 | 3 | | 2–5
Gender | Males— N = 39, 84.8%
Diabetes/systemic hypertension/obese | N = 29, 63%/N = 4, 8.7%/N = 9, 19.6%
Etiology of liver disease | Non-alcoholic steatohepatitis— N = 35, 76.1%
Grade of esophageal varices (baseline) | 0—6.5%, I—47.8%, II—43.5%, III—2.2%
Grade of esophageal varices (last surveillance) | 0—21.7%, I—26.1%, II—41.3%, III—10.9%
Procedure performed for (indication) | GVB, N = 11, 23.9%; encephalopathy, N = 34, 73.9%; both, N = 1, 2.2%
Type of hepatic encephalopathy (N = 35) | Recurrent, N = 21, 45.7%, first severe overt, N = 10, 21.7%, persistent, N = 4, 8.7%
Gastric varices (baseline) | GOV2— N = 10/11, 90.9%
Number of shunts before the procedure | One in 82.6%, two in 17.4%
Type of shunts identified for embolization | LRS, N = 25, 54.3%GRS, N = 7, 15.2%LCV, N = 4, 8.7%PUV, N = 2, 4.3%MCS, N = 1, 2.2%LRS + GRS, N = 2, 4.3%LRS + LCV, N = 2, 4.3%LRS + MCS, N = 1, 2.2%LRS + PUV. N = 1. 2.2%GRS + PUV, N = 1, 2.2%
Procedure performed (N = 46) | PARTO, N = 13 (28.3%)CARTO, N = 12 (26.1%)BRTO, N = 8, 17.4%CAATO, N = 7, 15.2%CARTO + PARTO, N = 4, 8.7%CAATO + glue, N = 2, 4.3%
Bleeding esophageal varices on follow up | N = 5, 10.9%
Recurrence of shunt on protocol imaging | N = 11, 23.9%
Sepsis within 100 days after the procedure | N = 7, 15.2%Bacteremia (N = 2, 28.6%), pneumonia (N = 2, 28.6%), urinary tract infection (N = 2, 28.6%), spontaneous bacterial peritonitis (N = 1, 14.3%)
Causes of death in the first-year post-procedure | Total, N = 6 (13%): septic shock in four, pulmonary embolism and acute variceal bleeding in one
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SD: standard deviation; LRS: lienorenal shunt; GRS: gastrorenal shunt; LCV: left coronary vein shunt; PUV: paraumbilical vein; MCS: mesocaval shunt.

Figure 2.

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Kaplan–Meier analysis shows the proportion of patients surviving at the end of 1 year and long-term follow-up of 32 months after shunt embolization.

Procedure-related characteristics

Among the various shunt embolization techniques, the Plug-Assisted Retrograde Transvenous Obliteration (PARTO) method was most frequently employed (N = 13, 28.3%). This was followed by Coil-Assisted Retrograde Transvenous Obliteration (CARTO) (N = 12, 26.1%), Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) (N = 8, 17.4%), and Coil-Assisted Antegrade Transvenous Occlusion (N = 7, 15.2%). The transjugular route was the preferred approach in 37 patients (80.4%), while a percutaneous approach was used in 8 (17.4%), and a combination of both in 1 patient (2.2%).

Post-procedure, 15 patients (32.6%) required monitoring in the intensive care unit (ICU). The median duration of ICU stay was 3 days (ranging from 1 to 8 days), and the total hospital stay also averaged 3 days (ranging from 1 to 19 days) (Figure 3). This highlights the acute care needs associated with the procedure, albeit typically for short durations.

Figure 3.

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The various shunt-embolization methods performed in the patient cohort. Large gastric varices (arrow, a) and post-embolization disappearance of varices (asterisk, b) with the development of ascites (arrow, b); large lienorenal shunt occluded using a plug (arrows, c); balloon-assisted retrograde transvenous occlusion of a large shunt (arrow, d); a large bunch of gastric varices (arrow, e) and associated shunt (asterisk, e) and complete occlusion of shunt and associated obliteration of gastric varices (arrows, f).

The hepatic venous pressure gradient (HVPG) measured before shunt embolization averaged 13.4 ± 3.2 mm Hg (median 13, range 9–21). Following shunt occlusion, the HVPG significantly increased to 16.9 ± 3.7 mm Hg (median 16, range 12–26), a statistically significant difference (p < 0.0001, Hodges–Lehmann median difference 3.0). The mean percentage increase in HVPG from baseline was 28.6 ± 13.3%, with a notable range from 5% to 59%. These measurements demonstrate the immediate hemodynamic impact of shunt closure on portal pressures within the liver.

Portal hypertension-related events

Before shunt embolization, 25 patients (54.3%) presented with low-grade (grade 0 or 1) esophageal varices, while 21 patients (45.7%) had high-grade (grade 2 or 3) varices. One year after shunt embolization, among the 40 surviving patients, the proportion of low-grade varices decreased to 42.5%, while high-grade varices increased to 57.5%. At the 32-month follow-up, among the 25 surviving patients, low-grade varices were noted in 40%, and high-grade varices in 60%. Although there was an evident aggravation of variceal disease post-shunt embolization, this trend did not reach statistical significance.

Bleeding from varices occurred in only five patients (10.9%) during the entire follow-up period after shunt embolization. The median time to a bleeding event was 69 weeks (ranging from 34 to 104 weeks). Prior to shunt embolization, 10 patients (21.7%) had significant ascites (grade 1 in eight, grades 2 and 3 in two). Post-shunt embolization, clinically significant ascites developed in 12 patients (26.1%) within 6 months and in 5 patients (11.9%) between 6 and 12 months (data for 4 deceased patients were unknown). Similarly, overt hepatic encephalopathy (HE) post-shunt embolization was observed in three patients (6.5%) within 6 months and in four patients (9.5%) between 6 and 12 months. Recurrence of portosystemic shunts (PSS) on protocol imaging during follow-up was noted in 11 patients (23.9%).

Clinical events and significance related to outcomes

Infections necessitating hospital admission were observed in 7 patients (15.2%) within 100 days after shunt embolization and in 14 patients (30.4%) over the entire 32-month follow-up period. Within the first 100 days post-procedure, the most common infection sites were bacteremia and lung infections (two cases each, 28.6%), followed by urinary tract infection (two cases, 28.6%) and spontaneous bacterial peritonitis (one case, 14.3%). During the first year post-procedure, 6 patients (13%) died: 4 (66.7%) due to septic shock, and one each due to acute variceal bleeding and massive pulmonary embolism. By the end of the 32-month follow-up, a total of 21 patients (45.7%) had died after the shunt embolization procedure.

The incidence of hepatocellular carcinoma (HCC) on overall follow-up, specifically beyond the first year post-shunt embolization, was noted in 7 patients (15.2%). The occurrence of infections within 100 days following shunt embolization was significantly associated with 1-year mortality (p = 0.003), though this association did not hold for overall mortality at 32 months (p = 0.68). However, infections requiring hospitalization beyond the first year after shunt embolization were significantly linked to increased mortality (relative risk 2.7, 95% confidence interval 1.54–4.76, p < 0.001). Multivariate regression analysis further confirmed that only infection occurring beyond 12 months post-shunt embolization was an independent predictor of mortality (p = 0.001, odds ratio 4.1, 95% CI 1.68–9.72). Neither Child-Turcotte-Pugh (CTP) nor Model for End-Stage Liver Disease (MELD) scores were significantly associated with shunt recurrence or long-term overall mortality in this cohort.

Significant HVPG-associated outcomes

Patients were categorized into groups based on their HVPG measurements: ⩽13 mm Hg or >13 mm Hg pre-procedure, and ⩽16 mm Hg or >16 mm Hg post-procedure, using median value cutoffs. A post-shunt embolization HVPG exceeding 16 mm Hg was significantly associated with the development of ascites between 1 and 6 months post-procedure (relative risk 1.6, 95% CI 1.1–2.3, p = 0.01). Similarly, an increase in HVPG of more than 4 mm Hg from baseline also significantly predicted the development of ascites within 1 to 6 months following the occlusion of large portosystemic shunts (p = 0.02).

However, neither baseline nor post-procedure HVPG cutoffs showed a significant association with ascites development between 6 and 12 months after shunt embolization. The occurrence of post-procedure overt hepatic encephalopathy (HE) at both 1–6 months and 6–12 months was not significantly influenced by HVPG cutoffs, whether at baseline or after the procedure. Similarly, the development of sepsis within 100 days and beyond 12 months post-shunt embolization was not significantly impacted by HVPG cutoffs. The incidence of hepatocellular carcinoma (HCC) beyond the first year post-shunt embolization did not show a statistically significant relationship with a post-procedure HVPG above 16 mm Hg (relative risk 1.3, 95% CI 0.99–1.67, p = 0.053). Notably, the percentage change in HVPG from baseline was not significantly associated with any of the outcome measures analyzed in this study (Figure 4).

Figure 4.

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The significance of pre- and post-procedure portal pressures measured as the HVPG on various clinical, investigational, and patient outcomes.

Discussion

Large spontaneous portosystemic shunts (PSS) in cirrhotic patients are strongly linked to hepatic encephalopathy (HE) and reduced transplant-free survival, irrespective of liver function, lower MELD scores, or beta-blocker treatment status.[3] Early embolization of symptomatic large PSS in the disease course has shown promise in improving clinical outcomes, particularly in achieving better control of gastric variceal bleeding and preventing HE recurrence.[13] Previous studies on shunt embolization have explored clinical and investigational variables related to outcomes. For instance, MELD scores above 11–15 and CTP scores above 11 were associated with negative outcomes, while liver stiffness values below 21.6 kPa pre-embolization correlated with improved survival and fewer adverse events. Moreover, early shunt embolization was consistently linked to enhanced transplant-free survival.[14]

Our current study provides novel insights by examining the association between portal pressures, both before and after shunt embolization, and short-term and long-term clinical outcomes in a substantial single-center patient series. This represents the largest cohort to date with sequential HVPG measurements, incorporating various advanced shunt embolization techniques. We found a 1-year survival rate of approximately 87% and a remarkable 55% survival rate beyond 2.5 years. Critically, the development of infections (sepsis) within 100 days and beyond the first year post-embolization was significantly associated with mortality at 12 and 32 months, respectively.

Infections requiring hospital admission emerged as the sole independent predictor of long-term mortality in cirrhotic patients undergoing shunt embolization. Furthermore, our findings indicate that an HVPG elevation of more than 4 mm Hg from baseline, and an absolute increase to over 16 mm Hg immediately post-procedure, significantly predicted the development of early- and late-onset ascites, respectively. While an absolute HVPG increase above 16 mm Hg post-embolization also showed a trend toward an increased incidence of primary liver cancer, the percentage change in HVPG from baseline did not influence any clinical outcomes.

Tanihata and colleagues previously demonstrated that an HVPG elevation exceeding 5 mm Hg after shunt embolization (specifically using BRTO) significantly exacerbated esophageal varices. They noted that the presence of varices and higher grades (grade 2 > grade 1) at baseline were key predictors of worsening variceal disease, particularly in CTP class B patients.[9] In our study, although variceal disease aggravation was evident post-procedure, only 1 in 10 patients experienced bleeding during follow-up. This favorable outcome is likely attributable to two factors: consistent beta-blocker optimization both before and after shunt embolization, and the utilization of superior embolization techniques (such as PARTO, CARTO with or without glue) that ensured comprehensive occlusion of the variceal complex and its tributaries, thereby mitigating significant clinical events despite variceal aggravation.

Uehara et al. controversially reported that an HVPG increase of ≥20% from baseline correlated with improved liver function, with no significant HE or bleeding post-BRTO.[10] However, their study lacked clear explanations for these contradictory findings and may not have adequately controlled for confounding variables. Current literature consistently links HVPG to an increased risk of variceal bleeding, ascites, infections, HE, liver disease progression, and HCC development.[14, 15] Despite this, robust data specifically on HCC risk in the context of shunt embolization remains scarce. In contrast to Uehara’s findings, and consistent with the prevailing literature, our study demonstrated that HVPG elevation of >4 mm Hg from baseline and an absolute increase to >16 mm Hg were associated with a higher incidence of ascites, reinforcing the link between increased portal pressure and adverse outcomes.

A large multicenter retrospective study from Korea indicated that only CTP class C was associated with rebleeding after shunt embolization, supporting the notion that post-procedure HVPG elevation leads to aggravated portal hypertension events, rather than an amelioration of liver disease severity.[16] Similarly, Park and colleagues reported 100% technical success with PARTO for GVB, but observed variceal worsening in 53% of patients.[11] Their study found a significant association between HVPG and esophageal variceal aggravation, yet it lacked details on beta-blocker optimization and other confounding factors that could explain variceal exacerbation. Although liver function showed initial improvement after PARTO for the first 6 months, this was not significantly linked to portal pressures, suggesting that other factors, such as the control of etiological elements, might have played a role in liver disease improvement.[11]

In our patient cohort, intermediate and long-term outcomes were primarily influenced by the development of infections post-shunt embolization. While a previous study on shunt embolization for HE noted a CTP score above 11 as a predictor of higher mortality in cirrhotics undergoing shunt occlusion,[17] our study likely did not reach statistical significance for this association due to the inclusion of cirrhosis patients with a generally lesser degree of disease severity. A retrospective review from the Royal Free Hospital, London, by Privitera et al., found that patients who did not improve post-procedure often experienced sepsis (20%), developed severe ascites, or had variceal bleeding (approximately 8%).

Privitera et al. did not find an association between pre-procedural MELD score and outcome, suggesting that a MELD score >11 might not be an optimal stratification method, and a significant proportion of patients undergoing shunt embolization still developed portal hypertension-related complications. These findings align with our study, which emphasizes the need for a more detailed patient assessment, including portal pressure measurement, to better identify subgroups at lower risk of complications. In our study, we observed that an absolute increase in HVPG (≥16 mm Hg), a pertinent elevation of HVPG from baseline (>4 mm Hg), and the occurrence of infections post-procedure identified a subgroup of patients at higher risk for negative outcomes, including portal hypertension complications, HCC, and reduced transplant-free survival.

Our study benefits from several strengths, notably its position as the largest single-center study to analyze clinical outcomes in cirrhosis patients undergoing shunt embolization for HE or GVB, specifically in relation to pre- and post-procedure portal pressures. We successfully identified a distinct subgroup of patients who experienced negative outcomes based on their baseline and post-procedure HVPG. These findings suggest that a comprehensive pre- and post-shunt embolization assessment could be crucial for identifying patients who require rigorous monitoring for infections, optimizing risk factors for complications, refining beta-blocker and diuretic therapies to better manage portal hypertension, and implementing close surveillance for the development of hepatocellular carcinoma (HCC). Ultimately, for patients exhibiting such risk factors or developing related complications, early consideration for liver transplantation could significantly improve survival rates (Figure 5, summary infographics).

Figure 5.

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Summary infographics of the study.

However, our retrospective single-center study has inherent limitations that warrant consideration. The findings necessitate validation through well-designed prospective studies to confirm their generalizability and robustness. Further research is also required to realistically assess the influence of beta-blocker therapy and its targeted optimization, ideally through studies incorporating a control group for comparative analysis. Establishing stringent, well-defined inclusion criteria in future studies could greatly assist in identifying specific clinical and investigational variables linked to improved liver function post-shunt occlusion. Finally, due to the retrospective, cross-sectional design, a formal sample size calculation was not performed, and the precise role of different shunt embolization methods on long-term outcomes still requires clearer delineation.

Conclusion

Our study demonstrates that both baseline and post-procedure Hepatic Venous Pressure Gradient (HVPG), along with their dynamic changes, are critical determinants of intermediate and long-term clinical outcomes in cirrhotic patients undergoing shunt embolization for hepatic encephalopathy (HE) or gastric variceal bleeding (GVB). Specifically, an HVPG elevation exceeding 4 mm Hg from baseline and an absolute HVPG increase to ⩾16 mm Hg post-procedure were significantly associated with clinically relevant portal hypertension events. Furthermore, post-shunt embolization sepsis was identified as an independent risk factor for long-term mortality. These findings underscore the importance of meticulous hemodynamic assessment in managing these complex patients.

Footnotes

Author contributions: Sasidharan Rajesh has been involved in conceptualization, methodology, data curation, writing (review and editing), validation; Cyriac Abby Philips has been involved in conceptualization, visualization, methodology, writing (original draft and review), validation; Rizwan Ahamed has been involved in writing (review and editing), validation, supervision; Shobhit Singh has been involved in data curation, writing (review and editing), validation; Jinsha K Abduljaleel has been involved in writing (review and editing), validation, supervision; Ajit Tharakan has been involved in writing (review and editing), validation, supervision; Philip Augustine has been involved in writing (review and editing), validation, and supervision.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics approval: Ethical approval for this study was obtained from the Institutional Review Board of the Liver Institute, Rajagiri Hospital (CoEGIS/TLI/RAJH:83/12/2022). All authors confirm that they are accountable for all aspects of the work (if applied, including full data access, the integrity of the data, and the accuracy of the data analysis) in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Informed consent: The requirement of obtaining consent from a legally authorized representative (in the case of deceased patients) was waived off by the Institutional Review Board/Ethics Committee.
Trial registration: Not applicable as this is not a prospective randomized trial.
ORCID iD: Cyriac Abby Philips https://orcid.org/0000-0002-9587-336X

References

• 1. Saad WE. Portosystemic shunt syndrome and endovascular management of hepatic encephalopathy. Semin Intervent Radiol 2014; 31(3): 262–265. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 2. Philips CA, Ahamed R, Rajesh S, et al. Beyond the scope and the glue: update on evaluation and management of gastric varices. BMC Gastroenterol 2020; 20(1): 361. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 3. Simón-Talero M, Roccarina D, Martínez J, et al. Baveno VI-SPSS group from the Baveno Cooperation. Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis. Gastroenterology 2018; 154(6): 1694–1705.e4. [DOI] [PubMed] [Google Scholar]
• 4. Nardelli S, Riggio O, Turco L, et al. Relevance of spontaneous portosystemic shunts detected with CT in patients with cirrhosis. Radiology 2021; 299(1): 133–140. [DOI] [PubMed] [Google Scholar]
• 5. Praktiknjo M, Simón-Talero M, Römer J, et al. Baveno VI-SPSS group of the Baveno Cooperation. Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis. J Hepatol 2020; 72(6): 1140–1150. [DOI] [PubMed] [Google Scholar]
• 6. Philips CA, Rajesh S, Augustine P, et al. Portosystemic shunts and refractory hepatic encephalopathy: patient selection and current options. Hepat Med 2019; 11: 23–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 7. Philips CA, Rajesh S, George T, et al. Early, late, or no shunt embolization in patients with cirrhosis- and portosystemic shunt-related hepatic encephalopathy. Indian J Gastroenterol 2020; 39(4): 377–387. [DOI] [PubMed] [Google Scholar]
• 8. Maydeo A, Patil G. How to approach a patient with gastric varices. Gastroenterology 2022; 162(3): 689–695. [DOI] [PubMed] [Google Scholar]
• 9. Tanihata H, Minamiguchi H, Sato M, et al. Changes in portal systemic pressure gradient after balloon-occluded retrograde transvenous obliteration of gastric varices and aggravation of esophageal varices. Cardiovasc Intervent Radiol 2009; 32(6): 1209–1216. [DOI] [PubMed] [Google Scholar]
• 10. Uehara H, Akahoshi T, Tomikawa M, et al. Prediction of improved liver function after balloon-occluded retrograde transvenous obliteration: relation to hepatic vein pressure gradient. J Gastroenterol Hepatol 2012; 27(1): 137–141. [DOI] [PubMed] [Google Scholar]
• 11. Park JW, Yoo JJ, Kim SG, et al. Change in portal pressure and clinical outcome in cirrhotic patients with gastric varices after plug-assisted retrograde transvenous obliteration. Gut Liver 2020; 14(6): 783–791. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 12. Bewick V, Cheek L, Ball J. Statistics review 14: logistic regression. Crit Care 2005; 9(1): 112–118. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 13. Nardelli S, Riggio O, Gioia S, et al. Spontaneous porto-systemic shunts in liver cirrhosis: clinical and therapeutical aspects. World J Gastroenterol 2020; 26(15): 1726–1732. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 14. Rajesh S, Philips CA, Ahamed R, et al. Friend or foe? Spontaneous portosystemic shunts in cirrhosis-current understanding and future prospects. Can J Gastroenterol Hepatol 2021; 2021: 8795115. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 15. Bochnakova T. Hepatic venous pressure gradient. Clin Liver Dis (Hoboken) 2021; 17(3): 144–148. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 16. Jang SY, Kim GH, Park SY, et al. Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study. Clin Mol Hepatol 2012; 18(4): 368–374. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 17. Philips CA, Kumar L, Augustine P. Shunt occlusion for portosystemic shunt syndrome related refractory hepatic encephalopathy-a single-center experience in 21 patients from Kerala. Indian J Gastroenterol 2017; 36(5): 411–419. [DOI] [PubMed] [Google Scholar]
• 18. Privitera G, Figorilli F, Jalan R, et al. Portosystemic shunt embolization and recurrent ascites: a single-center case series. Gastroenterology 2018; 155(5): 1649–1650. [DOI] [PubMed] [Google Scholar]

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Original written by from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617273/