Effect of transjugular intrahepatic portosystemic shunt on platelet count and exact spleen volume segmented on computed tomography

Abstract

Background

Transjugular intrahepatic portosystemic shunt (TIPS) is effective for portal decompression, but its effect on splenic congestion is not proven. Platelet changes and spleen size following TIPS are controversially reported while the exact volume of the spleen has rarely been investigated.

Purpose

To analyze the effect of TIPS placement on portosystemic gradient (PSG), platelet count (PLT), and exact spleen volume (SV) using contrast-enhanced computed tomography (CT).

Methods

For study inclusion, successful TIPS placements in adult patients with liver cirrhosis and portal hypertension who received CT within 3 months prior and 12 months after TIPS-placement were reviewed (12/2013–09/2021). Exclusion criteria were additional liver/portal interventions, TIPS-dysfunction, progressive portal/liver vein occlusion and hepatic malperfusion or progressive portosystemic collaterals, and active bleeding on CT. Additionally, patients with splenic/hematological disorders, hemodialysis, and clinical apparent infections/multi-organ-failure/death were excluded. PSG and PLT were recorded. Exact SV were segmented on pre-/post-TIPS-CT. Data were compared before and after TIPS placement. Mean ± standard deviation and significance level (p) were given.

Results

Overall, data of 18 TIPS procedures were available for comparison. PSG reduction following TIPS placement was significant (pre: 18 ± 7 mmHg, post: 5 ± 2 mmHg; p < .001). SV tended to decrease (pre: 832 ± 412 cm³, post: 772 ± 345 cm³; p = .112) and PLT did not change (pre: 130 ± 64Tsd/µL, post: 116 ± 61Tsd/µL; p = .160).

Conclusion

When exact SV is assessed and confounders are excluded using CT, neither a significant SV reduction nor a PLT-increase are detected following TIPS. Patients without PLT increase and SV reduction after TIPS might benefit from additional interventions (e.g., splenic artery embolization).

Keywords

TIPS portal hypertension spleen platelet hypersplenism segmentation

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention to reduce the portosystemic gradient (PSG) in patients with therapy refractory portal hypertension.¹ In these patients, splenic congestion might be a relevant cause of thrombocytopenia due to increased pooling of platelets in an enlarged spleen,² and this can predispose the risk for severe bleeding.³ Although an increase in platelet count (PLT) and decrease in spleen volume (SV) have been confirmed in patients with liver cirrhosis within 1 or 2 months after orthotopic liver transplantation,⁴ the effect of TIPS placement is controversially discussed.^5–14 Of note, the exact SV in patients with liver cirrhosis and portal hypertension undergoing TIPS placement has been reported in a single study to date.¹⁰ Moreover, potential confounders for SV and PLT, partly discussed in the literature,^11,13–15 have not consistently been excluded in prior studies, for example, platelet transfusion, clinical apparent infections, hematological disorders, hepatic malperfusion, new portal vein thrombosis, or portosystemic collateral pathways following TIPS placement.^5–8,10,11 Therefore, we aim to evaluate the effect of TIPS placement on PSG, PLT, and SV using dedicated inclusion and exclusion criteria and contrast-enhanced computed tomography (CT) with total spleen volumetry in patients with liver cirrhosis and portal hypertension.¹⁶

Methods

Study population

Overall, 364 TIPS procedures were performed in our tertiary center (12/2013–09/2021). Cross-sectional imaging of the patients was routinely reviewed TIPS evaluation. After TIPS placement, ultrasound imaging was performed for follow-up. Cross-sectional imaging was only performed after TIPS procedures, if follow-up examinations revealed abnormal findings or for different indications. Dedicated inclusion and exclusion criteria were applied to exclude potential confounders (Table 1). Patient characteristics were recorded including age, gender, primary liver disease, presence of malignancy, and model end-stage of the liver disease (MELD). Informed consent was obtained from all individual participants included in the study. Institutional review board approval from the local ethics committee of Hannover Medical School was obtained (MHH Ethikkommission, Nr. 9753_BO_K_2021, 05/05/2021).

Table 1.

Study inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
• Patient age ≥18 years	• Patient age <18 years (n = 7)
• Successful standard TIPS placement	• Unsuccessful or a different TIPS procedure (n = 12 and n = 16)
• Presence of liver cirrhosis and portal hypertension with refractory ascites or variceal bleeding	• No liver cirrhosis and portal hypertension with refractory ascites or variceal bleeding (n = 0)
• Available contrast-enhanced CT within 3 months prior to TIPS placement	• No available contrast-enhanced CT within 3 months prior to TIPS placement and 12 months after TIPS placement (n = 253)
• Available contrast-enhanced CT within 12 months after TIPS placement	• Additional liver or portal interventions after TIPS placement and before post-TIPS-CT (n = 14)
	• TIPS-occlusion/-stenosis/-dysfunction (n = 14)
	• Splenic lesions or spleen not completely depicted on field-of-view (n = 6)
	• New/progressive main portal vein thrombosis, new intrahepatic portal vein/liver vein occlusion and hepatic malperfusion or ischemia or infarct/acute liver failure or new/progressive portosystemic collaterals on CT (n = 9)
	• Active bleeding with active contrast extravasation on CT (n = 0)
	• Clinical apparent infections (diagnosis in medical reports/focus of infection and elevated C-reactive protein), sepsis, multi-organ-failure/death (n = 9)
	• Hematological disorders (n = 2)
	• Hemodialysis (n = 1)
	• Platelet transfusion <8 days before blood sampling (n = 1)
	• Inadequate data (n = 2)

In this table, the dedicated inclusion and exclusion criteria are given. Abbreviations: CT: computed tomography; n: number; PLT: platelet count; TIPS: transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt

All TIPS placements were performed by experienced interventional radiologists on angiography systems (MultiDIAGNOST4, Philips Healthcare, Netherlands; Siemens Artis Q^®/ Pheno^®, Siemens Healthcare, Germany) under general anesthesia. TIPS procedures were conducted using specific TIPS set (GORE TIPS Set, AZ, USA) and TIPS endoprosthesis (Viatorr, Gore, AZ, USA).¹⁶ The diameter of TIPS endoprosthesis was set to 8 mm and dilated as needed to reduce PSG >50% or ≤12 mmHg.¹ In 2 cases, a constrained TIPS with a diameter of 6 mm was established.¹⁷ If necessary, embolization of portosystemic shunts/esophagogastric varices (VE) was performed. Procedural characteristics were assessed and included TIPS indication, CT indication, TIPS diameters, additional VE, and time intervals between PLT, CT imaging, and TIPS placement.

Portosystemic gradient, platelet count, and spleen volume

The pressure in the inferior cava vein and portal vein was measured before and after TIPS placement. PSG were calculated. Standard PLT analyses were performed in anticoagulated venous blood samples before and after TIPS placement at the time of CT. SV was assessed via manual segmentation using freehand 3D region of interest tools of Visage 7 (VISAGE Imaging, Pro Medicus Inc., VIC, AU) on contrast-enhanced CT images generated on multi-slice CT (Lightspeed/ Lightspeed VCT, GE Healthcare, Chalfont St. Giles, UK; SOMATOM Force, Siemens Healthineers, Erlangen, GER; Aquilion ONE, Canon Medical Systems Corporation, Otawara, Japan) before and after TIPS placement.

Statistical analysis

PSG, PLT, and SV were compared pre- and post-TIPS. Comparisons of data were performed two-sided with paired Student’s t-Test or Wilcoxon-Test according Shapiro–Wilk test. Values were given as mean (± standard deviation). Significance level was p < .05. Statistical analysis was performed using SPSS (IBM SPSS Statistics 29, IBM, NY, USA).

Results

Patient and procedural characteristics

Overall, 18 patients with available contrast-enhanced CT before and after TIPS placement were included. Patients were predominantly male (77%) with a mean age of 58 years and had most common an ethyl-toxic liver disease (38%). Malignancy was present in five patients (27%). Mean MELD was 10 before TIPS placement. The mean interval between PLT and CT before TIPS placement was 1 day, and the mean interval between PLT and CT after TIPS placement was also 1 day. Mean intervals between CT and TIPS placement and between TIPS placement and post-TIPS-CT were 19 days and 62 days, respectively. Main indication for pre-TIPS-CT was TIPS evaluation (94%) and for TIPS placement it was refractory ascites (72%). CT imaging after TIPS placement was common an emergent indication (55%). Additional VE was performed in a few patients (33%). Results are given in Tables 1 and 2.

Table 2.

Patient and procedural characteristics.

Patient characteristics
Age (years)	58 ± 12
Gender (male/female)	14/4
Liver disease (ethyl-toxic/other)	7/11
Malignancy (none/present)	13/5
MELD	10 ± 3

Procedural characteristics
Time between PLT and CT before TIPS (days)	1 ± 1
Time between PLT and CT after TIPS (days)	1 ± 1
Time between pre-TIPS-CT and TIPS (days)	19 ± 18
Time between TIPS and post-TIPS-CT (days)	62 ± 74
Indication for pre-TIPS-CT (evaluation/other)	17/1^a
TIPS-indication (ref. ascites^b/ref. bleeding)	13/5
Indication for post-TIPS-CT (non-emergency/emergency/emergency bleeding)	8/5/5
Diameter of TIPS stent (6 mm/8 mm/10 mm)	2/13/3
Additional procedures (VE/none)	6/12

In this table, patient and procedural characteristics are given. Abbreviations: CT: computed tomography; MELD: model of end-stage liver disease; PLT: platelet count; TIPS: transjugular intrahepatic portosystemic shunt; VE: variceal embolization.

^aThe indication for pre-TIPS-CT was tumor staging in one patient.

^bRefractory ascites compromises also refractory hydropic decompensation, hepatorenal syndrome, or hepatopulmonary syndrome. In contrast, ref. bleeding compromises recurrent or uncontrollable gastrointestinal/variceal bleeding.

Portosystemic gradient, platelet count, and spleen volume

Technical success was achieved in all patients with significant PSG reduction from pre-TIPS-PSG of 18 ± 7 mmHg to post-TIPS-PSG of 5 ± 2 mmHg (p < .001). Pre- and post-TIPS-PLT were not significantly different with 130 ± 64Tsd/µL and 116 ± 61Tsd/µL (p = .160), respectively. Further, SV before TIPS placement was 832 ± 412 cm³ and SV after TIPS placement was 772 ± 345 cm³ (p = .112). Details are given in Figure. 1.

Figure 1.

Results of portosystemic gradient, platelet count, and spleen volume. This figure illustrates the results of the portosystemic gradient, platelet count, and spleen volume before and after transjugular intrahepatic portosystemic shunt placement. Mean and standard deviation of the study cohort are displayed for portosystemic gradient, platelet count, and spleen volume in A, B, and C, respectively. Individual data are visualized for portosystemic gradient, platelet count, and spleen volume in D, E, and F, respectively. Abbreviations: PLT = platelet count; post = post-interventional; pre = pre-interventional; PSG = portosystemic gradient; SV = spleen volume.

Discussion

Reviewing our results, we find no significant changes in SV and PLT in our study cohort after TIPS placement, although significant PSG reduction was achieved in all patients. In the majority of prior studies, PLT significantly increases in patients after TIPS placement.^{8–10,12–14} However, some studies have reported no significant PLT increase after TIPS placement.^5–7,11 The spleen size in patients after TIPS placement has been investigated in four studies, and it has not decreased in two of these studies.^9,10,12,13 Thereof, exact SV has only been analyzed in a single study before with a moderate SV reduction of 20%.¹⁰ Moreover, several of these studies have reported neither exclusion of potential confounders^6–8,10,11 nor imaging to control TIPS patency (e.g., ultrasound and cross-sectional imaging).^8,11,12 Interestingly, our study confirms the absence of PLT increase and SV reduction reported in recent studies with 601 and 192 patients by Wong et al. and Bucsics et al., respectively, which neither segmented exact SV nor considered the aforementioned confounders.^5–14

In detail, the mean PLT values of our cohort before and after TIPS placement are slightly below the threshold for thrombocytopenia (<150Tsd/µL).³ Of note, mean PLT in our study is lower after than before TIPS-placement, which has been observed before, and potential liver function impairment is discussed.^5,14 In contrast, the mean SV of 832 cm³ is clearly increased at baseline compared to the mean SV of 214 cm³ of healthy individuals.¹⁸ Nevertheless, there is also no significant SV reduction (ca. −4%) after TIPS placement in our cohort. This absence of SV reduction might be caused by secondary splenic fibrosis in patients with a long history of liver cirrhosis and portal hypertension as shown in an animal model.¹⁹ Overall, the combination of mild thrombocytopenia before TIPS placement and the lack of PLT increase and SV reduction after TIPS placement implies no severe portalvenous congestion of the spleen in our patients. Recently, Gemery et al.²⁰ discussed factors regarding hematologic production, for example, thrombopoietin production, that might not be influenced by TIPS placement. Accordingly, orthotopic liver transplantation, which erases portal congestion and restores normal liver function (including thrombopoietin production), leads immediately to significant SV reduction and PLT increase.^4,21 TIPS placement’s effect on both portal congestion and liver function seems limited, particularly without immediate and relevant SV reduction and PLT increase. If severe thrombocytopenia (<50Tsd/µL) and relevant bleeding risk persist in patients after TIPS placement,³ spleen embolization might be an option to reduce SV, increase PLT, and improve bleeding risk.²²

Our study cohort differs from prior studies and has several limitations.^5–14 Since patients do not receive CT by standard after TIPS placement, our study cohort is limited. In addition, CT imaging after TIPS placement is only available with a mean interval of around 2 months and a wide range, and more than half of the patients having an emergent indication. Further, subtle platelet consumption cannot be completely ruled out, although patients with platelet transfusion and active bleeding on CT were not included. Finally, decreased hematologic production, especially induced by medication, could not be excluded since these data were not available.

In conclusion, neither SV- nor PLT changes are significant following TIPS when CT images are analyzed and several confounders are excluded. Furthermore, this short report highlights the value of cross-sectional imaging for accurate assessment of spleen size and portal hemodynamics.

Footnotes

Acknowledgments

We thank the Enterprise Research Data Warehouse and the Center for Laboratory Medicine for the data provision at the Hannover Medical School. This study was supported by PRACTIS Clinician Scientist Program, funded by Hannover Medical School and DFG (DFG ME 3696/3) – T.C.M.

Author contributions

Surgical and medical practices: B.M., J.B.H., B.C.M., F.K.W., and T.C.M. Concept: B.M., J.B.H., F.K.W., and T.C.M. Design: S.S.Y., B.M., J.B.H., B.C.M., F.K.W., and T.C.M. Data collection of processing: S.S.Y. and T.C.M. Analysis or interpretation: S.S.Y., B.M., J.B.H., B.C.M., F.K.W., and T.C.M. Literature search: S.S.Y., J.B.H., and T.C.M. Writing: S.S.Y., B.M., J.B.H., B.C.M., F.K.W., and T.C.M.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors of this manuscript declare relationships with the following companies: Siemens Healthcare and ProMedicus (B.C.M. and F. K. W. outside the submitted work) and Delcath Systems Inc (F.K.W. outside the submitted work). The remaining authors declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by PRACTIS Clinician Scientist Program, funded by Hannover Medical School and DFG (DFG ME 3696/3) – T.C.M.

Ethical consideration

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Consent for publication was obtained for every individual person’s data included in the study.

IRB approval

This study has obtained IRB approval from the local ethics committee of Hannover Medical School (MHH Ethikkommission, Nr. 9753_BO_K_2021, 05/05/2021).

Dual publication

A preliminary data analysis was presented at the CIRSE Annual Congress and published in the CIRSE Book of Abstracts in 2022.

ORCID iD

Timo C. Meine

Data Availability Statement

The datasets generated and/or analyzed during the current study are not publicly available due to data protection regulations but may be available under certain legal requirements upon reasonable request.*

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