Prediction of Mortality and Hepatic Encephalopathy after TIPS

Prediction of Mortality and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement: Baseline and Longitudinal Body Composition Measurement

Clinical question

Are baseline and longitudinal body composition measurements predictive of mortality and hepatic encephalopathy outcomes following transjugular intrahepatic portosystemic shunt placement?

Take away point

Body composition measurements can be used for risk stratification in patients undergoing TIPS procedures; with improved prediction of mortality over MELD-Na and post-TIPS RA pressures alone.

Reference

Tisileli S. Tuifua, Baljendra Kapoor, Sasan Partovi, Shetal N. Shah, Jennifer A. Bullen, Jacob Enders, Sobia Laique, Abraham Levitin, Sameer Gadani, Prediction of Mortality and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement: Baseline and Longitudinal Body Composition Measurement, Journal of Vascular and Interventional Radiology, Volume 35, Issue 5, 2024, Pages 648-657.e1, ISSN 1051-0443, https://doi.org/10.1016/j.jvir.2024.01.012. (https://www.sciencedirect.com/science/article/pii/S1051044324000253)

Click here for abstract.

Study design

Retrospective case control study with Cox proportional hazard model analysis of 280 cirrhotic patients with CT scans performed 1 month prior to and 3 months status post TIPS (n = 34) from 1995-2020.

Funding Source

Not explicitly mentioned.

Setting

Academic setting, Cleveland Clinic Foundation.

Figure

Representative segmental examples of body composition measurements obtained at the level of L3 in a 66-year-old cirrhotic male. Subcutaneous adipose tissue (mSAT) in blue (a), macroscopic visceral adipose tissue (mVAT) in green (b), and core muscle area (CMA) in orange (c)

Summary

The quantity and quality of muscle and adipose tissues are known to be associated with mortality and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt placement (TIPS). However, the timing of body composition measurements remains undetermined, and the additive utility of these measures compared to the Model for End-stage Liver Disease (MELD) score alone remains unknown.

To better delineate the temporal relationship and investigate the association between body composition measurements and outcomes following transjugular intrahepatic portosystemic shunt placement, researchers performed Cox proportional hazard model analysis of TIPS registry data obtained from cirrhotic patients who had CT scans performed 2-6 weeks prior to and within 8-12 weeks status post TIPS. Multiple body composition measurements, including core muscle area and macroscopic subcutaneous adipose tissue were assessed against mortality and hepatic encephalopathy after TIPS.

Results demonstrated that higher baseline core muscle area, interval increases in core muscle area, and interval decreases in muscle adiposity index were associated with decreased mortality. Increases in macroscopic subcutaneous adipose tissue area following TIPS were associated with improved survival and yet increased risks of hepatic encephalopathy. In plain language, for every 10 cm2 decrease in core muscle area at base line, risk of death or hepatic encelphalopathy any time after TIPS placement was 18% higher for either outcome. A 10 cm2 increase in core muscle area 3-months after TIPS placement, was associated with 40% decreased risk of death any time after TIPS placement.

These findings underscore the potential utility of body composition measures in risk stratification and intervention planning for patients undergoing TIPS procedures.

Commentary

This retrospective case control study with Cox proportional hazard model analysis of 280 cirrhotic patients including 34 patients with available post-TIPS imaging preliminarily addresses a clinically relevant question about the timing and multidisciplinary utility of body composition measurements after TIPS placement. Specifically, baseline core muscle area 2-6 weeks prior to TIPS and interval changes in core muscle area 8-12 weeks after TIPS may serve as predictor or risk stratifier of mortality after TIPS placement, independent of Model for End-stage Liver Disease – Sodium modification score and post-TIPS right atrial pressure. These results encourage clinicians to have increased awareness of post-procedural complications of TIPS and preemptively initiate or modify medical management, especially in patients with sarcopenia. The current research augments prior information and the statistical methods are appropriate for analyzing the collected data. However, the small sample size in addition to the possibility of introducing selection bias due to the retrospective nature of the study may limit result strength. Future studies with larger sample sizes, prospective designs which account for confounders such as comorbid conditions and nutritional status, as well as the inclusion of other markers of liver disease severity may build upon this research. Lastly, there remains a need for basic science research to elucidate underlying the pathophysiological mechanisms. The journey is arduous, but with each study examining the causal relationship among body composition, nutritional status, and overall survival after TIPS placement, we are one step closer to individualized care in this ever-growing population of patients with liver disease.

Post Author

Ryan R. Babayev, MD, MSc
Diagnostic Radiology Resident, PGY3/R2
Hartford Hospital
@RyanBabayevMD

Preventing Type II Endoleak in Endovascular Aneurysm Repair: The Role of nBCA Injection

Injection n-Butyl-2-Cyanoacrylate into Abdominal Aortic Aneurysm Sac during Endovascular Aortic Repair prevent Type II Endoleaks Caused by Lumbar Arteries

Clinical question

Can the occlusion of target lumbar arteries using n-butyl-2-cyanoacrylate (nBCA) injection during endovascular aneurysm repair (EVAR) reduce the incidence of Type II endoleak (T2EL) after EVAR?

Take away point

Concomitant nBCA injection during EVAR significantly reduces the incidence of T2EL, offering a simple yet effective strategy to reduce T2EL incidence and improve long-term outcomes in treating AAA.

Reference

Miura S, Kurimoto Y, Maruyama R, et al. Injection of n-Butyl-2-Cyanoacrylate into the Abdominal Aortic Aneurysm Sac during Endovascular Aortic Repair to Prevent Type II Endoleaks Caused by Lumbar Arteries. J Vasc Interv Radiol. 2024;35(5):676-686. doi:10.1016/j.jvir.2023.12.573

Click here for abstract

Study design

Retrospective, non-randomized, single-center, observational cohort study

Funding Source

None

Setting

Academic setting

Figure

Figure 2. Concomitant n-butyl-2-cyanoacrylate (nBCA) injection during endovascular aneurysm repair. (a) After coil embolization of the patent inferior mesenteric artery (star) and deployment of stent-grafts, a 5-F catheter was inserted into the abdominal aortic aneurysm (AAA) sac from the contralateral side of the femoral artery (arrowheads), and patent lumbar arteries (LAs) branching from the AAA were confirmed by digital subtraction angiography (DSA) injecting within the sac. (b) nBCA/ethiodized oil mixture was injected near origins of targeted LAs by pointing the catheter tip toward the posterior wall of the aneurysm (white dotted circle). During nBCA injection, the proximal neck was occluded by an aortic occlusion balloon (asterisk) to prevent excessive distal embolization of LAs. Limited flow into a targeted LA was observed after nBCA injection (arrow). (c) Preprocedural and postprocedural computed tomography (CT) images confirmed nBCA in a previously patent left LA (arrow).

Summary

Endovascular aneurysm repair (EVAR) offers a minimally invasive alternative to open surgical repair for abdominal aortic aneurysms (AAA). However, this efficacy may be hindered by type II endoleak, a common complication involving retrograde blood flow into the aneurysm sac from patent lumbar or inferior mesenteric arteries. There is a notable disparity in the perception of type II endoleak between Asian and Western regions. While Japan reported a type II endoleak of 29%, Western countries exhibited a lower range of 10-19%. This discrepancy may be due to differences in coagulopathy, high perioperative warfarin, or antiplatelet medication rates. Furthermore, while most type II endoleaks resolve within six months post-EVAR in Western countries, they tend to persist for longer durations in Asia. This disparity prompted this investigation aimed at devising strategies to prevent type II endoleak and improve EVAR outcomes.

This study assessed the efficacy of injecting n-butyl-2-cyanoacrylate (nBCA) into the aneurysmal sac during EVAR to embolize the target lumbar arteries as a preventive measure against type II endoleak. This study involved 187 patients undergoing EVAR for infrarenal AAA between 2013 and 2020, with 106 receiving nBCA injections and 81 undergoing standard EVAR. Patient data was collected via a comprehensive review of medical records focusing on procedural details and postoperative outcomes. Selective catheterization during EVAR was performed to administer the nBCA injections into the aneurysmal sac. A balloon occlusion to prevent nBCA spillage was utilized when necessary to ensure the precise delivery of nBCA. Additionally, coil embolization of patent inferior mesenteric arteries was performed to mitigate nBCA-related adverse events. Statistical analyses included t-tests, Fisher exact tests, and multivariate regression to identify factors associated with type II endoleak incidence. Results demonstrated a significant reduction in type II endoleak occurrence and aneurysmal diameter in patients receiving nBCA injections. 2 cases of transient lower-limb motor dysfunction (1.9%) were observed, likely due to nBCA-related ischemia of the psoas or gluteus maximus muscles rather than spinal cord injury.

The study’s clinical significance lies in the potential of nBCA injection to decrease type II endoleak incidence, preventing future repeated interventions to correct type II endoleak, and improve long-term outcomes post-EVAR. Both the simplicity and efficacy of nBCA injection make it promising. These findings also align with prior research in EVAR, contributing to the ongoing discussion regarding the influence of type II endoleak on EVAR outcomes. However, limitations such as the study’s retrospective nature and sample size were acknowledged, emphasizing the need for further research to validate findings and assess safety and cost-effectiveness of nBCA injection in EVAR procedures compared to other interventions.

Commentary

This study has addressed a major issue in the management of AAA with EVAR, namely the prevention of type II endoleak. Efficacy of nBCA into the aneurysmal sac during EVAR as a preventive measure against type II endoleak and its influence on long-term outcomes (decreased incidence of sac enlargement and reintervention) for patients with AAA was demonstrated. However, its retrospective design and limited sample size may restrict the external validity or broader applicability of these findings. Furthermore, attention should be paid to the study’s specific patient population (Japan, Asian) and practice pattern (nBCA has been categorized as reimbursable since 2023 and on-label; Onyx has not been approved). Overall, this study presents encouraging findings regarding the efficacy of nBCA injections in enhancing EVAR outcomes. But to integrate this preventive measure into clinical practice, additional information about the long-term safety, cost-effectiveness, and comparison with other preventive measures from larger prospective studies are necessary.

Post Author
Danielle Millner Balagtas, BA
MD Candidate, Class of 2027
University of Massachusetts Chan Medical School
@daniellelmb

Y90 and Immune Checkpoint Inhibitor Synergy Is the Future

Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma

Clinical question

Is combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization superior in outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC).

Take away point

 Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

Reference

Garcia-Reyes, K., Gottlieb, R. A., Menon, K. M., Bishay, V., Patel, R., Patel, R., Nowakowski, S., Sung, M. W., Marron, T. U., Gansa, W. H., Zhang, J., Raja, S. C., Shilo, D., Fischman, A., Lookstein, R., & Kim, E. (2024). Radioembolization plus immune checkpoint inhibitor therapy compared with radioembolization plus tyrosine kinase inhibitor therapy for the treatment of hepatocellular carcinoma. Journal of Vascular and Interventional Radiology.

Click here for abstract: Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma - Journal of Vascular and Interventional Radiology (jvir.org)

Study design

A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included.

Funding Source

None listed

Setting

Academic, The Mount Sinai Hospital

Figure

Summary/Commentary

In Garcia-Reyes et al. 2024’s Journal of Vascular and Interventional Radiology (JVIR) article, they provided limited retrospective evidence on the superiority of Yttrium-90 radioembolization in combination with immune checkpoint inhibitors over the combination of Yttrium-90 with Tyrosine Kinase inhibitors. In the figure above, it showed the superiority in both overall survival and progression-free survival curves for Yttrium-90 with the immune checkpoint inhibitors over the tyrosine kinase inhibitors when compared in the early time frame. This initial effect did not persist long enough to statistically affect disease progression or survival outcomes but the trend remained in favor of Yttrium-90 radioembolization and immune checkpoint inhibitors combination therapy. The main statistically significant finding was improved imaging responses. Yttrium-90 plus immune checkpoint inhibitor combination therapy also caused significantly fewer regimen-modifying adverse effects than Yttrium-90 plus tyrosine kinase inhibitor treatment and significantly fewer overall adverse events. 63.2% of patients in the yttrium-90 plus tyrosine kinase inhibitor group terminated systemic therapy owing to adverse effects, which was significantly higher than the 5.3% in the yttrium-90 plus immune checkpoint inhibitor group. Such improved treatment adherence and quality of life of patients undergoing combination therapy for advanced hepatocellular carcinoma will be the focus of ongoing and future clinical trials, in addition to progression free and overall survival.

The pathophysiology behind the combination therapy is intriguing, that the “locoregional therapies including ablation, transarterial chemoembolization, and yttrium-90 radioembolization may help prime the immune system and improve the effectiveness of immune checkpoint inhibitor therapies in the treatment of unresectable Hepatocellular Carcinoma.” This theory was supported by Craciun et al. who found an increase in granzyme B+ lymphocytes in the tumor as well as higher numbers of CD4 and CD8+ T cells in resected tissue after radioembolization compared to those found in patients who underwent chemoembolization or no pre-resection treatment. As there are additional studies on yttrium-90 in combination with other immune checkpoint inhibitors (i.e. yttrium-90 before durvalumab plus tremelimumab (ROWAN, NCT05063565)), the synergistic effects between radioembolization and immune checkpoint inhibitors will be further delineated. The idea that the destruction of the cancer cell induced by the radioembolization results in recruitment of immune cells to the tumor microenvironment as well as enhancing tumor immunogenicity (through increasing tumor antigen release) is profound. The promising results so far may prompt new guidelines in favor of the combination of yttrium-90 and immune checkpoint inhibitors. Furthermore, advances in the context of advanced hepatocellular carcinoma open the possibility of applying the concept of radioembolization with immune checkpoint inhibitors to other malignancies as well.

Post Author

Tony Nguyen

PGY-1

Integrated Interventional Radiology Resident

UMass Chan Medical School