Portal Vein Thrombosis After Transarterial Embolization for Hepatocellular Carcinoma

Abstract

This cross-sectional study assesses the association between venous thrombosis and embolization in patients with hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is recommended for patients with asymptomatic, large, or multifocal hepatocellular carcinoma (HCC) without extrahepatic metastases.¹ Transarterial chemoembolization combines targeted chemotherapy, often with Lipiodol, with embolization of the tumor’s blood supply.² Known risks of TACE include biliary (stricture and leak) and hepatic artery (stenosis and thrombosis) complications.² Little is known about venous thrombosis (VT) after locoregional therapies, which has been described after microwave and radiofrequency ablation (RFA). This study sought to describe the incidence and natural history of portal vein thrombosis (PVT) after TACE.

Methods

This retrospective cross-sectional study analyzed records of patients who underwent TACE and/or transarterial bland embolization to treat HCC at San Francisco Veteran Affairs (SFVA) Medical Center from 2003 to 2011 and 2015 to 2017. These dates were from SFVA Department of Hepatology’s databases.³ The SFVA Institutional Review Board approved this study and waived the informed consent requirement because deidentified data were used. We followed the STROBE reporting guideline and the Declaration of Helsinki.⁴

We collected demographic, disease, and procedural characteristics and PVT details. Patients underwent imaging within 6 months after TACE. The primary outcome was presence of new VT after embolization on the imaging report (read by in-house radiologists). The eMethods in Supplement 2 describe the embolization technique. Data analysis was performed between October 2022 and March 2023, using Microsoft Excel version 16 (Microsoft Corp).

Results

We included 124 male veterans (mean [SD] age, 61 [8] years. Eighty-one patients (65%) had cirrhosis, with 51 (41%) having Child-Pugh B and 3 (2%) having Child-Pugh C cirrhosis. The number of tumors ranged between 1 and 5. Seventy-five patients (60%) underwent 1 TACE procedure, 36 (29%) underwent 2, and 13 (11%) underwent 3 to 4 procedures. Follow-up ranged from 6 months to 17 years.

On postprocedure imaging, 12 patients (10%) had a new PVT, 15 (12%) had unchanged thrombosis, 85 (69%) had no thrombosis, and 12 (10%) did not have imaging that could be evaluated for thrombosis. Thrombosis ranged from a posterior branch of the right portal vein to complete thrombosis of the right and left portal vein. No patient received anticoagulation, and none appeared to have clinically significant sequelae (no pulmonary embolism).

One patient underwent a single TACE for HCC tumor and developed progressive biliary necrosis and portal vein occlusion over 8 months (Figure 1). The patient received no anticoagulant for these imaging findings. Another example is described in Figure 2.

Figure 1. Development of Right Hepatic Vein Thrombosis After Transarterial Chemoembolization.

A-F, Imaging depicts the development of right hepatic vein thrombosis. C, Arrowhead points to necrosis. D, Arrowhead points to thrombosis. E, Arrowhead points to biliary necrosis. After hypertrophy of the left liver remnant, the patient underwent left hepatectomy. TACE indicates transarterial chemoembolization.

Figure 2. Development of Portal Vein Thrombosis and Atrophy Hypertrophy Complex After Transarterial Chemoembolization.

A-F, Imaging depicts portal venous thrombosis and atrophy hypertrophy complex. Arrowheads in panels C, E, and F point to portal vein thrombosis. The patient did not undergo surgical resection. TACE indicates transarterial chemoembolization.

Discussion

Ten percent of patients developed new PVT. An RFA case series described a 1.4% rate of hepatic VT and a 1.7% rate of PVT.⁵ The incidence rate in this study was higher, suggesting an association of chemotherapy and embolic particles in TACE with increased thrombosis compared with microwave ablation or RFA.

No patient required anticoagulation or systemic therapy. Liver function test results were normal. Since many patients undergo more than 1 TACE (in this study, 49 of 124 underwent ≥2 embolizations) and findings suggest that portal vein thrombus can be seen after TACE, with negligible implications for patients’ clinical course, it raises the question of whether portal vein thrombus should be considered as a true contraindication.⁶ The pathophysiological process behind this procedural sequela remains unexplained. We hypothesized that biliary epithelium, which is dependent on arterial blood flow, becomes ischemic and a factor in ballooning, as seen in Figure 1. The portal triad is encased by the Glisson fibrous sheath and is a confined compartment. We believe the necrotic, dilated bile ducts expand and compress the associated low-pressure portal venous branches, and ultimately thrombosis develops.

Study limitations include the single-center retrospective design with an all-male population and the lack of long-term follow-up. Nevertheless, this descriptive study is important for clinicians caring for patients with HCC. The World Health Organization estimates 1 million annual deaths from HCC by 2030⁶; locoregional therapies will continue to grow. Understanding the possible sequelae, including PVT, and how they may affect other future therapies, especially surgery, is crucial.

Supplement 1.

eMethods. Description of Embolization Technique

Supplement 2.

Data Sharing Statement