Role of Interventional Radiology in Hepatocellular Carcinoma: Transarterial Chemoembolisation and Beyond

Introduction

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and represents a significant global health challenge, ranking among the leading causes of cancer-related mortality worldwide. Its incidence continues to rise due to the increasing prevalence of chronic liver diseases, particularly cirrhosis, chronic infection with hepatitis B and C viruses, alcohol-related liver disease, and non-alcoholic fatty liver disease. The pathogenesis of HCC is complex and multifactorial, involving chronic inflammation, hepatocellular injury, fibrosis, and progressive genetic and epigenetic alterations that ultimately lead to malignant transformation. 

Early-stage HCC is often asymptomatic, and despite improvements in surveillance strategies, many patients are diagnosed at an intermediate or advanced stage. This delayed presentation significantly limits the applicability of curative treatment options such as surgical resection, liver transplantation, and local ablative therapies. Moreover, underlying liver dysfunction and comorbidities further restrict treatment eligibility, making management particularly challenging. In this setting, the need for effective, minimally invasive, and patient-tailored therapeutic approaches becomes increasingly critical.

Interventional radiology (IR) has emerged as a cornerstone in the multidisciplinary management of HCC, bridging the gap between diagnostic imaging and therapeutic intervention. By utilising advanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound, IR enables precise localisation and targeted treatment of hepatic lesions. Among these techniques, transarterial chemoembolisation (TACE) has become the standard of care for patients with intermediate-stage disease, particularly those classified under the Barcelona Clinic Liver Cancer staging system. TACE exploits the dual blood supply of the liver by selectively delivering chemotherapeutic agents into the tumour-feeding hepatic arteries, followed by embolisation to induce ischaemic necrosis, thereby maximising tumour control while preserving the surrounding liver parenchyma. 2,3

Recent technological advancements are driving a paradigm shift towards precision and personalised medicine in interventional oncology. The incorporation of robotic-assisted systems enhances procedural accuracy and operator control, while three-dimensional (3D)-printed patient-specific models facilitate pre- procedural planning and device customisation. Furthermore, the development of smart implants with embedded biosensors enables real-time monitoring of treatment response and early detection of complications, thereby optimising clinical outcomes. The integration of artificial intelligence (AI) into radiological workflows further augments diagnostic accuracy, treatment planning, and outcome prediction, reinforcing the role of IR as a dynamic and evolving speciality. 4-7

Pathophysiology and Imaging Basis

HCC exhibits unique vascular and biological characteristics that form the foundation for both its radiological diagnosis and interventional management. One of the most critical features of HCC is its predominant arterial blood supply, in contrast to normal liver parenchyma, which derives approximately 70%–80% of its blood flow from the portal vein and only 20%–30% from the hepatic artery. This fundamental difference in vascularisation plays a pivotal role in the development, progression, imaging appearance, and treatment of HCC. 2,3

Tumour angiogenesis and vascular remodelling

The pathogenesis of HCC involves progressive angiogenesis driven by chronic liver injury and inflammation. During hepatocarcinogenesis, there is a shift from portal venous perfusion to arterial neoangiogenesis, mediated by pro-angiogenic factors such as vascular endothelial growth factor. As the tumour grows, it develops an abnormal network of unpaired arteries, reduced portal venous supply, and sinusoidal capillarisation. These vascular changes result in:

• Increased arterial perfusion
• Decreased portal venous contribution

• Formation of tortuous, irregular tumour vessels

  This altered haemodynamic profile is a hallmark of HCC and serves as the basis for both imaging diagnosis and targeted intra-arterial therapies. 2,3 

Imaging characteristics of HCC

The vascular behaviour of HCC is reflected in its characteristic appearance on contrast-enhanced imaging modalities, particularly CT and MRI. 

Arterial phase hyperenhancement

During the arterial phase, HCC lesions demonstrate intense enhancement due to their rich arterial supply. This feature is highly sensitive for detecting hypervascular tumours.

Portal venous and delayed phase washout 

In the portal venous and delayed phases, HCC lesions typically exhibit washout, appearing hypodense or hypointense relative to the surrounding liver parenchyma. This occurs because the tumour lacks normal portal venous perfusion, while the background liver enhances.

Capsule appearance

A peripheral enhancing capsule may be observed in delayed phases, representing a fibrous pseudocapsule surrounding the tumour.

Diffusion and hepatobiliary imaging

On MRI, diffusion-weighted imaging (DWI) shows restricted diffusion in HCC due to high cellularity. Hepatobiliary contrast agents further improve lesion detection by demonstrating reduced uptake in tumour tissue compared to normal hepatocytes.

These imaging features form the cornerstone of non-invasive diagnosis, often eliminating the need for a biopsy.2,3

Physiological Basis for Intra-Arterial Therapies

The preferential arterial supply of HCC provides a unique therapeutic advantage that is exploited in interventional radiology. Procedures such as TACE and transarterial radioembolisation selectively target tumour-feeding arteries while sparing the surrounding normal liver tissue, which continues to receive blood from the portal vein. 2,3

Clinical Implications

Understanding the vascular biology of HCC is essential for:

• Accurate radiological diagnosis
• Treatment planning and patient selection
• Predicting response to therapy
• Monitoring post-treatment outcomes

Furthermore, variations in tumour vascularity may influence therapeutic response, with hypervascular tumours generally responding better to intra-arterial therapies. 2,3

Transarterial Chemoembolisation

TACE is a cornerstone locoregional therapy in the management of HCC, particularly for patients with intermediate-stage disease who are not candidates for curative treatments such as surgical resection or liver transplantation. It is a minimally invasive, image-guided procedure that combines targeted chemotherapy delivery with arterial embolisation to achieve selective tumour necrosis while preserving the surrounding liver tissue. 2,3,8

Principle and mechanism of action

The therapeutic efficacy of TACE is based on the unique vascular supply of HCC, which is predominantly arterial. The procedure involves two synergistic mechanisms:

• Targeted chemotherapy delivery: High concentrations of chemotherapeutic agents are directly infused into the tumour-feeding hepatic arteries, maximising local cytotoxic effects while minimising systemic exposure.
• Arterial embolisation: Embolic agents are subsequently administered to occlude the arterial blood supply, leading to ischaemia and prolonged retention of the chemotherapeutic drugs within the tumour.

This combined approach results in tumour ischaemia, hypoxia, and enhanced drug-induced cytotoxicity, ultimately leading to tumour necrosis. 2,3

Procedural technique

TACE is typically performed under fluoroscopic guidance in an interventional radiology suite using a stepwise approach: 2,3

Vascular access

• Percutaneous access is usually obtained via the common femoral artery (or radial access in selected cases).
• A vascular sheath is inserted to facilitate catheter manipulation.

Diagnostic angiography

• A catheter is advanced into the oceliac trunk and common hepatic artery.
• Angiographic imaging is performed to delineate hepatic arterial anatomy and identify tumour- feeding vessels.
• Variants such as replaced or accessory hepatic arteries are carefully assessed.

Superselective catheterisation

• A microcatheter is navigated into the segmental or subsegmental arteries supplying the tumour.
• Superselective delivery improves treatment efficacy and reduces damage to normal liver tissue.

Drug delivery

• Chemotherapeutic agents (e.g., doxorubicin, cisplatin, or epirubicin) are infused directly into the tumour vasculature.
• In conventional TACE, these drugs are often mixed with lipiodol, an oily contrast agent that enhances drug retention within the tumour.

Embolisation

• Embolic materials (e.g., gelatin sponge particles, polyvinyl alcohol particles, or microspheres) are injected to occlude arterial flow.
• This results in vascular stasis and promotes ischaemic necrosis. 2,3

Precision and Personalised Interventional Radiology

The field of IR has undergone a significant transformation from a primarily technique-based speciality to a precision-driven and patient-centred discipline. In the management of HCC, this evolution is particularly evident, as treatment strategies are increasingly tailored to individual patient anatomy, tumour characteristics, and underlying liver function. Advances in technology have enabled a more refined and targeted therapeutic approach, thereby improving both efficacy and safety. 2,3

One of the most notable developments is the integration of robotic-assisted surgery, which enhances procedural precision and reproducibility. Robotic systems facilitate accurate catheter navigation within the complex hepatic arterial network, allowing for superselective targeting of tumour-feeding vessels. This not only improves therapeutic outcomes but also minimises damage to the surrounding healthy liver parenchyma. Additionally, robotic assistance reduces operator fatigue and radiation exposure, contributing to overall procedural efficiency and safety. 2,3

Another major advancement is the application of 3D printing in medicine, which enables the creation of patient-specific anatomical models based on high- resolution imaging data. These models provide a 3D understanding of tumour location and vascular anatomy, allowing for detailed pre-procedural planning and simulation. In complex cases of HCC, 3D printing enhances the accuracy of catheter placement and ablation techniques, thereby reducing intra-procedural uncertainty and improving clinical outcomes. 2,3

Furthermore, the emergence of smart implants has introduced the possibility of real-time monitoring in interventional oncology. These implants incorporate biosensors capable of tracking physiological parameters such as temperature, pressure, and biochemical changes within the tumour microenvironment. Such real-time data can facilitate early detection of complications, assessment of treatment response, and timely clinical decision- making. Collectively, these innovations are redefining IR as a highly personalised and precision-oriented speciality. 9-13

Role of Artificial Intelligence 

AI is increasingly being integrated into interventional radiology, playing a transformative role in enhancing diagnostic accuracy, procedural planning, and therapeutic outcomes in HCC. AI-driven algorithms, particularly those based on deep learning, have demonstrated significant potential in the automated detection and segmentation of hepatic tumours on imaging modalities such as CT and MRI. This not only improves early diagnosis but also reduces interobserver variability and enhances reproducibility.

In addition to diagnostic applications, AI serves as a powerful tool for treatment planning and decision support. By analysing large datasets that include imaging features, clinical parameters, and patient outcomes, AI models can predict tumour behaviour, assess treatment response, and assist clinicians in selecting the most appropriate therapeutic approach. This is particularly valuable in complex cases where multiple treatment options are available, such as choosing between TACE, ablation, or combination therapies.

Moreover, AI has the potential to provide real-time procedural guidance during interventional procedures. Through techniques such as image fusion and augmented reality, AI can overlay pre-acquired CT or MRI data onto live fluoroscopic images, enabling precise navigation and targeting. Automated vessel tracking and catheter guidance further enhance procedural accuracy while reducing the risk of complications. Additionally, AI-based predictive models can aid in post-procedural monitoring by identifying patients at higher risk of recurrence or adverse outcomes, thereby facilitating personalised follow-up strategies. Despite these advancements, challenges such as data standardisation, regulatory concerns, and integration into clinical workflows remain to be addressed. 2,3

Complications

Although IR procedures are minimally invasive and generally well tolerated, they are not without risks, particularly in patients with underlying liver dysfunction. One of the most common complications following procedures such as TACE is post- embolisation syndrome, which is characterised by fever, abdominal pain, nausea, and malaise. This condition results from tumour necrosis and the associated inflammatory response and is typically self-limiting with supportive management.

More serious complications include hepatic decompensation and liver failure, especially in patients with advanced cirrhosis or compromised liver function. These patients may develop worsening ascites, hepatic encephalopathy, or coagulopathy following the procedure. Therefore, careful patient selection and pre-procedural assessment of liver function are essential to minimise these risks. Another significant concern is non-target embolisation, where embolic agents inadvertently occlude vessels supplying non- tumour tissues, potentially leading to complications such as gastrointestinal ischaemia, cholecystitis, or pancreatitis. The use of superselective catheterisation techniques has been instrumental in reducing the incidence of such events.

Infectious complications, including hepatic abscess formation and sepsis, may also occur, particularly in patients with biliary interventions or immunocompromised states. Additionally, vascular complications such as arterial dissection, access site haematoma, and contrast-induced nephropathy can arise during or after the procedure. Despite these potential risks, advancements in imaging guidance, procedural techniques, and supportive care have significantly improved the safety profile of interventional radiology procedures. 2,3

Future Perspectives

The future of IR in the management of HCC is poised to be shaped by continuous technological innovation and the integration of multidisciplinary approaches. One of the most promising developments is the emergence of AI-integrated interventional platforms, which combine real-time imaging, automated data analysis, and decision support systems to enhance procedural precision and efficiency. These platforms are expected to enable more accurate targeting of tumours and improve overall treatment outcomes.

Personalised dosimetry represents another advancement, particularly in therapies such as transarterial radioembolisation. By tailoring radiation doses based on tumour characteristics, vascularity, and patient-specific liver function, clinicians can optimise therapeutic efficacy while minimising toxicity. Similarly, nanotechnology-based therapies are gaining attention for their potential to deliver drugs directly to tumour cells with high specificity, thereby reducing systemic side effects and enhancing treatment response. 2,3

The integration of multimodal treatment strategies, including interventional procedures, systemic therapies, and immunotherapy, is also expected to play a crucial role in the future management of HCC. These combined approaches aim to achieve synergistic effects and improve long-term survival. Ultimately, the goal of these advancements is to achieve fully personalised medicine, where treatment is tailored not only to the disease but also to the individual patient’s biological and clinical profile. As these technologies continue to evolve, interventional radiology is set to become an even more central component of comprehensive cancer care. 14,15