Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, accounting for the majority of primary liver cancer cases.

It is the fourth leading cause of cancer-related deaths worldwide.

Although liver transplantation (LT) is the most definitive treatment for HCC in certain patients, the decision to proceed with LT depends on several factors, including tumour characteristics and the availability of donor organs.

This review updates the current understanding of HCC, the various criteria for liver transplantation, and the advancements in bridging and downstaging therapies.

Epidemiology

The risk factors for developing HCC are primarily related to underlying liver diseases, including cirrhosis and chronic infections with hepatitis B and C viruses.

In recent years, there has been an increase in HCC cases related to alcohol-related liver disease and metabolic-associated steatohepatitis (MASH/MASLD), with the latter expected to contribute to a significant rise in cases globally.

The incidence of HCC is higher in men and varies by geographical region, with the highest rates observed in East Asia.

Surveillance and Early Detection

HCC is often asymptomatic in its early stages, which leads to a poor prognosis when diagnosed at advanced stages.

Therefore, screening for high-risk individuals, such as those with cirrhosis, is crucial.

The use of ultrasound, along with alpha-fetoprotein (AFP) testing, is common for surveillance.

However, these methods have limitations in terms of sensitivity and specificity, especially in obese patients.

More advanced imaging techniques like MRI and CT scans are utilised for further evaluation when suspicion arises.

Staging and Treatment Criteria

The Barcelona Clinic Liver Cancer (BCLC) staging system remains the most widely used for HCC, incorporating tumour size, liver function, and performance status.

For liver transplant eligibility, the Milan Criteria are commonly applied, though other extended criteria have been proposed to allow for the inclusion of patients with more advanced tumours.

Additionally, patients with HCC may be prioritised for LT using the Model for End-Stage Liver Disease (MELD) score, with a MELD exception for those with HCC.

Bridging and Downstaging Therapies

For patients awaiting LT, bridging therapies, including locoregional treatments like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), are commonly used to prevent tumour progression.

Downstaging strategies, such as TACE and systemic therapies, aim to reduce tumour burden and make patients eligible for LT.

These treatments have shown promising results in improving survival outcomes post-transplant.

Liver Transplantation for HCC

Liver transplantation offers a curative treatment for HCC, as it eliminates both the tumour and the cirrhotic liver.

However, the limited availability of donor organs and strict eligibility criteria make LT not universally applicable.

Over time, the criteria for LT have expanded to include patients with larger or more numerous tumours, provided other factors such as tumour differentiation and AFP levels are favourable.

While survival rates post-LT for HCC patients are high, the risk of recurrence remains a significant challenge.

Systemic Therapies and Post-Transplant Monitoring

Advances in systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have provided additional treatment options for patients with advanced HCC.

These therapies are increasingly used in bridging and downstaging strategies.

Post-transplant surveillance for HCC recurrence typically involves imaging and monitoring of AFP levels.

While the prognosis for recurrent HCC is generally poor, aggressive treatment options, including surgery and systemic therapies, have shown potential in improving patient outcomes.

Conclusion

Liver transplantation remains a cornerstone in the treatment of HCC for appropriately selected patients.

However, due to limited organ availability and strict eligibility criteria, it is essential to continue exploring alternative treatment options, including bridging and downstaging therapies.

The role of systemic therapies in the management of HCC is expanding, and future research will likely focus on refining selection criteria, improving early detection methods, and enhancing post-transplant care to reduce recurrence rates and improve long-term outcomes for patients with HCC.

The study was recently published in the Journal of Clinical and Translational Hepatology.

Source: Xia & He Publishing Inc.