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 tumor 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 utilized 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 tumor 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 tumors. Additionally, patients with HCC may be prioritized 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 tumor progression. Downstaging strategies, such as TACE and systemic therapies, aim to reduce tumor 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 tumor 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 tumors, provided other factors such as tumor differentiation and AFP levels are favorable. 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.
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The study was recently published in the Journal of Clinical and Translational Hepatology .
The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study's novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.
