# Non-Transplantable Recurrence After Initial Liver Resection of Hepatocellular Carcinoma: A Narrative Review

## TL;DR

This paper reviews factors that increase the risk of aggressive liver cancer recurrence after surgery, which can prevent liver transplants and worsen outcomes.

## Contribution

The paper identifies clinical and histopathologic risk factors for non-transplantable recurrence after liver resection for hepatocellular carcinoma.

## Key findings

- Larger tumor size, multiple tumors, and elevated alpha-fetoprotein levels are linked to non-transplantable recurrence.
- Microvascular invasion and satellite nodules are associated with aggressive tumor biology and poor transplant eligibility.
- Improved preoperative risk stratification can guide better treatment decisions for liver cancer patients.

## Abstract

Hepatocellular carcinoma is a form of liver cancer that is associated with high rates of mortality worldwide. The main treatment options for patients with hepatocellular carcinoma include surgical removal of the tumor or undergoing a liver transplant. Although removing the tumor is less invasive than a liver transplant, the cancer frequently recurs. In certain circumstances, the recurrence can be aggressive and not amenable to curative treatments such as liver transplant. Therefore, we aimed to determine what factors put patients at higher risk for this kind of aggressive recurrence to help identify which patients would benefit most from early transplant versus tumor removal alone. A clearer understanding of these risk factors can improve decision-making, reduce the chance of losing the opportunity for a transplant, and guide more personalized care. The findings may also help researchers design better prediction tools and future studies to improve outcomes for people with liver cancer.

Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying liver disease, yet its application is limited by organ scarcity, waitlist dropout, and eligibility criteria. Hence, LR remains widely used due to greater accessibility but is associated with high recurrence rates. Salvage LT is a treatment option for patients with HCC recurrence post-LR, but up to 40% of patients develop non-transplantable recurrence (NTR), defined as recurrence beyond transplant criteria, which precludes LT and is associated in poor outcomes. Methods: The present review aims to summarize the current state of evidence on the comparison of LT and LR, the management of recurrent HCC, and the risk factors associated with NTR. Results: Clinical and histopathologic factors consistently associated with NTR across studies include larger tumor size, multiple tumors, elevated alpha-fetoprotein levels, underlying liver fibrosis or cirrhosis, microvascular invasion, and satellite nodules—features that reflect aggressive tumor biology and impaired hepatic reserve. Conclusions: Improved preoperative risk stratification and identification of patients at high risk for NTR is essential to inform optimal treatment selection.