Liver transplantation for hepatocellular carcinoma: Management after the transplant

Abstract

Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post‐LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post‐LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.

Risk factors for hepatocellular carcinoma recurrence after liver transplantation

“…A critical point that can be applied to the majority of models that aim to predict HCC recurrence is that the time of recurrence after transplant is rarely mentioned. Although this time is variable, several studies have identified a peak of HCC recurrence within 2-3 years after transplant while after 5 years, recurrence is very infrequent [117] . Since HCC recurrence after LT impacts negatively on overall survival, the time to recurrence represents an important prognostic factor.…”

“…Since HCC recurrence after LT impacts negatively on overall survival, the time to recurrence represents an important prognostic factor. Early (within 12 months after LT) HCC recurrence is associated with a more severe prognosis [117] . The reasons why it occurs may be related to the presence of non-detected extra-hepatic HCC metastases at the time of transplant, or as a consequence of circulating neoplastic clones of HCC able to engraft and growing in the transplanted liver or in other organs.…”

“…These data strongly suggest maintaining a very stringent surveillance of the recurrence of HCC in the first 3 years after LT, prolonging up to the fifth year, since very late recurrence of the tumor is also associated, if promptly discovered and treated, with a better prognosis [10] . Regarding the best way to perform surveillance, in the absence of specific evidence-based risk stratification criteria, the majority of LT centers suggest to perform a total body contrast CT or MRI scan every 6 months for at least 3 years, that can then be extended to 5 years after LT, in addition to AFP serum measurements [117] .…”

Is post‐transplant chemotherapy feasible in liver transplantation for colorectal cancer liver metastases?

“…Similarly, in HCC, post‐operative systemic treatment post‐LT lacks robust evidence [9]. In 2015, a meta‐analysis by Lin et al evaluated the role of adjuvant chemotherapy post‐LT in HCC patients, demonstrating a benefit in terms of overall survival [Hazard Ratio (HR): 0.34; 95% Confidence Intervals (CI): 0.22‐0.52; P < 0.001] and disease‐free survival (HR: 0.87; 95% CI: 0.78‐0.95; P = 0.004); unfortunately, the quantitative analysis of adverse events was not possible because of the anecdotal nature of the data collected, but the incidence of severe adverse events seemed to be low and included myelosuppression, neurotoxicity, and infection [10].…”

AFP ratio predicts HCC recurrence after liver transplantation

“…Currently, there is no clear guideline for follow-up and surveillance of patients after LT for HCC [12]. It would be desirable to predict the individual risk for HCC recurrence more accurately, thereby reducing the need for repeated radiation exposure and the use of contrast agents.…”