Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma

Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2-3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1-2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.

Automated summary

Despite strict selection criteria, up to 20% of patients experience hepatocellular carcinoma recurrence after liver transplantation. There are no established adjuvant treatments to prevent recurrence, however, a balanced use of immunosuppression is advised. Pre- and post-transplant predictors of recurrence can help determine the frequency and duration of follow-up. Survival after recurrence is poor, with timing being a key factor. Treatment options depend on the timing and presentation of the disease. Surgical treatment provides a survival benefit, especially in late recurrence, while the effectiveness of locoregional treatments is still uncertain. Sorafenib is proven to be safe and effective, while data for other drugs are limited.