Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

Abstract

Background/AimsThe most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.MethodsNinety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).ResultsThe 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05).ConclusionsInduction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.

Prognostic Impact of Intraoperative Blood Loss in Liver Transplant Patients with Advanced Hepatocellular Carcinoma Blood Loss and HCC Recurrence

“…In addition, IOBL was shown to provide immunosuppressive effects by reducing natural killer cell activities and T-helper 1 lymphokines (37). In combination with post-transplant immunosuppressive therapy, this might result in a state of 'overimmunosuppression', which is known to promote tumor outgrowth (38). Furthermore, tissue ischemia itself was demonstrated to up-regulate pro-inflammatory and pro-angiogenic factors (hypoxia-inducible factor 1α, vascular endothelial growth factor), adhesion molecules (E-selectin, tumor-necrosis factor α), chemokines (interferon-γ-induced protein 10) and matrix metalloproteinases (MMP, MMP-10) (18)(19)(20)(39)(40)(41)(42).…”

Review on immunosuppression in liver transplantation

“…Use of muromonab (although not available anymore) and ATG has been shown to be associated with increased risk of HCC recurrence [103] . Also, Basiliximab has been shown to have a negative impact on tumor recurrence when used as an induction therapy in HCC patients receiving LT [104] . MMF possesses anti-proliferative properties but has not been documented to play a role in prevention of HCC recurrence [64,102] .…”

Glutamate Dehydrogenase and Alkaline Phosphatase as Very Early Predictors of Hepatocellular Carcinoma Recurrence after Liver Transplantation

“…The immunosuppressive regimen selected has also been found to influence HCC recurrence: calcineurin inhibitors (CNIs) and steroids have been shown to increase the risk of recurrence, whereas mammalian target of rapamycin (mTor) inhibitors seem to have the potential to reduce the risk of recurrence [8,9]. Which immunosuppressive regimen can decrease tumor recurrence is still a matter of debate.…”