Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

Abstract

The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival. Patients and Methods: Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence. Cox's regression analysis was conducted revealing risk factors for HCC recurrence. Results: HCC recurred in 47 of 252 analyzed patients with a median time to recurrence of 20 months. Patients with AR (28.6%) had a significantly higher frequency of recurrence compared to patients without AR (13.0%, p=0.002). Multiple Cox regression analyses identified AR within 20 months to be an independent risk factor for HCC recurrence both as dichotomized (HR=2.91, 95%CI: 1.30-6.53; p=0.009) and as a continuous variable (HR=1.81, 95%CI: 1.28-2.54; p=0.001). HCC recurrence and AR were associated with higher grades of liver fibrosis one year after LT, when compared to patients without AR (p=0.019). Conclusion: Our results demonstrate an association of AR with HCC recurrence after LT with implications for intervals of monitoring in tumor surveillance. Graft fibrosis and immune mechanisms are potentially related and causal interactions are worth further investigation.

The Role of Immunosuppression for Recurrent Cholangiocellular Carcinoma after Liver Transplantation

“…Unlike in HCC, the importance of acute cellular rejection seems to be rather secondary in the CCA context, although a definite statement is not possible due to the rarity of the diagnosis in the present setting [ 33 , 34 ]. In addition, we were able to demonstrate a significantly better survival, even after a recurrence, if no lymph node metastases existed.…”

The RETREAT score provides valid predictions regarding hepatocellular carcinoma recurrence after liver transplantation

“…In addition, some data suggest that early posttransplant calcineurin inhibitor (CNI) reduction is associated with a reduced rate of tumor recurrence [14]. In addition, a possible association between posttransplant HCC recurrences and acute rejection was recently published [15], which suggests that simply reducing the load of immunosuppression might not be the solution. Even though more research is needed to clarify whether patients with high or intermediate RETREAT scores benefit from adjuvant therapies or specific immunosuppression protocols, such as early CNI minimization or an early switch to everolimus/sirolimus-based regimens, a posttransplant prognostic score could help stratify patients with more accuracy in future studies in this field, which could lead to the identification of improved and individualized immunosuppression strategies, taking into account the tumor recurrence risk.…”

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

“…Gul-Klein et al found that recurrence was over twice as frequent in patients with a history of acute rejection incidents in comparison to patients without such incidents. Lai et al reported that the recurrence risk is 18 times higher in patients treated with steroid bolus in comparison to patients without rejection or without clinical manifestation of rejection who were not treated with steroids [ 112 , 113 ].…”