Early Versus Late Hepatocellular Carcinoma Recurrence After Transplantation: Predictive Factors, Patterns, and Long-term Outcome

Abstract

Background. Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short- and medium-term outcomes after LT. Methods. A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed. Results. Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5- and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence. Conclusions. Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-term survival.

Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice

“…In fact, while recurrence following transplantation for HCC has been reported to be as low as 10-14%, recurrence after liver resection for early-stage HCC can be as high as 50-70%. [2][3][4][5][6] Liver transplantation is not, however, available to many patients due to limited services at certain medical centers, poor access to liver donors, and prolonged wait times. 19,20 In fact, a subset of patients with early-stage HCC and underlying chronic liver disease who are on the waiting list are at risk of tumor progression and drop out from the list.…”

“…Liver transplantation may be the preferred treatment option over resection as tumor recurrence is lower (10-14%) given that both the cirrhotic liver and HCC are removed. [2][3][4] However, the shortage of donor organs limits the wide applicability of liver transplantation. In turn, surgical resection is often utilized, as the availability of donor organs is not a concern.…”

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study

“…Based on the patterns of recurrence as reported by previous studies, HCC recurrence occurring within two years after curative treatment such as RFA or surgery is categorized early recurrence (ER) while recurrence after two years is termed as late recurrence (LR) (17)(18)(19). ER has been shown to most likely originate from micro-metastases of the initial tumor (19,20).…”

High trough levels of everolimus combined to sorafenib improve patients survival after hepatocellular carcinoma recurrence in liver transplant recipients

“…HCC recurrence is one of the critical complications after LT, because of its poor prognosis. The MST after HCC recurrence was previously reported as less than 1year [12, 31]. In this study, with long‐term follow‐up (median 55.2 months {95%CI: 49.2–62.4} months), the 5‐ and 10‐year patient survival were respectively 72.4% and 52.4%.…”