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Page 2 of 10 Simsek et al. Hepatoma Res 2020;6:11 I http://dx.doi.org/10.20517/2394-5079.2019.51

INTRODUCTION
Liver transplant (LT) has become the treatment of choice in patients with hepatocellular carcinoma (HCC)
[1]
and cirrhosis who meet the Milan criteria (MC) . Although additional extended criteria models have been
[2,3]
proposed, HCC recurrence following LT remains an unfortunate incident associated with poor survival .
Tumor biology and alpha fetoprotein (AFP), as well as tumor size and number, have been proposed by
[4-6]
various groups as other potentially relevant factors of tumor recurrence .

Overall, two thirds (2/3) of patients, who develop recurrent HCC post-LT, present with extrahepatic
[7,8]
recurrence . The treatment of choice in post LT HCC recurrence is determined based on the site and the
[8]
extent of the recurrence . However, treatments are not standardized and mostly based on expert opinion
and retrospective studies . Surgical treatment options have been proposed with promising outcomes in
[9]
selected patients [10,11] . Locoregional therapy options, transarterial chemoembolization, radiofrequency
[9]
ablation, and stereotactic radiation are considered in selected cases .

In a recent report, we published our experience in LT recipients with HCC at the Johns Hopkins University
[12]
Comprehensive Liver Transplant Center . As a follow-up study, we aimed to study the clinicopathological
features and outcomes of 26 cases with HCC recurrence following LT. In addition, we evaluated the details
on the outcomes and the application of different treatment modalities in this group.

METHODS
The study was approved by the institutional review board at the Johns Hopkins Hospital. HCC-related
deceased donor LT recipients between January 2005 and December 2015 were evaluated. In total, 26
patients with post-LT HCC recurrence were identified among 165 recipients who were included in the
study. All recipients were listed following a standard work up and discussion at the weekly selection
meeting. They were within Milan criteria or downstaged into Milan criteria. The transplant was performed
by piggyback technique. Postoperative HCC surveillance consisted of contrasted cross-sectional imaging
with computerized tomography or magnetic resonance imaging with AFP every three months for the
first year and every six months for the second and third years. There was no set therapeutic protocol for
recurrence; treatment options were discussed in a multidisciplinary fashion. The Pre-LT AFP was obtained
within the past three months prior to deceased donor liver transplantation (DDLT) and immediate post-LT
AFP was obtained within three months post DDLT.

Data on clinical, radiologic, pathology, HCC recurrence, and survival were collected from the records,
reviewed, and analyzed. Explant pathologies were reviewed retrospectively, and the following tumor
parameters were collected: size, number of lesions, microvascular invasion status, and differentiation. It was
determined whether patients met the Milan or University of California San Francisco (UCSF) criteria based
on the number and size of HCC lesions on explant pathology. The data collected for categorical variables
were reported as percentages. Data for continuous variables were reported by the mean and standard
deviation. Patient survivals were analyzed using Kaplan-Meier statistics. STATA V.13 (StataCorp college
station, TX) was used to perform the statistical analyses.

RESULTS
Patient characteristics
Among the deceased donor LT recipients, HCC was the primary indication for transplantation varying
from 21% to 53% of patients [Figure 1] according to the year. Clinical information on the 26 LT recipients
with recurrent HCC is summarized in Table 1. Patients were predominantly male (88.5%) with a mean age
of 59 years (range 47-72 years). The majority of recipients were white (n = 17, 65.4%), followed by African
American (n = 7, 27.0%) and Asian (n = 2, 7.6%) ethnicities. Primary etiology of liver disease was chronic