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Zhang et al. Late recurrence of hepatocellular carcinoma

Unfortunately there is little evidence of the survival as greater than 2 alcoholic beverages daily for at
benefits following treatment for recurrent HCC least 10 years), and other chronic liver diseases.
following transplant. In addition, few studies have Information was based on available medical records
examined risk factors in recurrent HCC after transplant and interviews by a single physician.
or prognostic factors for survival after recurrence.
Moreover, while tumor recurrence tends to happen Laboratory data collected included serum bilirubin,
within the first two years following transplantation, late albumin, prothrombin time, creatinine, alanine
recurrence can occur and the pathobiology underlying aminotransferase, aspartate aminotransferase,
these cases is not well understood. This study aims platelet count and alpha-fetoprotein (AFP). Laboratory
to identify and characterize cases of late recurrent data that was used for the study had been obtained
HCC after transplantation in Hawaii, a state with a within 2 weeks of initial visit or drawn at the time
high burden of liver disease and cancer due to a large of the visit. Serum bilirubin, prothrombin time with
population of Asians and Pacific Islanders with viral international normalized ratio (INR) and creatinine
hepatitis. [5-7] were used to calculate the Model for End-stage Liver
Disease (MELD) score. Dynamic imaging with CT or
METHODS MRI was performed to determine if Milan criteria were
met (single tumor ≤ 5 cm or up to 3 tumors ≤ 3 cm
This is a retrospective analysis of 88 patients who each, no vascular invasion, no extrahepatic spread).
underwent LT for HCC from 1993 to 2015. All patients Patients who met Milan criteria initially or who could
were referred to a group of physicians associated with be downstaged with locoregional therapy to meet
the medical center with the only LT program in the Milan criteria were considered for liver transplantation.
state of Hawaii. It is also the primary referral center
for hepatobiliary surgery for American Samoa, Guam, We also noted the type of locoregional therapy that
Saipan, and the Marshall Islands. This clinic and the was performed before LT including RFA and TACE.
transplant center were initially affiliated with Hawaii Pathology reports were also examined to determine
Medical Center-East (formerly St. Francis Medical the size and number of HCC lesions present, the
Center) and after 2012, the Queens Medical Center. amount of tumor necrosis, the location of tumors, and
This center sees about 60-70% of the HCC cases in presence of vascular invasion.
Hawaii. This study was approved by the University of
Hawaii Institutional Review Board. Data analysis was performed using Microsoft Excel
and Statistical Package for the Social Sciences
HCC was diagnosed histologically by percutaneous software to identify potential predictors for recurrent
biopsy or at surgery. The diagnosis of HCC was HCC. Fisher’s and chi-square analysis was performed
made with only imaging if a contrast-enhanced study and P values < 0.05 were considered significant.
[dynamic computed tomography (CT) or magnetic
resonance imaging (MRI)] showed typical arterial Five patients were identified as having a “late”
enhancement with “washout” in the venous phase recurrence, defined as the diagnosis of HCC occuring
as described by the American Association for the more than 5 years after the date of LT. Late recurrence
Study of Liver Disease guidelines. All patients cases were examined in detail for post-LT course, use
[8]
received transplant livers from deceased donors. For of immunosuppression, site of recurrence, treatment
immunosuppression after LT, patients all received for recurrence, and response to treatment.
basiliximab for induction, steroids, tacrolimus, and
mycophenolate mofetil. All patients were weaned RESULTS
off of steroids after 6 months and maintenance
immunosuppression was continued with tacrolimus or Of 1,200 patients in our database of patients treated
tacrolimus/mycophenolate. for HCC, 88 underwent LT for HCC and had the
following characteristics were shown in Table 1: mean
Information on demographics, medical history, age 56.6 years, 83% male, 54.5% Asian, 10.2%
laboratory results, tumor characteristics, treatment, Pacific Islanders, 58% hepatitis B positive, 61.4%
and survival was collected via clinical interviews. hepatitis C positive, 30.7% with diabetes, and 46.6%
Demographic data included age, gender, birthplace, with normal AFP (< 20). Locoregional therapy was
and the patient’s self-reported ethnicity. Data collected performed in 67 patients (76.1%) with 26 receiving
on medical history included diabetes mellitus, only RFA and 17 received only TACE. Cases with
hyperlipidemia, smoking, and risk factors for HCC single tumors less than 2.5 cm in easily accessible
including viral hepatitis, alcohol abuse (defined locations were chosen for RFA. Cases with larger

Hepatoma Research ¦ Volume 3 ¦ April 10, 2017 59