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Sempokuya et al. Hepatoma Res 2019;5:38 I http://dx.doi.org/10.20517/2394-5079.2019.013 Page 3 of 10

Data collected
We obtained demographic (age, sex and ethnicity), anthropometric information [height, weight and body
mass index (BMI)], comorbidities, etiology of HCC, tumor size/characteristics, laboratory values, staging,
therapeutic modalities, recurrence and survival information. Ethnicity was categorized as “Caucasian”,
“Asian”, “Pacific Islanders”, and “Others”. Comorbidity data collected include diabetes mellitus, smoking
status, hyperlipidemia, and hypertension.

Significant alcohol use was defined as at least 2 alcoholic beverages daily for 10 years. Positive smoking
history included both past and present use of cigarettes. Laboratory values include creatinine, alanine
aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, prothrombin time with
international normalized ratio, platelet, neutrophil, lymphocytes, hepatitis B virus (HBV) and hepatitis
C virus (HCV) serologies and pre-treatment alpha feto protein (AFP). We defined normal AFP as less than
[16]
20 ng/dL. Based on these values, we calculated model for End-Stage Liver Disease (MELD) score ,
[17]
fibrosis-4 (FIB-4) index for liver fibrosis , AST/platelet ratio index (APRI) and neutrophil-lymphocyte
ratio (NLR). The American Joint Committee on Cancer (AJCC) staging system was incorporated with
tumor size, number, and location of tumor. Tumor size was categorized by the largest diameter by ≥ 5 cm
or < 5 cm. Status on underlying cirrhosis, rupture at presentation, and macrovascular invasion on imaging
was also noted. Cirrhosis was determined with imaging when tissue was not available. Therapeutic
modalities included liver transplantation, hepatic resection and locoregional therapies (radiofrequency
ablation (RFA), cryosurgery, transarterial chemoembolization (TACE), percutaneous ethanol injection
and yttrium90 transarterial radioembolization). Liver resection was performed on patients with Childs-
Turcotte-Pugh (CTP) A and early B with CTP of 7 without ascites or encephalopathy. Patients who received
[18]
liver transplantations had unresectable tumor who met Milan criteria or prior liver resection with
recurrence of HCC which met Milan criteria. Single tumors size less than 6.5 cm that were down staged to
meet Milan criteria was also evaluated for liver transplantation since 2007.

Statistical analysis
Statistical analysis was conducted using statistical package for social services (SPSS) (version 23.0. IBM
Corp., Armonk, NY, USA), R version 3.4.1 (The R foundation for Statistical Computing, Vienna, Austria)
as well as EZR version 1.36 (Division of Hematology, Saitama Medical Center, Jichi Medical University,
[19]
Japan ). Primary objective of this study is to elucidate the factors associated with 10-year survival.
Secondary objective of this study is to elucidate management strategies for HCC recurrence that allows
for long term survival. Comparison of binary variables were accomplished by chi-square test. Continuous
variables were analyzed by T test to obtain mean, standard deviation (SD) and standard error of mean
(SE). Likelihood ratio was calculated for binary variables. Nominal regression was used to create a
regression model. Variables included in this model as followings: age was categorized as a binary variable
with < 65-year-old and ≥ 65-year-old. Demographic data, etiology of HCC, BMI, comorbidity, AFP as binary
variable (normal vs abnormal), tumor size as a binary variable, Milan criteria, rupture status, and therapeutic
modalities. Multivariable regression model was also created to analyze these variables with P < 0.1 on
univariate analysis. We also conducted differences between 10-year survivors and non-survivors on time
to recurrence for transplant and hepatic resection. Kolmogorov-Smirnov test was used to test for normal
distribution. Mann-Whitney U test was used to compare time to recurrence and recurrence free survival
between 10-year survivors and non-survivors. P < 0.05 is considered as statistically significant.

RESULTS
Baseline characteristics
This study included 234 patients: 70 patients who survived 10 years after the diagnosis of HCC and 164
patients in the entire cohort who either had liver resection or transplant and died before 10 years. Baseline