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Zhang et al. Late recurrence of hepatocellular carcinoma

Table 1: Baseline characteristics of patients in study (n = 88) did not predict recurrence [Table 2].
Characteristics Data, n (%)
Age, years, mean ± SD (range) 56.6 ± 6.1 (41-72) Recurrent HCC occurred in 15 cases (17.0%) with
Males 73 (83.0) mean time to recurrence of 3.96 ± 3.99 years. Seven
Ethnicity patients recurred within 2 years and 5 recurred > 5
Asian 48 (54.5) years post-LT. All late recurrences involved males in
Pacific Islanders 9 (10.2) their 50s, recurring at a mean 8.5 years (range 5.2-
Black 1 (1.1) 13.4 years). Explanted livers showed 1 with vascular
Hispanic 2 (2.3) invasion, 2 with > 4 tumors and 2 with single tumors.
White 26 (29.5)
Mixed 2 (2.3) Recurrences occurred in chest wall (2), liver (2), lung
Hepatitis B 51 (58.0) (2), bone (1) and pelvis (1), with 2 patients having
Hepatitis C 54 (61.4) recurrent tumors in multiple sites. Four patients died
Diabetes 27 (30.7) within 18 months of late recurrence. The fifth patient is
AFP, mean ± SD 669.7 ± 3,739.6 alive for 3 years after ablation of liver recurrence and
Patients receiving locoregional therapy 67 (76.1) treatment with sorafenib and everolimus. Table 3 lists
RFA only 26 (29.5) details of the late recurrence cases and Table 4 shows
TACE only 17 (19.3) a comparison of early and late recurrence cases.
AFP: alpha-fetoprotein; RFA: radiofrequency ablation; TACE:
transarterial chemoembolization Clinical summaries of the 5 cases of late recurrence
are reported below.
tumors and multiple tumors were treated with TACE.
Median duration of follow-up was 6.4 years (mean 6.8 Case 1
years, range 8 days-17.2 years). The first case is a 53-year-old Chinese male with
hepatitis B cirrhosis and 2 liver masses (3.4 and 2.1 cm).
Univariate analysis suggested the presence of AFP was 2,397 ng/mL and liver biopsy showed a
microvascular invasion as seen on pathology and size well-differentiated HCC. He underwent RFA followed
of the largest tumor in the explant to be predictors by TACE and LT 1 month later. The explanted liver
of recurrence of HCC after transplant. Other factors showed multifocal HCC without microvascular
including age, gender, race, presence of hepatitis B invasion including 4.5 cm, 3.0 cm and 1.8 cm masses
or C, diabetes, AFP level, locoregional treatment, and with 95-100% necrosis, and a 1.8 cm caudate lobe
presence of 4 or more tumors in the explanted liver mass with 10% necrosis.

Table 2: Characteristics of patients with recurrence vs. without recurrence, n (%)
Characteristics Recurrence (n = 15) No recurrence (n = 73) P value
Age, years, mean ± SD 58.1 ± 3.1 56.3 ± 6.5 0.30
Males 11 (73.3) 62 (85.0) 0.28
Asians 10 (66.7) 38 (52.1) 0.40
Hepatitis B 8 (53.3) 21 (28.8) 0.08
Hepatitis C 7 (46.7) 47 (64.4) 0.25
Diabetes 6 (40.0) 21 (28.8) 0.54
Imaging: largest tumor size, cm, mean ± SD 3.1 ± 1.2 2.9 ± 1.3 0.60
Explant: largest tumor size, cm, mean ± SD 3.9 ± 2.0 2.4 ± 1.2 0.001
Explant: largest tumor > 3 cm 6/11* (54.5) 19/66* (28.8) 0.16
Imaging: no. of tumors, mean ± SD 1.2 ± 0.6 1.3 ± 0.6 0.60
Explant: no. of tumors, mean ± SD 3.1 ± 3.6 2.0 ± 1.9 0.13
Explant: > 4 tumors 5/13* (38.5) 10/67* (15.0) 0.06
Well differentiated tumor 2/13* (15.4) 15/58* (25.9) 0.72
Met milan criteria 13 (86.7) 57/72* (79.2) 0.73
AFP at diagnosis, ng/mL, mean ± SD 829.9 ± 2,401.1 637.7 ± 3,966.1 0.86
AFP > 500 ng/mL 2/14 7/70 0.64
AFP > 1,000 ng/mL 2/14 5/70 0.33
Lab MELD score, mean ± SD 11 ± 3.9 12 ± 3.8 0.74
Received locoregional therapy 12 (80.0) 55 (75.3) 1.00
Waiting time (from diagnosis to LT), days, mean ± SD 193.4 ± 163.9 315.8 ± 367.3 0.21
Explanted liver met Milan criteria 7/13* (53.8) 47/67* (70.1) 0.33
Explanted liver with microvascular invasion 5/13* (38.5) 1/59* (1.7) 0.001
*Data not available for all patients. No. of cases for which data was available is indicated. AFP: alpha-fetoprotein; MELD: Model for End-
stage Liver Disease; LT: liver transplantation
60 Hepatoma Research ¦ Volume 3 ¦ April 10, 2017