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Page 8 of 12 Fung et al. Hepatoma Res 2018;4:62 I http://dx.doi.org/10.20517/2394-5079.2018.92

A

B

Figure 3. A and B: Immunohistochemical study for HBsAg showing positive cytoplasmic staining in metastatic tumour cells in lungs

A total of 16 patients lost HBsAg after transplantation, with subsequent re-appearance of HBsAg and
recurrence of HCC. There was a significant correlation between the time of tumour recurrence and the time
of HBsAg re-appearance (r = 0.551, P = 0.027), as shown in Figure 2B. There was no significant difference
in the median time of recurrence of HCC vs. reappearance of HBsAg after LT (21 months vs. 18 months
respectively, P = 0.809). Of these 16 patients, 2 had recurrence limited to the liver, and the remaining 14
patients had extra-hepatic metastatic lesions to the lungs, bones, lymph nodes, and adrenal glands. Histology
from the site of recurrence was available for 12 of 16 patients, with specimens from 2 patients staining
positive for HBsAg (both from metastatic lung tissues) [Figure 3]. One had recurrence at 9 months after
transplantation, with HBsAg re-appearance at 10 months. The other patient had recurrence at 7 months,
with HBsAg re-appearance at 14 months.

Quantitative HBsAg levels with HCC recurrence
There was a significant higher median level of hs-HBsAg at the time of transplant for those with early HCC
recurrence compared to those without (72.85 vs. 69.70 IU/mL respectively, P = 0.018). After transplant, the
median hs-HBsAg levels at month 1, 3, 6, and 12 was 0.0008 (range, 0-50.6855), 0 (range, 0-1.0827), 0 (range,
0-0.1642), and 0 (range, 0-0.1310) IU/mL respectively. Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients
with levels ≥ 0.0005 IU/mL was associated with a significantly higher rate of early HCC recurrence compared
to those with lower levels at 3 months post transplant (28.6% vs. 3.0% respectively at 3 years post transplant,
P = 0.006) [Figure 4A], and at 6 months post transplant (26.9% vs. 2.9% respectively, P = 0.006) [Figure 4B].
In contrast, using the conventional qualitative HBsAg assay, there was no significant difference in HCC
recurrence observed between positive and negative HBsAg status at 3 and 6 months post transplant (P = 0.845
and P = 0.449, respectively). No significant difference in early HCC recurrence rate was observed at 1 month
post transplant using this cut-off (P = 0.162) [Figure 4C].

DISCUSSION
In CHB patients who achieve HBsAg seroclearance by conventional assays, a substantial proportion of