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Tong et al. Hepatoma Res 2019;5:36 I http://dx.doi.org/10.20517/2394-5079.2019.005 Page 9 of 13

Figure 2. Recurrence-free survival of 164 patients with hepatocellular carcinoma

In the report herein, we first attempted to determine factors associated with tumor growth rate in patients
with HBV- and HCV-related HCC. By regression tree analysis of 19 variables, AFP levels < or > 16.7 ng/mL
best discriminated between slow and fast growing tumors respectively [Figure 1]. In a previous report, the
initial AFP levels did not correlate with tumor growth rate but, in those patients with repeated AFP values
which showed an exponential increase in AFP, the AFP doubling time was closely related to the tumor
[6]
doubling time . Other studies comparing AFP values > 100 ng/mL, > 200 ng/mL, and > 400 ng/mL showed
that each of the AFP levels correlated with faster tumor doubling times [10,11,20] . These findings indicate that
elevated AFP levels are significant indicators of tumor doubling time.

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In patients with AFP ≥ 16.7 ng/mL, the next best discriminator was platelet counts < or > 140,000 mm .
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Within the platelet count ≥ 140,000 mm node, the mean platelet count was 201,345 mm (median
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192,000 mm ). There were only two patients with thrombocytosis (385,000 mm and 420,000 mm ). In
previous reports, thrombocytosis was noted in 2.70% to 8.20% of HCC patients and was associated with
overproduction of thrombopoietin by liver cancer cells [21,22] . In these studies, thrombocytosis was associated
with larger tumor volumes and higher levels of serum AFP in Asian HCC patients, and with larger tumor
sizes, younger patients, and less cirrhosis in European HCC patients. One possible explanation for large
tumor sizes in patients with higher platelet counts or in cirrhotic patients with “higher than expected” platelet
counts is that platelets are a source of a number of HCC growth stimulants including vascular endothelial
[22]
growth factor, platelet-derived growth factor, serotonin, and fibroblast growth factor . In the study herein,
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patients with platelet counts ≥ 140,000 mm had a faster mean TGR compared to those with platelet counts <
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140,000 mm (39.4% per month vs. 21.0% per month, respectively).
There have been few reports on the relationship between serum albumin levels and tumor doubling time. In
earlier studies, Child-Pugh scores did not influence tumor doubling times [6,20] . A recent study showed that
Korean HCC patients with tumor doubling times < 2 months had significantly lower mean albumin levels
[23]
than those with tumor doubling times > 2 months (3.20 g/dL vs. 3.50 g/dL, P = 0.003) . In our report, the
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TGR of patients in the platelet count < 140,000 mm node were further discriminated into fast and slow TGR
by albumin levels < or > than 3.55 g/dL (31.4% per month vs. 9.15% per month). This finding suggests that
cirrhosis patients with poor liver synthetic function have less ability to confine the growth of HCC.