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Authors Zhang Y, Huang J, Chen J, Yang K, Chen J, Xu L, Zhou Z, Chen M
Received 16 December 2017
Accepted for publication 29 January 2018
Published 27 March 2018 Volume 2018:10 Pages 599—611
DOI https://doi.org/10.2147/CMAR.S160047
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Professor Kenan Onel
Background: Although hepatitis B virus (HBV) is still one of the most common
etiological factors for hepatocellular carcinoma (HCC), the association between
the HBV mutations and the clinical characteristics and prognosis of HBV-related
HCC patients (HBV-HCC) after surgical resection remains largely unknown.
Materials and
methods: A cohort of 131 consecutive patients
who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV
genotype and 14 genomic mutations, which have been reported to relate to HCC in
liver samples, were sequenced. The associations between the genomic mutations
and clinical characteristics and outcomes were analyzed.
Results: Both A1762T/G1764A mutation and Pre S deletion related to worse overall
survival (OS, p =0.040 and p <0.001, respectively) and
disease-free survival (DFS, p =0.040 and p <0.001, respectively), G1899A
mutation related to worse OS (p =0.030),
A1762T/G1764A mutation correlated with tumor size (r =0.204, p =0.019), G1899A mutation
correlated with vascular invasion (r =0.332, p <0.001), and Pre S deletion
correlated with alpha-fetoprotein (AFP; r =0.254, p =0.003) positively. Multivariate
analysis with Cox proportional hazards model revealed that both A1762T/G1764A
mutation and Pre S deletion were independent prognostic factors for OS (hazard
ratio [HR]=3.701, 95% CI=1.390–9.855, p =0.009, and
HR=4.816, 95% CI=2.311–10.032, p <0.001,
respectively) and DFS (HR=3.245, 95% CI=1.400–7.521, p =0.006, and HR=2.437, 95%
CI=1.311–4.530, p <0.001,
respectively), and patients with dual mutations were found to have the worst OS
and DFS (p <0.001 and p <0.001, respectively).
Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have
early recurrence (p =0.042 and p =0.019, respectively).
Conclusion: HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were
associated with worse prognoses and early recurrence for HBV-HCC patients after
surgery.
Keywords: hepatitis B virus, mutation, hepatocellular carcinoma, prognosis