Liver disease

Hepatitis

Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels

M-F Yuen¹, Y Tanaka², N Shinkai², R T Poon³, D Yiu-Kuen But¹, D Y-T Fong⁴, J Fung¹, D Ka-Ho Wong¹, J Chi-Hang Yuen¹, M Mizokami² and C-L Lai¹

¹ Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
² Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
³ Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong
⁴ Department of Nursing Studies, The University of Hong Kong, Queen Mary Hospital, Hong Kong

Correspondence to:
Dr M F Yuen, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong; mfyuen{at}hkucc.hku.hk

Background/aim: To examine the risks for hepatocellular carcinoma (HCC) with respect to hepatitis B virus (HBV) genotypes, specific viral mutations (MT), serum HBV DNA levels, and cirrhosis.

Methods: HBV genotypes, 1653/1753/core promoter (CP)/precore MT and HBV DNA levels were determined in 248 HBV patients with HCC and 248 HBV controls.

Results: Genotype C, CP-MT, T1653, HBV DNA levels 4 log₁₀ copies/ml and cirrhosis had a higher risk for HCC compared to patients with genotype B (p = 0.001, OR 1.9), CP wild-type (WT) (p<0.001, OR 4.1), C1653 (p = 0.028, OR 2.4), HBV DNA <4 log₁₀ copies/ml (p = 0.003, OR 2.1) and without cirrhosis (p<0.001, OR 4.0) respectively. Multivariate analysis showed that CP-MT, T1653, HBV DNA 4 log₁₀ copies/ml and cirrhosis were independent factors for HCC (all p<0.05). A receiver operating characteristics curve showed no cut-off HBV DNA level associated with minimal chance of HCC. Patients with CP-MT and cirrhosis had a 22.2-fold increased risk of HCC compared to patients with CP-WT and without cirrhosis. Patients with CP-MT and HBV DNA levels 4 log₁₀ copies/ml had a 7.2-fold increased risk of HCC compared to patients with CP-WT and HBV DNA levels <4 log₁₀ copies/ml. Patients with CP-MT and T1653 had a 9.9-fold increased risk of HCC compared to patients with wild-type for both regions.

Conclusions: CP-MT, T1653, HBV DNA levels 4 log₁₀ copies/ml and cirrhosis are independent factors for development of HCC. The risks increased substantially in patients having these factors in combination.

Keywords: HBV genotype; core promoter/precore mutations; HBV DNA; T1653; hepatocellular carcinoma

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