Published online Jun 28, 2013. doi: 10.3748/wjg.v19.i24.3861
Revised: April 12, 2013
Accepted: May 7, 2013
Published online: June 28, 2013
Processing time: 142 Days and 6.2 Hours
AIM: To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.
METHODS: We investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ2 test and unconditional logistic regression analysis.
RESULTS: In the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ2 = 15.441, P = 0.000; χ2 = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264).
CONCLUSION: Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.
Core tip: YMDD mutation is a research hotspot globally. Until recently, most research about YMDD mutation focused on the occurrence of lamivudine-related YMDD mutation and its impact on antiviral treatment. In our research, 264 hepatitis B virus (HBV)-related liver cirrhosis patients not treated with antiviral drugs, including 81 with primary hepatocellular carcinoma (HCC), were investigated for the association between infection by different HBV genotype strains with spontaneous YMDD mutations and occurrence of primary HCC in cirrhosis patients. Infection by genotype C strains with spontaneous YMDD mutations is an independent risk factor for the development of HCC in cirrhosis patients.