Effects of Genomic Changes in Hepatitis B Virus on Postoperative Recurrence and Survival in Patients with Hepatocellular Carcinoma

Abstract

To determine whether the genomic changes in hepatitis B virus (HBV) affect the clinical outcomes of hepatocellular carcinoma (HCC) in patients with HBV-associated HCC treated with curative surgical resection. A total of 247 patients with HBV-associated HCC were treated with curative surgical resection. They were followed regularly for a median of 30months. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced. The genomic changes such as the G1896A at precore, the A1762T/G1764A at BCP, the C1653T and the T1753V at X gene, and pre-S2 deletion were not significantly associated with postoperative recurrence of HCC or survival of patients after curative resection. However, in univariate analysis, younger age, elevated serum α-fetoprotein level, elevated serum alanine aminotransferase level, larger tumor size, microvascular invasion, and advanced Cancer of the Liver Italian Program stage were closely associated with shorter survival after surgical resection. In multivariate analysis, only microvascular invasion revealed to be an independent risk factor of postoperative recurrence (relative risk [RR] 5.406; P<0.001); the independent risk factors of shorter survival appeared to be infiltrative type (RR 5.110; P=0.032), larger tumor size (RR 1.976; P=0.047), and microvascular invasion (RR 6.118; P<0.001). The postoperative recurrence or survival period may not be affected by the genomic changes at the precore, BCP, X, and pre-S2 regions in HBV of genotype C2 in patients with HBV-associated HCC treated with curative surgical resection. Rather, it may be closely associated with tumor characteristics, such as the size and type of HCC or presence of microvascular invasion.