Hepatitis B Surface Antigen As A New Marker Predict Hepatitis B Virus-related Hepatocellular Carcinoma Recurrence Following Curative Resection In Patients With Low HBV Load

Background and aimsPatients with high levels of hepatitis B surface antigen (HBsAg) have a high risk fordeveloping hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However,little is known about whether higher levels of HBsAg increase risk of HCC recurrencefollowing curative resection. Herein we aimed to investigate the association betweenpreoperative HBsAg level and risk of HCC recurrence following curative resection.MethodsFrom October2009to August2010, consecutively826HBV-related HCC patients whounderwent curative resection in Eastern Hepatobiliary Surgery Hospital (Shanghai, China)were enrolled. Serum HBsAg levels were analyzed for association with HCC recurrence,together with other clinical variables.ResultsDuring a follow-up of35.8±9.9months,395patients had HCC recurrence. Univariateanalysis revealed that HBeAg seropositivity, and higher levels of ALT, serum HBsAg, andHBV viral load were associated with a higher cumulative incidence of HCC recurrence. Inaddition, other risk factors, including aspartate aminotransferase (AST)>37U/L,γ-glutamyl transpeptidase (GT)>61U/L, alkaline phosphatase (ALP)>129U/L,prothrombin time (PT)>13s, AFP>20μg/L, multinodularity, larger tumor size, cuttingmargin≥1cm, no capsule formation, portal vein invasion, microvascular invasion, andhigher rank of Edmonson grading and pTNM stage were found to be associated with HCCrecurrence. Multivariate analyses showed that serum HBsAg≥2000S/CO (HR:1.538,95.0%CI:1.054-2.243, p=0.026), seropositive hepatitis B e antigen (HBeAg)(HR:1.424,95.0%CI:1.052-1.928, p=0.022), γ-glutamyl transpeptidase>61U/L (HR:1.561,95.0%CI: 1.164-2.093, p=0.003), prothrombin time>13s (HR:1.451,95.0%CI:1.047-2.011,p=0.025), multinodularity (HR:1.621,95.0%CI:1.183-2.222, p=0.003), lager tumor size(HR:1.219,95.0%CI:1.044-1.424, p=0.012), and major portal vein invasion(HR:1.832,95.0%CI:1.184-2.836, p=0.007) were independently associated with a increased risk ofHCC recurrence. Compared with HCC patients with HBsAg level<2000S/CO, HCCpatients with HBsAg level≥2000S/CO had a higher prevalence of seropositive HBeAg,antiviral therapy, and cirrhosis; were younger; and had a higher levels of alaninetransarninase (ALT), aspartate aminotransferase (AST), and HBV viral load. Multivariablestratified analyses showed HCC patients with HBsAg level≥2000S/CO tended to have ahigher incidence of HCC recurrence in these subgroups of patients, including fornoncirrhotic, HBV DNA<2000IU/mL, ALT≤41U/L, AST≤37U/L, and seronegativeHBeAg. When we evaluated HBeAg-negative patients with HBV DNA <2000IU/mL,HBsAg level still determined risk of HCC recurrence (p=0.014), but not HBV DNA(p=0.550) and ALT (p=0.186).ConclusionsHigh levels of HBsAg increase risk of HCC recurrence following curative resection.HBsAg level might complement HBV DNA level in predicting HCC recurrence, especiallyin HBeAg-negative patients with low viral load.