We obtained data on CHB patients who had been diagnosed with malignant liver tumors and underwent curative partial hepatectomy by open or laparoscopic hepatectomy in the first hospital of China Medical University between 2011 and 2018. Diagnosis of HCC was based on two types of imaging examinations including liver ultrasound, computed tomography, and magnetic resonance imaging. Diagnosis was further confirmed via analysis of resected specimens.
Inclusion criteria included: (1) first time hepatectomy for HCC, (2) history of CHB with positive hepatitis B surface antigen (HBsAg), (3) no extrahepatic metastasis, and (4) above 18 years old. Exclusion criteria included: (1) data incomplete, (2) history of hepatectomy for liver malignant tumors, (3) history of transcatheter arterial chemoembolization for HCC, (4) history of chemotherapy for HCC, (5) special types of HCC confirmed by resected specimens, (6) a combination of HCC and cholangiocarcinoma, (7) positive hepatitis C surface antibody with increased HCV-RNA loads, (8) secondary malignant tumor of liver. Detailed patient information is shown in Fig. 1. This study was approved and the need for informed consent was waived by the institutional review board of the First Hospital of China Medical University.
All patients were divided into two groups based on their preoperative serum HBV DNA levels: Group 1 included patients with serum HBV DNA levels less than 2000 IU/mL, Group 2 included patients with serum HBV DNA levels ≥2000 IU/mL.
Medical records were collected and included sex, age, history of antiviral therapy, smoking, and alcohol consumption. An alcohol consumption less than 30 g/d for males and 20 g/d for females was defined as moderate alcohol consumption; and an alcohol consumption more than 60 g on one occasion was defined as heavy episodic drinking . Characteristics of liver tumors were carefully recorded, including the number of nodules, the maximum diameter, differentiation, capsule formation, intrahepatic metastasis, satellite nodules, and portal vein tumor thrombosis.
Blood samples were taken after an overnight fasting. Parameters including leukocyte count, hemoglobin, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), serum albumin (ALB), prothrombin time (PT), international normalized ratio (INR), creatinine, alpha-fetoprotein (AFP), HBsAg (upper limit of detection was 250 IU/mL in our laboratory), serum HBV DNA (lower limit of detection was 100 IU/mL in our laboratory), and hepatitis B e antigen (HBeAg) were then evaluated. Data from preoperative ultrasound, computed tomography, and/or magnetic resonance imaging were also collected.
Follow-up and assessment of recurrence
All patients were followed-up once every month or once every 3 months at the outpatient department. Patients with detectable HBV DNA or liver cirrhosis were given antiviral therapy pre- and post-operation. Complete VR was defined as the HBV DNA levels persistently lower than 100 IU/mL. Partial VR was defined as the HBV DNA load decreased by 2 or more log values when compared with the basic viral load. Virological breakthrough was defined as the HBV DNA loads increased by 1 or more log values when compared with the lowest viral load either during the antiviral treatment or redetected during follow-up. Blood samples were taken after an overnight fasting for analysis of liver function, AFP, and HBV DNA levels at every visit. Liver ultrasound, computed tomography, and/or magnetic resonance imaging were taken at the same time to monitor for new lesions in the liver.
Tumor recurrence was defined as (1) new lesions in the liver suspected by liver ultrasound and furthered confirmed by computed tomography or magnetic resonance imaging with or without elevated serum AFP; (2) new lesions in the liver detected by liver ultrasound, computed tomography, or magnetic resonance imaging, and further confirmed in resected specimens.
Continuous variables are presented as mean ± standard deviation or median (interquartile range). Quantitative variables were compared by Student’s t test for continuous variables with a normal distribution or the Mann-Whitney nonparametric U test. Categorical variables were analyzed by Chi-square test and are expressed as numbers and percentages. Recurrence-free survival was calculated by the Kaplan-Meier method and the differences were compared by log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model with stepwise selection of variables. Statistical analysis was performed using IBM SPSS statistics software version 22.0 (IBM, Armonk, NY, USA). A p value < 0.05 was considered statistically significant.
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