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Lei Liang,1,2,* Ming-Da Wang,3,* Yao-Ming Zhang,4 Wan-Guang Zhang,5 Cheng-Wu Zhang,1 Wan Yee Lau,3,6 Feng Shen,3 Timothy M Pawlik,7 Dong-Sheng Huang,1,2,8 Tian Yang1– 3,8 1Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, People's Republic of China; 2School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People's Republic of China; 3Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People's Republic of China; 4The 2nd Department of Hepatobiliary Surgery, Meizhou People's Hospital, Guangdong, People's Republic of China; 5Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China; 6Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China; 7Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA; 8The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People' s Hospital (People' s Hospital of Hangzhou Medical College), Hangzhou, People's Republic of China*These authors contributed equally to this workCorrespondence: Tian YangDepartment of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, 310014, People's Republic of ChinaEmail yangtiandfgd@hotmail.comDong-Sheng HuangDepartment of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, 310014, People's Republic of ChinaEmail Huangdongshengsj@hotmail.comBackground: High alpha-fetoprotein (AFP) expressions (> 400 ng/mL) are associated with poor oncological characteristics for hepatocellular carcinoma (HCC). However, prognosis after liver resection for high-AFP HCC is poorly studied. To investigate long-term recurrence and survival after hepatectomy for high-AFP HCC, and to identify the predictive value of postoperative incomplete biomarker response (IBR) on overall survival (OS) and recurrence-free survival (RFS).Methods: Patients undergoing curative resection for high-AFP HCC were analyzed. According to the decline magnitude of serum AFP as measured at first follow-up (4∼ 6 weeks after surgery), all patients were divided into the complete biomarker response (CBR) and IBR groups. Characteristics, recurrence, and survival rates were compared. Univariate and Multivariate Cox-regression analyses were performed to identify independent predictors associated with poorer OS and RFS after liver resection for high-AFP HCC.Results: Among 549 patients, the overall and early recurrence rates in patients with IBR were significantly higher than patients with CBR (97.8%vs.56.4%, and 92.5%vs.33.3%, both P< 0.001). On multivariate analysis, postoperative IBR was the strongest risk factor with the highest hazard ratio in predicting poor OS (HR 2.97; 95% CI 2.49∼ 3.45; P< 0.001) and RFS (HR 4.29; 95% CI 3.31∼ 5.55; P< 0.001).Conclusion: Postoperative biomarker response of serum AFP can be used in predicting recurrence and survival for high-AFP HCC patients. Once postoperative IBR was identified at first follow-up, subsequent enhanced recurrence surveillance and available treatments against recurrence should actively be considered.Keywords: hepatocellular carcinoma, alpha-fetoprotein, hepatectomy, survival, recurrence

IMPORTANCE: A reduced incidence of microvascular invasion (MVI) in hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) may be associated with a decreased risk of early tumor recurrence and better survival after partial hepatectomy. OBJECTIVE: To examine the association of preoperative antiviral treatment (AVT) with the incidences of MVI and posthepatectomy early tumor recurrence in HBV-related HCC. DESIGN, SETTING, AND PARTICIPANTS: Data on a cohort of 2362 patients who underwent R0 resection for HBV-related HCC between January 2008 and April 2010 at the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, were reviewed. The median (interquartile range) postoperative follow-up was 44.8 (22.8-59.3) months. Data were analyzed from June 2016 to October 2017. INTERVENTIONS: Preoperative AVT and partial hepatectomy. MAIN OUTCOMES AND MEASURES: Overall survival and time to recurrence after surgery were calculated and compared using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Independent risk factors of MVI presence were assessed by logistic regression analysis. RESULTS: Among 2362 included patients, 1999 (84.6%) were men, and the median (interquartile range) age was 50.6 (43.1-57.3) years. A total of 2036 patients (86.2%) did not receive any preoperative AVT, while 326 (13.8%) received ongoing AVT more than 90 days before surgery. In the non-AVT group, compared with a preoperative HBV DNA level of less than 2000 IU/mL, a preoperative HBV DNA level of 2000 IU/mL or greater was associated with an increased risk of MVI (odds ratio [OR], 1.399; 95% CI, 1.151-1.701). Compared with the non-AVT group, patients receiving AVT had a lower incidence of MVI (38.7% [126 of 326] vs 48.6% [989 of 2036]; P = .001) and reduced risk of MVI (OR, 0.758; 95% CI, 0.575-0.998). A complete response to AVT was an independent protective factor of MVI (OR, 0.690; 95% CI, 0.500-0.952). Accordingly, preoperative AVT was associated with decreased 6-month, 1-year, and ...