The autophagy marker LC3 strongly predicts immediate mortality after surgical resection for hepatocellular carcinoma

// Chih-Wen Lin 1, 2, 3, 4 , Chih-Che Lin 6 , Po-Huang Lee 4, 5 , Gin-Ho Lo 2, 4 , Pei-Min Hsieh 5 , Kah Wee Koh 2, 3 , Chih-Yuan Lee 7 , Yao-Li Chen 8 , Chia-Yen Dai 9 , Jee-Fu Huang 9 , Wang-Long Chuang 9 , Yaw-Sen Chen 4, 5, * and Ming-Lung Yu 9, 10, 11, * 1 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan 2 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 3 Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 4 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan 5 Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 6 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 7 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 8 Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan 9 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan 11 Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Ming-Lung Yu, email: fish6069@gmail.com Keywords: albumin, autophagy, liver failure, post-hepatectomy immediate mortality, predictor Received: May 19, 2017      Accepted: June 30, 2017      Published: August 01, 2017 ABSTRACT The remnant liver’s ability to regenerate may affect post-hepatectomy immediate mortality. The promotion of autophagy post-hepatectomy could enhance liver regeneration and reduce mortality. This study aimed to identify predictive factors of immediate mortality after surgical resection for hepatocellular carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their first surgical resection in Taiwan were enrolled between 2010 and 2014. Clinicopathological data and immediate mortality, defined as all cause-mortality within three months after surgery, were analyzed. The expression of autophagy proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by immunohistochemical staining. Approximately 5% of patients had immediate mortality after surgery. The absence of LC3, hypoalbuminemia (<3.5 g/dl), high alanine aminotransferase, and major liver surgery were significantly associated with immediate mortality in univariate analyses. Multivariate logistic regression demonstrated that absence of LC3 (hazard ratio/95% confidence interval: 40.8/5.14-325) and hypoalbuminemia (2.88/1.11-7.52) were significantly associated with immediate mortality. The 3-month cumulative incidence of mortality was 12.1%, 13.0%, 21.4% and 0.4%, respectively, among patients with absence of LC3 expression, hypoalbuminemia, both, or neither of the two. In conclusion, the absence of LC3 expression in adjacent non-tumor tissues and hypoalbuminemia were strongly predictive of immediate mortality after resection for HCC.