Pathogenesis from Inflammation to Cancer in NASH-Derived HCC

Simiao Yu,1,* Jingxiao Wang,2,* Haocheng Zheng,3,* Ruilin Wang,4,* Nadia Johnson,1 Tao Li,3 Ping Li,1 Jie Lin,5 Yuan Li,5 Jin Yan,6 Ying Zhang,6 Zhenyu Zhu,6 Xia Ding3,7 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Department of Hepatology of Traditional Chinese Medicine, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 5National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 6Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 7Centre of Research for Traditional Chinese Medicine Digestive, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xia Ding, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Email dingx@bucm.edu.cn Zhenyu Zhu, Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Email zhuzy302@163.comAbstract: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the deadliest cancers worldwide. As opposed to the majority of patients with HCC, approximately 20– 30% of cases of non-alcoholic steatohepatitis (NASH)-derived HCC develop malignant tumours in the absence of liver cirrhosis. NASH is characterized by metabolic dysregulation, chronic inflammation and cell death in the liver, which provide a favorable setting for the transformation of inflammation into cancer. This review aims to describe the pathogenesis and the underlying mechanism of the transition from inflammation to cancer in NASH.Keywords: non-alcoholic steatohepatitis, hepatocellular carcinoma, inflammation to cancer transition, metabolic dysregulation, immune microenvironment