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    The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention. Liu Zhenqiu,Jiang Yanfeng,Yuan Huangbo,Fang Qiwen,Cai Ning,Suo Chen,Jin Li,Zhang Tiejun,Chen Xingdong Journal of hepatology BACKGROUND & AIMS:Liver cancer is a common malignant neoplasm worldwide. The etiologies for liver cancer are diverse and the incidence trends of liver cancer caused by specific etiologies are rarely studied. We therefore aimed to determine the pattern of liver cancer incidence, as well as temporal trends. METHODS:We collected detailed information on liver cancer etiology between 1990-2016, derived from the Global Burden of Disease study in 2016. Estimated annual percentage changes (EAPCs) in liver cancer age standardized incidence rate (ASR), by sex, region, and etiology, were calculated to quantify the temporal trends in liver cancer ASR. RESULTS:Globally, incident cases of liver cancer increased 114.0% from 471,000 in 1990 to 1,007,800 in 2016. The overall ASR increased by an average 0.34% (95% CI 0.22%-0.45%) per year in this period. The ASR of liver cancer due to hepatitis B, hepatitis C, and other causes increased between 1990 and 2016. The corresponding EAPCs were 0.22 (95% CI 0.08-0.36), 0.57 (95% CI 0.48-0.66), and 0.51 (95% CI 0.41-0.62), respectively. The ASR of liver cancer due to reported alcohol use remained stable (EAPC = 0.10, 95% CI -0.06-0.25). This increasing pattern was heterogeneous across regions and countries. The most pronounced increases were generally observed in countries with a high socio-demographic index, including the Netherlands, the UK, and the USA. CONCLUSIONS:Liver cancer remains a major public health concern globally, though control of hepatitis B and C virus infections has contributed to the decreasing incidence in some regions. We observed an unfavorable trend in countries with a high socio-demographic index, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in liver cancer. LAY SUMMARY:Liver cancer is a common malignant neoplasm worldwide. The incidence patterns of liver cancer caused by different etiologies varied considerably across the world. In this study, we aim to determine the pattern of liver cancer incidence as well as the temporal trends, thereby facilitating the establishment of more tailored prevention strategies for liver cancer. 10.1016/j.jhep.2018.12.001
    Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer. Ma Lichun,Hernandez Maria O,Zhao Yongmei,Mehta Monika,Tran Bao,Kelly Michael,Rae Zachary,Hernandez Jonathan M,Davis Jeremy L,Martin Sean P,Kleiner David E,Hewitt Stephen M,Ylaya Kris,Wood Bradford J,Greten Tim F,Wang Xin Wei Cancer cell Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis. 10.1016/j.ccell.2019.08.007