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The Greater Mekong Subregion (GMS) is a trans-national region of the Mekong River basin in Southeast Asia comprising Cambodia, the People's Republic of China (specifically Yunnan Province and Guangxi Zhuang Autonomous Region), Lao People's Democratic Republic (Lao PDR), Myanmar, Thailand, and Vietnam home to more than 340 million people or almost 4.5% of the global population. Human liver fluke infections caused by Opisthorchis viverrini and Clonorchis sinensis have been major public health problems in this region for decades. Opisthorchiasis caused by O. viverrini is prevalent in Thailand, Lao PDR, Cambodia and central-southern Vietnam with more than 12 million people infected. Clonorchiasis caused by C. sinensis is endemic in northern Vietnam and Guangxi with estimated 3.5 -5 million infected. The infections can cause several liver and biliary diseases such as cholangitis, periductal fibrosis, gallstones, and cholangiocarcinoma (CCA), a fatal bile duct cancer. Key determinants of the geographical distribution differences of the two liver fluke species are snail species and geographic barriers. Main risk behaviour of the infections is the culture of eating raw fish "the raw attitude" of people in the GMS, especially the Tai/Dai/Thai/Laos ethnic groups, the major population in the GMS. Over the past 20 years, there is a big change in prevalence of the infections. Opisthorchiasis has long been endemic, particularly in northern and northeastern Thailand and Lao PDR with over 8-10 million cases estimated. However, after several rounds of national campaign against opisthorchiasis using integrated control approach in Thailand over the past three decades, the prevalence of O. viverrini infection has reduced from over 15% in 1996 to 2.2% in 2019. High prevalence of O. viverrini infection continues in Lao PDR and central Vietnam. Emerging high prevalence, up to a maximum of 47.5%, has been noted in Cambodia during the past 10 years possibly due to more studies being conducted rather than increasing prevalence. O. viverrini infection has now also been reported in Lower Myanmar in recent years. Clonorchiasis has been known in northern Vietnam and southern China for a long time. Several surveys have reported infections in Guangxi in the last 10 years, and until now liver fluke infected cases have not been reported in Yunnan. Overall, nowadays, there is a shift in high risk areas for GMS liver fluke infection from northeastern Thailand to Lao PDR, Cambodia, Vietnam, Myanmar, and Guangxi P.R. China. Urgent systematic disease mapping and integrated liver fluke control using One Health approaches should be implemented nationwide in GMS countries., (Copyright © 2021 Elsevier B.V. All rights reserved.)