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Dig Dis Sci. 2016 May;61(5):1226-33. doi: 10.1007/s10620-016-4095-4. Epub 2016 Mar 22.

Natural History of Nonalcoholic Fatty Liver Disease.

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Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.
Duke-NUS Graduate Medical School, Singapore, Singapore.
Department of Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue/A30, Cleveland, OH, 44195, USA.
Department of Pathobiology, Cleveland Clinic Foundation, Cleveland, OH, USA.


Nonalcoholic fatty liver disease (NAFLD) remains among the most common liver diseases worldwide, with increasing prevalence in concert with the obesity and metabolic syndrome epidemic. The evidence on the natural history, albeit with some ambiguity, suggests the potential for some subsets of NAFLD to progress to cirrhosis, liver-related complications and mortality with fibrosis being the most important predictor of hard long-term endpoints such as mortality and liver complications. In this setting, NAFLD proves to be a formidable disease entity, with considerable clinical burden, for both the present and the future. Our understanding of the natural history of NAFLD is constantly evolving, with nascent data challenging current dogma. Further clarification of the natural history is required with well-designed, well-defined studies using prospectively collected data. Identifying the predictors of long-term outcomes should be used to direct development of clinical trial endpoints in NAFLD.


Fibrosis; Natural history; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Prevalence; Steatosis

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