From famine to NAFLD: long-term association between fetal famine exposure and adult non-alcoholic fatty liver disease.

BACKGROUND: Malnutrition in early life may change the structure and function of the body, which lead to a number of diseases in adulthood. There are very few studies in health examination population about the prevalence of NAFLD (non-alcoholic fatty liver disease) in adulthood after early experiences of malnutrition. METHODS: A total of 4,188 participants were selected as research objects from a large tertiary Class A general hospital in western China. We divided the subjects into four groups based on their ages at the time of exposure to the famine during the era of the Great Chinese Famine. Binary logistic regression models were used to examine the associations of famine exposure with prevalent mild and moderate to severe NAFLD. Model 1 was adjusted for gender and age, while Model 2 further controlled for overweight/obesity, elevated blood glucose, elevated blood pressure and dyslipidemia. RESULTS: Fetal famine exposure was significantly associated with higher prevalence of both mild and moderate to severe NAFLD compared with the non famine-exposed group (P < 0.05). No statistically significant differences were observed in the risk of mild or moderate to severe NAFLD between the early-childhood exposure group, middle-childhood exposure group and the non famine-exposed group (P > 0.05). Sensitivity analyses restricted to the 1959-1961 birth cohort (N = 291) further confirmed the significant association between fetal famine exposure and NAFLD. We also conducted sensitivity analyses using adjacent birth cohorts. In adjacent cohort 1 (born 1955-1958, N = 487), Model 2-adjusted ORs were 1.33 (95%CI: 0.90-1.94) for mild NAFLD and 0.95 (95%CI: 0.63-1.44) for moderate to severe NAFLD versus the non famine-exposed group. For adjacent cohort 2 (born 1963-1966, N = 908), corresponding Model 2 ORs were 1.39 (95%CI: 0.97-1.99) and 1.38 (95%CI: 0.96-2.00) for mild and moderate to severe NAFLD, respectively. These adjacent- cohort sensitivity analyses showed no statistically significant associations between famine exposure and NAFLD (all P > 0.05), supporting the time-window-specific nature of exposure associations. CONCLUSION: Fetal famine exposure may be associated with the development of adult NAFLD.