Heavy metals are liver fibrosis risk factors in people without traditional liver disease etiologies

Liver fibrosis is an important predictor of mortality. Liver disease case definitions changed in 2023. These definitions include an easily over-looked group with no traditional etiology (NTE) of liver disease and no steatosis. We analyzed heavy metals and cardiometabolic risk factors (CMRFs) as fibrosis risk factors in the NTE group and in people with another newly-defined condition, metabolic dysfunction-associated steatotic liver disease (MASLD). Two National Health and Nutrition Examination Survey (NHANES) datasets were analyzed. In NHANES III (1988-1994), fibrosis and steatosis were defined by Fibrosis-4 scores and ultrasound, respectively, in 12,208 adults. In NHANES 2017-2020, fibrosis and steatosis were defined by transient elastography and the controlled attenuation parameter (CAP) in 5525 adults. Fibrosis risk factors varied over time and by race/ethnicity. In the earlier dataset, NTE-fibrosis had a positive, non-significant, association with high blood levels of lead (Pb). MASLD-fibrosis was associated with Pb (OR = 2.5, 95 % CI, 1.4-4.4) and not with CMRFs in non-Hispanic Blacks but was associated with CMRFs in non-Hispanic Whites. Heavy metal exposures fell between the two time periods. In the later dataset, NTE-fibrosis was associated with Pb (OR = 4.2, 95 % CI, 2.6-6.8) and cadmium (OR = 1.8, 95 % CI, 1.1-3.0) in the total population, but not with most CMRFs. MASLD-fibrosis was strongly-significantly associated with CMRFs in every racial/ethnic group except non-Hispanic Blacks in whom CMRFs were only weakly associated with MASLD-fibrosis. Heavy metal pollution, which disproportionately impacts minoritized populations, decreased over time, but remained strongly associated with liver fibrosis in people lacking traditional etiological factors for liver disease.