Socioeconomic conditions, and not genetics alone, predict progression of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology of NAFLD and are believed to contribute to the greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. We cross-sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. Adjusting for age, sex, body mass index (BMI), and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% CI: 1.21-8.76, p=0.019), an effect comparable to that of possessing the PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to non-significance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (OR: 0.39 [95% CI: 0.13-1.16, p=0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an odds ratio of 8.0 (95% CI: 1.91-33.86, p=0.005). Adjusting for education attenuated the effect of both genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors—rather than genes or ethnicity alone—may be driving disease severity within this population. This study reveals the importance of including socioeconomic variables when considering the role of genetics or ethnicity in complex disease