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Abstract
Background Emerging research indicates that individuals carrying excess weight experience similar or even higher survival rates in non-alcoholic fatty liver disease (NAFLD) compared to their normal-weight counterparts. This puzzling ‘obesity paradox’ might be attributed to underlying biases. To delve into this phenomenon, we examined data extracted from the third National Health and Nutrition Examination Survey (NHANES) III spanning 1988-1994.
Methods We specifically targeted participants diagnosed with NAFLD through ultrasound due to fatty liver presence and employed multivariate Cox regression to assess mortality risk associated with body mass index (BMI) and waist-to-height ratio (WHtR).
Results Over a median follow-up period of 20.3 [19.9-20.7] years, 1832 participants passed away. The study uncovered an intriguing ‘obesity-survival paradox’ wherein individuals classified as overweight (HR 0.926, 95% CI 0.925 – 0.927) and obese (HR 0.982, 95% CI 0.981 – 0.984) exhibited reduced mortality risks compared to those categorized as normal weight. However, this paradox vanished upon adjustments for smoking and exclusion of the initial 5-year follow-up period (HR 1.046, 95% CI 1.044 – 1.047 for overweight; HR 1.122, 95% CI 1.120 – 1.124 for obesity class I) (IDDF2024-ABS-0180 Figure 1). Notably, the paradox was less pronounced with WHtR, showing significant differences only in quartile 2 (HR 0.982, 95% CI 0.981 – 0.984) when compared to quartile 1, and resolved after appropriate adjustments (IDDF2024-ABS-0180 Figure 2). Of particular significance, when jointly considering BMI and WHtR, higher levels of adiposity indicated a greater risk of mortality with WHtR, whereas BMI did not demonstrate the same trend (p <0.05) (IDDF2024-ABS-0180 Figure 3).
Conclusions The ‘obesity paradox’ in NAFLD was explained by smoking and reverse causation. WHtR was a better predictor of mortality than BMI.