The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

Summary Background Metabolically healthy obesity ( MHO ) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non‐alcoholic fatty liver disease ( NAFLD )‐related outcomes compared with non‐obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD ‐related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross‐sectional study, including 1058 biopsy‐proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL , hypertriglyceridemia, arterial hypertension). Non‐alcoholic steatohepatitis ( NASH ) and significant fibrosis (F2‐F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma ( AIP ) for cardiovascular risk. Results Metabolically healthy ( OR 1.88; P = 0.050) and unhealthy obesity ( OR 3.47: P < 0.0001), and unhealthy non‐obesity ( OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment ( HOMA ), ALT , and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese ( OR 3.89; P = 0.003) and non‐obese patients ( OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT , HOMA , and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 ± 18) than healthy metabolism (95.6 ± 17) ( P = 0.007). AIP was higher in adverse metabolic conditions ( P = 0.0001). Metabolically unhealthy non‐obesity showed higher liver damage ( NASH 55.8% vs 42.4%; P < 0.05; significant fibrosis 31.7% vs 11.4%; P < 0.0001) and cardiovascular risk ( P < 0.0001) than healthy obesity. Conclusions Metabolic unhealthy status showed a greater impact on NASH , significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions.