Systematic review with meta‐analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease

Summary Background Current evidence suggests that lean and obese patients with nonalcoholic fatty liver disease ( NAFLD ) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of “lean‐ NAFLD .” Indeed, an unanswered question is whether lean ( BMI  ≤ 25 Kg/m 2 ) NAFLD ‐patients are protected from severe histological outcomes. Aim To perform a meta‐analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese‐ NAFLD patients. Methods Through a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients. Results Relative to lean‐ NAFLD , overweight/obese‐ NAFLD patients showed significantly ( P  = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0‐4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis‐ NASH ( OR 0.58 95% CI 0.34‐0.97) was significantly lower in lean‐ NAFLD (n = 322) than in overweight/obese‐ NAFLD (n = 1357), P  = .04. Relative to lean‐ NAFLD , overweight/obese‐ NAFLD patients also have significantly greater NAFLD activity (difference in means ±  SE : 0.58 ± 0.16, P  = .0004) and steatosis (difference in means ±  SE : 0.23 ± 0.07, P  = .002) scores. Conclusions Lean‐ NAFLD patients tend to show less severe histological features as compared to overweight/obese‐ NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long‐term prognosis.