Prevalence and Profile of Nonalcoholic Fatty Liver Disease in Lean Adults: Systematic Review and Meta-Analysis

Abstract

Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.

Fig. 1

Prevalence of lean NAFLD. (A) Pooled prevalence of lean NAFLD, (B) population prevalence of lean NAFLD, (C) prevalence of lean NAFLD among all NAFLD, and (D) population prevalence of lean NAFLD among all NAFLD. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 2

Pooled data on liver biochemical markers of subjects with obese NAFLD versus those with lean NAFLD. (A) ALT, (B) albumin, (C) hemoglobin, (D) creatinine, (E) uric acid, and (F) liver stiffness measurement. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 3

Pooled data on liver chemistry and biochemical markers of subjects with lean NAFLD versus healthy subjects. (A) ALT, (B) ALP, (C) total bilirubin, (D) creatinine, (E) CRP, and (F) uric acid. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 4

Pooled data on metabolic syndrome and its components in subjects with obese versus lean NAFLD. (A) Central obesity, (B) hypertension, (C) type 2 diabetes mellitus, (D) impaired fasting glucose, (E) low HDL, and (F) metabolic syndrome. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 5

Pooled data on metabolic syndrome components and genetics in subjects with lean NAFLD versus healthy subjects. (A) Central obesity, (B) hypertension, (C) type 2 diabetes mellitus, (D) low HDL, (E) metabolic syndrome, and (F) PNPLA3. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 6

Pooled data on liver histology comparing obese NAFLD versus lean NAFLD. Odds for (A) hepatocyte ballooning, (B) lobular inflammation, (C) NASH, and (D) fibrosis stage ≥3. The graph represents effect size from each study and black square represents the pooled effect size.

Fig. 7

Pooled data on clinical outcomes comparing lean versus obese NAFLD. The forest plot compares patient survival. The table shows other outcomes for liver‐related mortality, cardiovascular‐related mortality, and liver decompensation. The graph represents effect size from each study and black square represents the pooled effect size. Abbreviations: CV, cardiovascular; NA, not applicable.