Table 2 Characteristics and mortality associated with NAFLD in lean individuals
Study | Country | Agea | BMI | ALT (U/L)a | AST (U/L)a | Metabolic profile and related characteristicsb | Mortality | F/Uc |
|---|---|---|---|---|---|---|---|---|
European/North American | ||||||||
 Younossi et al. [26] | USA | 41.9 ± 1.2 | 22.2 ± 0.16 | 18.0 ± 0.16 | 21.5 ± 0.16 | Younger, female predominance, lower ALT, AST, HOMA score, platelet count, lower frequency of visceral obesity, insulin resistance, T2D, hypercholesteremia, and hypertension | – | – |
 Margariti et al. [29] | Greece | 44 ± 16 | NA | 92 (17–164) | 45 (18–121) | Higher ALT and AST, less comorbidities, smaller waist circumference, lower liver stiffness measures | – | – |
 Cruz et al. [142] | USA | NA | 23.1 ± 1.7 | NA | NA | Male predominance, non-Caucasian, lower ALT levels and HOMA, lower prevalence of T2D, hypertension, hypertriglyceridemia, low-HDL-C, central obesity, and metabolic syndrome, lower degree of steatosis and less advanced fibrosis, more severe lobular inflammation | Higher overall mortality than non-lean NAFLD patients | 11.1 ± 6.8 |
 Feldman et al. [28] | Austria | 61 (12)d | 23.6 (1.8)d | 21.0 (14.0)d | 22.0 (10.5)d | Waist circumference, ALT, GGT, TG, HDL-C, FPG, adiponectin levels, and HOMA-IR intermediate between lean healthy and NAFLD with obesity | – | – |
 Fracanzani et al. [30] | Italy | 46 ± 13 | 23 ± 2 | 64 ± 42 | 41 ± 27 | Less prevalence of hypertension, diabetes, and metabolic syndrome, NASH, fibrosis of F2 or higher, carotid plaques and significantly thinner carotid intima-media | – | – |
 Denkmayr et al. [31] | Austria | 48.7 ± 14.8 | 23.1 ± 1.5 | 60.0 ± 36.4 | 43.0 ± 26.9 | Less components of metabolic syndrome, higher rate of cirrhosis | – | – |
 Bernhardt et al. [161] | Germany | NA | 23.8 (23.0–24.7) | 26.0 ± 7.1 | 26.4 ± 3.0 | Higher serum ferritin, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration, lower levels of soluble transferrin receptor, high HOMA-IR, TC, LDL-C, and TG, comparable to NAFLD patients with obesity | – | – |
 Hagstrom et al. [36] | Sweden | 51.4 ± 13.4 | 23.1 ± 2.7 | 72 ± 47 | 44 ± 25 | Older, lower transaminase levels, lower stages of fibrosis, and lower prevalence of NASH at baseline; increased risk for severe liver disease | Similar overall mortality as non-lean NAFLD patients | 19.9 |
 Golabi et al. [37] | USA | 50.9 ± 1.3 | NA | NA | NA | Older, more likely to be Hispanic, had lower income, and had reported poorer health and more comorbiditiese | Higher risk for all cause and CV mortality compared to lean controls | 17.8 |
 Feldman et al. [162] | Austria | 47.6 ± 14.5 | 23.0 ± 1.5 | 54.6 ± 35.5 | 47.6 ± 24.8 | Higher likelihood of dying from liver-related causes compared NAFLD patients with overweight or obesity; higher proportion with cirrhosis; less features of metabolic syndrome | Similar overall mortality as NAFLD patients with obesity | 8.4 |
 Ahmed et al. [27] | USA | 51.5 ± 18.0 | 22.5 ± 2.0 | NA | NA | Female predominance, higher proportion of Asian and African Americans, lower risk of metabolic comorbidities; same risk of cirrhosis and decompensation, malignancy, and cardiovascular events as non-lean NAFLD patients | Higher risk for all-cause mortality compared to NAFLD patients with obesity | 6.4 |
 Younes et al. [33] | USA | 45 (36, 55)d | 29.8 (26.5, 34.5)d | 59 (41, 88)d | 38 (28, 54)d | Younger, male predominance, less steatosis, lobular inflammation, ballooning and advanced liver fibrosis | Same mortality risk as non-lean NAFLD patients | 7.7 |
Middle Eastern | ||||||||
 Akyuz et al. [144] | Turkey | 41.2 ± 11.8 | 23.6 ± 1.3 | 82 ± 46 | 49 ± 38 | Younger, lower blood pressure, higher hemoglobin, lower prevalence of metabolic syndrome, and less severe hepatic fibrosis | – | – |
 Lankarani et al. [145] | Iran | 49.8 ± 13.9 | NA | NA | NA | Lower waist circumference, TG levels, and prevalence of metabolic syndrome | – | – |
South Asian | ||||||||
 Kumar et al. [147] | India | 38 ± 15.4 | 21.3 ± 1.9 | 45 (11–217) | 38 (23–180) | Similar metabolic profile as overweight group, but lower than obese group, lower prevalence of fibrosis in lean individuals, but similar prevalence of NASH | – | – |
 Bhat et al. [148] | India | 39.9 ± 7.4 | 21.7 ± 1.3 | 69.9 ± 29.8 | NA | Lower HOMA-IR, similar levels of fasting and 2 h glucose and lipid levels | – | – |
 Niriella et al. [108] | Sri Lanka | 35.6 ± 6.4 | NA | NA | NA | Male predominance, lower prevalence of hypertension and central obesity, similar prevalence of other metabolic comorbidities as non-lean group | – | – |
 Choudhary et al. [152] | India | 33.5 ± 10.4 | 21.3 ± 1.2 | 33.4 ± 11.7 | 26.6 ± 7.5 | Younger age, lower ALT, TGs, fasting glucose, LDL-C, higher HDL-C than non-lean group | – | – |
East Asian | ||||||||
 Kim et al. [14] | Korea | 51.6 ± 9.7 | 23.4 ± 1.3 | 31.9 ± 19.0 | 23.5 ± 7.7 | Male predominance, higher BMI, WC, WHR, uric acid, fasting blood glucose, insulin, ASP, ALT, HOMA-IR compared to lean controls; no differences in metabolic variables compared to overweight group | – | – |
 Feng et al. [155] | China | 48.2 ± 10.5 | 22.7 ± 1.1 | 21.6 ± 11.9 | 21.1 ± 9.3 | Male predominance, higher BMI and blood pressure, and greater likelihood of having diabetes, metabolic syndrome, and hypertension compared to lean controls; lower levels of blood glucose, blood pressure, hyperlipidemia, IR, blood cell count and HGB than non-lean NAFLD patients | – | – |
 Fukuda [156] | Japan | 42.6 ± 7.6 | 21.8 ± 0.9 | 25 (19, 36) | 19 (15, 23) | Male predominance, higher incidence of T2D, ALT, AST, HbA1c, FPG, and TG compared to overweight group without NAFLD and lean control group | – | 12.8 |
 Wang et al. [157] | China | 43 (32–58) | 21.6 (20.2–22.8) | 16.1 ± 12.3 | 20.3 ± 8.0 | Male predominance | – | – |
 Yoshitaka et al. [158] | Japan | 50.0 ± 7.9 | 22.0 ± 0.7 | 30.2 ± 15.9 | 21.1 ± 6.1 | Higher blood pressure, triglycerides, fasting plasma glucose, uric acid, ALT, AST, and GGT, lower HDL-C, higher risk of incident CVD relative to lean controls | – | – |
 Shao et al. [159] | China | 44.7 ± 11.9 | 21.6 ± 1.2 | 24 (19, 35) | 25 (20, 32) | Lower WC, WHR, blood pressure, ALT, AST, fasting insulin, HOMA-IR, atherosclerosis index, liver fat content, and liver stiffness compared to nonlean group with NAFLD |  |  |
 Wang [160] | Japan | 45.6 ± 8.3 | 21.7 ± 1.1 | 16.2 ± 11.5 | 17.2 ± 8.4 | Male predominance, older age, higher BMI, WC, smoking status, FPG, HbA1c, TG, blood pressure, hepatic transaminases, and risk of incident T2D, and lower HDL-C compared to lean control group |  |  |
Meta-analyses | ||||||||
 Sookoian and Pirola [34] | Multi | NA | NA | NA | NA | Lower fibrosis score, less risk for NASH, and lower NAFLD activity compared to NAFLD patients with obesity | – | – |