Nonalcoholic fatty liver disease in lean subjects: Prognosis, outcomes and management

Table 2 Main findings and outcomes of lean (or non-obese) non-alcoholic fatty liver disease patients’ vs obese ones

Ref./Year/Country	Population (lean/non-obese NAFLD patients)	Metabolic profile, lean/non-obese NAFLD vs non-lean/obese NAFLD	Liver function tests findings, lean/non-obese NAFLD vs non-lean/obese NAFLD	Histological outcomes, lean/non-obese NAFLD vs non-lean/obese NAFLD	Survival-related outcomes, lean/non-obese NAFLD vs non-lean/obese NAFLD
Younossi et al[28]/2012/United States	11613 study population; 2491 NAFLD patients (431 lean)	↓ Prevalence of insulin resistance, T2DM, hypocholesteremia, hypertension, HOMA score	↓ AST, ALT	NA	NA
Zou et al[30]/2020/ United States	4711 patients with NAFLD (1528 non-obese)	Similar prevalence of T2DM and MetS, Metabolic comorbidities: More common	NA	↑ Prevalence of advanced liver fibrosis	↑ 15-yr overall, cardiovascular, cancer and other causes related mortality (not significant in a Cox model)
Yoshitaka et al[31]/2017/Japan	1647 individuals; 312 NAFLD patients (69 non-overweight)	↓ BP, glucose, ↑ HDL-C	↓ AST, ALT, and γ-GT	NA	NA
Kwon et al[38]/2012/South Korea	29994 study population; 6039 NAFLD patients (3014 non-obese)	↑ Prevalence ratios for high BP, glucose intolerance, and ↑ TG, ↓ HDL-C especially among women population	NA	NA	NA
Feng et al[39]/2014/China	1779 study population; 898 NAFLD patients (134 lean)	↓ Insulin, TC, UA, HOMA-IR, ↑ HDL-C	↓ ALT and γ-GT	NA	NA
Lee et al[40]/2018/China	2008 enrolled subjects; 493 NAFLD patients (208 non-obese)	↑ Prevalence of MetS and hypertension, ↓HDL-C	NA	NA	NA
Zeng et al[41]/2020/China	2715 enrolled participants; 1100 NAFLD patients (142 lean)	↑ Prevalence of MetS	NA	Less severe hepatic steatosis, evaluated by ameliorated values of CAP and FLI	NA
Wang et al[43]/2015/China	9360 women population; 1194 were NAFLD patients (514 non-obese)	↑ UA, glucose	↓ ALT, AST but ↑ AST/ALT ratio	NA	NA
Kumar et al[44]/2013/India	205 NAFLD patients (27 lean)	↓ Hyperinsulinemia, HOMA-IR, ↓ prevalence of T2DM, MetS		↓ Mean NAS and ↓ proportion of patients with liver fibrosis	NA
Feldman et al[47]/2017/Austria	187 subjects; 116 NAFLD patients (55 lean)	↓ Glucose, insulin, HOMA-IR, ↑ HDL-C, adiponectin	↓ ALT	NA	NA
Fracanzani et al[49]/2017/Italy	669 NAFLD patients (143 lean)	↓ Prevalence of hypertension, T2DM, MetS, NASH, carotid plaques and significant thinner carotid intima-media	NA	↓ Prevalence of NAFLD and ↓ median NAS	NA
Shao et al[50]/2020/China	534 NAFLD patients (240 non-obese)	No ↑ risk of cardiovascular damage and ↑ TC, FFA, TG, BP, insulin resistance	↓ ALT and AST	NA	NA
Li et al[51]/2019/China	496 NAFLD patients (101 lean)	↑ Proportion of patients with ↑ TG, glucose	↓ Proportion of patients with ↑ ALT	NA	NA
Leung et al[52]/2017/Hong-Kong	307 NAFLD patients (72 non-obese)	↓ Prevalence of MetS, hypertension	NA	↓ NAS, ↓ fibrosis stage, serum cytokeratine-18 fragments and liver stiffness measurement	Severe clinical outcomes (6 deaths, 2 HCC,1 liver failure) were observed only in the obese group
Niriella et al[53]/2018/Sri Lanka	2985 initial cohort; 936 NAFLD patients (120 lean)	↓ Prevalence of hypertension and central obesity, no significant difference in prevalence of other metabolic comorbidities at baseline. No remarkable alterations of new onset of metabolic comorbidities at the completion of follow-up	NA	NA	NA
Honda et al[54]/2016/Japan	1562 enrolled subjects; 540 NAFLD patients (134 non-obese)	↑ HOMA-IR, glucose, insulin, TG, ↓ genotype prevalence of (PNPLA3) GG	↓ ALT and AST	↓ Lobular inflammation, steatosis grade, hepatocyte ballooning and NAS	NA
Wei et al[55]/2015/Hong-Kong	262 patients with NAFLD (135 non-obese)	↓ Insulin resistance, BP and cytokeratin-18 fragments and ↓ prevalence of MS, ↑ genotype (PNPLA3) GG prevalence	NA	Less non-obese NAFLD patients with ↑ NAFLD fibrosis score	NA
Alam et al[56]/2014/Bangladesh	465 NAFLD patients (119 non-obese)	Similar prevalence of T2DM and hypertension and ↓ TC, glucose, HOMA-IR, ↑ HDL-C	↓ ALT, AST, γ-GT	No significant difference in histological findings	NA
Akyuz et al[57]/2015/Turkey	483 NAFLD patients (37 lean)	↓ BP, ↓ prevalence of MetS, less severe hepatic steatosis, ↑ hemoglobin levels	NA	Less severe hepatic fibrosis	NA
Cruz et al[58]/2014/United States	1090 NAFLD patients (125 lean)	↓ Insulin resistance, ↓ prevalence of low HDL-C, hypertriglyceridemia and hypertension	↓ ALT	↓ Steatosis degree and less advanced fibrosis	↓ Cumulative survival
Hagström et al[59]/2018/Sweden	646 NAFLD patients (123 lean, 335 overweight, 188 obese)	↓ TG, glucose	↓ ALT, AST compared to both overweight and obese counterparts	↓ Prevalence of NASH and ↓ mean fibrosis stage compared to both overweight/obese patients	↓ Risk for overall mortality, ↑ risk for severe hepatic disease development as compared to overweight patients

NAFLD: Non-alcoholic fatty liver disease; ALT: Alanine aminotransferase; T2DM: Type 2 diabetes mellitus; BP: Blood pressure; MetS: Metabolic syndrome; TC: Total cholesterol; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; TG: Triglycerides; UA: Uric acid; NASH: Non-alcoholic steatohepatitis; NAS: NAFLD activity score; HOMA-IR: Homeostasis Model Assessment Insulin Resistance; HCC: Hepatocellular carcinoma; CAP: Controlled attenuation parameter; FLI: Fatty liver index; HR: Hazard ratio; PNPLA 3: Patatin-like phospholipase domain-containing protein 3; NA: Not applicable; AST: Aspartate aminotransferase; γ-GT: γ-Glutamyl transferase; MetS: Metabolic syndrome.