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

Table 1 Main findings and outcomes of lean (or non-obese) non-alcoholic fatty liver disease patients’ vs lean (or non-obese) healthy individuals

Ref./Year/Country	Population (lean/non-obese NAFLD population)	Metabolic profile lean/non-obese NAFLD vs healthy controls	Liver function tests findings, lean/non-obese NAFLD vs healthy controls	Histological outcomes, lean/non-obese NAFLD vs healthy controls	Survival-related outcomes, lean/non-obese NAFLD vs healthy controls
Younossi et al[28]/2012/United States	11613 study population; 4457 lean subjects (431)	↑ Prevalence of insulin resistance, T2DM, hypercholesterolemia and hypertension		NA	NA
Golabi et al[29]/2019/United States	5375 lean subjects (581)	↑ Prevalence of metabolic comorbidities	NA	NA	↑ Hazard for all-cause and cardiovascular-related mortality
Zou et al[30]/2020/United States	9654 controls (1528)	↑ BP, HOMA-IR, glucose, insulin, TC, LDL-C, TG, ↓ HDL-C	↑ ALT, AST, γ-GT	NA	↑ 15-yr overall, cardiovascular, cancer and other causes-related mortality (not confirmed in Cox model)
Yoshitaka et al[31]/2017/Japan	1647 individuals; 984 non-overweight subjects (69)	↑ BP, glucose, TG, UA, ↓ HDL-C	↑ AST, ALT, γ-GT	NA	↑ HR of CVD incident
Fukuda et al[32]/2016/Japan	4629 participants (2989) in the non-overweight group (139)	↑ Adjusted HR for T2DM, ↑ BP, TC, TG, ↓ HDL-C	↑ ALT, AST, γ-GT	NA	NA
Nishioji et al[33]/2015/Japan	3271 enrolled individuals; 2606 non-obese (511)	↑ BP, TC, TG, HbA1c, glucose	↑ ALT, AST, γ-GT	NA	NA
Kim et al[34]/2018/South Korea	2920 participants; 2119 in non-obese group (420)	↑ HR for T2DM, ↑ TG, TC, LDL-C, ↓ HDL-C	↑ ALT, AST, γ-GT	NA	NA
Sinn et al[35]/2019/South Korea	51463 total population; 21984 lean subjects (2262)	↑ HR for T2DM onset, ↑ glucose, HbA1c, TG, TC and LDL-C, ↓ HDL-C	↑ ALT and AST	NA	NA
Sung et al[36]/2009/South Korea	30172 all non-obese; (7101)	↑ Prevalence of hypertension, T2DM, MetS in elevated ALT, steatosis and NASH groups	NA	NA	In men: ↑ Cardiovascular risk for group with elevated ALT serum levels and for steatosis and NASH groups. In women: ↑ Cardiovascular risk for steatosis and NASH groups
Kim et al[37]/2013/South Korea	759 individuals (98 in NAFLD group)	↑ Glucose, TG, UA, HOMA-IR, ↓ HDL-C	↑ ALT, AST, γ-GT	NA	NA
Kwon et al[38]/2012/South Korea	29994 study population; 24008 non-obese (3014)	↑ BP, glucose, insulin, HOMA-IR, ↓ HDL-C	↑ AST, ALT, γ-GT	NA	NA
Feng et al[39]/2014/China	1779; 731 in the lean group (134)	↑ OR for hypertension, T2DM, central obesity and MetS, UA, TC, LDL-C, TG, glucose, insulin, HOMA-IR ↓ HDL-C	↑ ALT, AST, γ-GT	NA	NA
Lee et al[40]/2018/China	2008 enrolled subjects; 953 non-obese (208)	↑ TC, TG, glucose	↑ ALT	NA	NA
Zeng et al[41]/2020/China	2715 enrolled participants (1100 NAFLD patients)	↑ Prevalence of hypertension and MetS, TG, LDL-C, ↓ HDL-C	NA	NA	NA
Yu et al[42]/2014/China	1296 non-obese subjects of whom 246 were NAFLD patients	↑ Arterial stiffness, assessed by the higher brachial-ankle pulse wave velocity, TC, LDL-C, TG, glucose, insulin, UA, HOMA-IR	↑ ALT, AST	NA	NA
Wang et al[43]/2015/China	9360 women population (1194 were NAFLD patients)	↑ TG, TC, LDL-C, glucose	↑ AST, ALT	NA	NA
Kumar et al[44]/2013/India	205 NAFLD patients (27 lean) plus 131 lean healthy subjects	↑ Prevalence of MetS, dyslipidemia		NA	NA
Oral et al[45]/2019/Turkey	367 non-obese individuals (225 in NAFLD group and 142 in the control group)	↑ TG, TC, UA, creatinine, HOMA-IR	↑ AST, ALT	NA	NA
Erkan et al[46]/2014/Turkey	219 non-obese non diabetic individuals of whom 143 NAFLD patients	↑ Prevalence of hypertension, MetS, hyperglycemia, hypertriglyceridemia and insulin resistance, insulin, HOMA-IR	↑ AST, ALT, γ-GT	NA	NA
Feldman et al[47]/2017/Austria	187 subjects (116 suffering from NAFLD of whom 55 were lean)	↑ Prevalence of T2DM, glucose, ↓ adiponectin	↑ ALT, γ-GT	NA	NA
Gonzalez-Cantero et al[48]/2018/Spain	113 non-obese enrolled individuals (55 NAFLD patients)	↑ HOMA-IR, TG, insulin, ↓ HDL-C, adiponectin	↑ ALT, AST, γ-GT	NA	NA

NAFLD: Non-alcoholic fatty liver disease; ALT: Alanine aminotransferase; T2DM: Type 2 diabetes mellitus; NASH: Non-alcoholic steatohepatitis; NAS: NAFLD activity score; BP: Arterial blood pressure; TC: Total cholesterol; LDL-C: Low density lipoprotein-cholesterol; HDL-C: High density lipoprotein-cholesterol; TG: Triglycerides; HR: Hazard ratio; HbA1c: Glycosylated hemoglobin, type A1C; HOMA-IR: Homeostasis Model Assessment Insulin Resistance; CVD: Cardiovascular disease; HCC: Hepatocellular carcinoma; NA: Not applicable; UA: Uric acid; AST: Aspartate aminotransferase; γ-GT: γ-Glutamyl transferase; MetS: Metabolic syndrome.