Update in lean metabolic dysfunction-associated steatotic liver disease

Table 1 Characteristics of lean non-alcoholic fatty liver disease patients

Ref.	Population	Prevalence	Characteristics	Cardiometabolic risk	Laboratory values	Anthropometric values
Younossi et al[7], 2012	Compared lean with overweight/obese NAFLD patients (n = 11613)	18%	< 40 yr, female	↓ T2DM, IR, HTN, Hypercholesterolemia	↓ AST, ALT, platelets	Not reported
Wei et al[37], 2015	Compared lean with overweight/obese NAFLD patients (n = 911)	19.3%	< 50 years: male, > 50 years: No difference between sexes	↓ T2DM, HTN, MetS and liver stiffness	↓ ALT, HOMA-IR, ↑ HDL	↓ WC, WHR
Fracanzani et al[66], 2017	Compare lean with overweight/obese NAFLD patients (n = 669)	21.3%	Not reported	↓ T2DM, MetS, HTN	↓ HOMA-IR, ↑ HDL, platelet	↓ WC
Golabi et al[65], 2019	Compare lean with and without NAFLD patients (n = 5375)	Not reported	Not reported	↑ Risk cardiovascular and all-cause of mortality	Not reported	Not reported
Shao et al[63], 2020	Compare lean with obese NAFLD patients (n = 543)	Not reported	No difference between sexes or age	↓ BP	↓ AST, ALT, LDL, total cholesterol, FBG, HOMA-IR, ↑ HDL	↓ BMI, WC, WHR
Aneni et al[40], 2020	Compared lean with and without NAFLD patients (n = 9137)	3.8%	> 40 yr, male	↑ Risk of AD, BP	↑ FBG, total cholesterol, LDL, TG, AST, ALTl; Low HDL	↑ WC
Rahman et al[41], 2020	Compared lean with and without NAFLD patients (n = 1305)	4.4%	> 40 yr, male	↑ MetS, T2DM	↑ TG, Total cholesterol, FBG	↑ Abdominal obesity, BMI
Semmler et al[46], 2021	Compared lean with and without NAFLD patients (n = 3043)	6.7%	> 40 yr, male	↑ Dyslipidemia, IR, T2DM, MetS, cardiovascular risk	Not reported	↑ WC
Weinberg et al[60], 2021	Compared lean with overweight/obese NAFLD patients (n = 3386)	Not reported	> 60 yr No difference between sexes	↓ Cirrhosis, CVD, HTN, T2DM, dyslipidemia	↓ AST, ALT; ↑ Albumin	Not reported
Aneni et al[58], 2022	Compared lean with overweight/obese NAFLD patients (n = 6513)	Not reported	< 45 yr, female	↓ HTN, T2DM, hyperlipidemia, MetS, AD, ↑ risk of all-cause of mortality	↓ FBG, total cholesterol, LDL, TG, AST, ALT; ↑ HDL	↓ WC
Razouki et al[45], 2022	Describe lean NAFLD (n = 1049)	5.8%	> 60 yr, male, Asian American	↑ MetS, Inadequate physical activity	↑ FBG, TG
Zhang et al[56], 2022	Compare lean with obese NAFLD patients (n = 2708)	34.1%	> 40 yr	↓ BP	↓ HOMA-IR; ↑ HDL	↓ WC
Ahmed et al[50], 2022	Compared lean with overweight/obese NAFLD patients (n = 4834)	8.6%	Females, Asian and African American	↓ HTN, T2DM, hyperlipidemia	Not reported	Not reported
Nabi et al[42], 2023	Compared lean with non-lean NAFLD patients (n = 25753)	5.3%	< 40 yr, no difference between sexes	↑ Risk of CVD, liver-related events, CKD and all-cause of death	↑ AST	↓ WC
De et al[52], 2023	Compared lean with non-lean NAFLD patients (n = 1040)	14.3%	No difference between sexes and age	↓ HTN, MetS	No significant difference	↓ Central obesity
Wijarnpreecha et al[62], 2023	Compared lean with non-lean NAFLD patients (n = 18594)	11.4%	Female, no difference between age	↓ MetS, HTN, T2DM, CKD, cerebrovascular accident	↓ AST, ALT, total cholesterol, LDL and TG, ↑ HDL	Not reported
Biswas et al[59], 2023	Compared lean with overweight/obese NAFLD patients (n = 1051)	12.1%	< 40 yr, males	↓ HTN	Not difference in ALT and AST	↓ WC
Kawanaka et al[57], 2023	Compared lean with non-lean NAFLD patients (n = 782)	11%	> 50 yr, no difference between sexes	↓ HTN	↓ AST, ALT, TG, HOMA-IR, HbA1C	Not reported
Ishido et al[61], 2023	Compared lean with non-lean NAFLD patients (n = 581)	Not reported	Males, no difference between age	↓ HTN, T2DM	↓ AST, ALT, TG; ↑ HDL	↓ BMI

NAFLD: Non-alcoholic liver disease; T2DM: Type 2 diabetes mellitus; IR: Insulin resistance; HTN: Hypertension; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; MetS: Metabolic syndrome; HOMA-IR: Homoeostatic model assessment of insulin resistance; HDL: High density lipoprotein; WC: Waist circumference; WHR: Waist to hip ratio; BP: Blood pressure; LDL: Low density lipoprotein; FBG: Fasting blood glucose; BMI: Body mass index; AD: Atherogenic dyslipidemia; TG: Triglyceride; CVD: Cardiovascular disease; CKD: Chronic kidney disease; HbA1C: Hemoglobin A1C.

Table 2 Non-invasive scores accuracy and histology characteristics in lean patients with non-alcoholic fatty liver disease

Ref.	Population	Results
Leung et al[73], 2017	Histology (n = 307), lean vs obese NAFLD patients	Low NAS (steatosis and hepatocyte ballooning), low stiffness
Denkmayr et al[76], 2018	Histology (n = 466), lean vs overweight/obese NAFLD patients	High lobular inflammation and hepatocellular ballooning
Li et al[82], 2019	Scores (n = 898), lean vs overweight/obese NAFLD patients	WHR and FLI accurate in lean and obese patients, ZJU and HSI accurate in lean patients
Kim et al[75], 2019	Histology (n = 542), lean vs obese NAFLD patients	Low grade steatosis and NAS, high stage of fibrosis
Fu et al[81], 2020	Scores (n = 709), non-obese vs obese NAFLD patients	FIB-4, NFS, APRI, BARD score and AST-to-ALT ratio had similar accurate in obese and non-obese patients
Eren et al[79], 2022	Scores (n = 560), lean vs overweight vs severely and morbid obese NAFLD patients	FIB-4 and NFS cannot discriminate advance fibrosis in lean patients
Park et al[80], 2023	Scores (n = 1501), lean vs non-lean NAFLD patients	FIB-4 and NFS accurate in identify advance fibrosis in lean and non-lean NAFLD patients
Iwaki et al[74], 2022	Histology (n = 223), lean vs obese NAFLD patients	Low grade lobular inflammation, steatosis
Rastogi et al[77], 2022	Histology (n = 1273), lean vs overweight/obese NAFLD patients	High hepatocyte ballooning, early-stage fibrosis

NAFLD: Non-alcoholic liver disease; NAS: NAFLD activity score; WHR: Waist circumference; FLI: Fatty liver index; ZJU: Zhejiang University Index; HSI: Hepatic steatosis index; FIB-4: Fibrosis-4 index; NFS: NAFLD fibrosis score; APRI: AST-to-platelet; BARD: Bilirubin, albumin, INR and ascites; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.