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©The Author(s) 2020.
World J Gastroenterol. Nov 14, 2020; 26(42): 6514-6528
Published online Nov 14, 2020. doi: 10.3748/wjg.v26.i42.6514
Published online Nov 14, 2020. doi: 10.3748/wjg.v26.i42.6514
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 |
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 |
Table 3 Key elements of management of lean non-alcoholic fatty liver disease
| Evaluation of severity of liver | Liver fibrosis (serological markers, elastography, biopsy) |
| Presence of NASH (biopsy or serological evidence of inflammation) | |
| Weight reduction | 5% of body weight reduction can be effective in reducing steatosis |
| Physical activity | Positive effect regardless of weight reduction |
| Dietary Intervention | ↓ Fat intake, ↑ protein intake |
| Commorbidities | Strict control of: |
| Diabetes mellitus (consider pioglitazone) | |
| Hypertriglyceridemia (baseline triglyceride count was independently correlated with NAFLD resolution) | |
| Hypercholesterolemia (reduction of total cholesterol was independently correlated with steatosis reduction) | |
| Hypertension | |
| Sleep patterns | Emphasize the significance of adequate sleep duration and quality |
| Pharmacological therapy | Pioglitazone and vitamin E as the only accepted therapies, but proposed only on an individual basis |
| Possible role of probiotics | |
| Small number of trials for lean patients | |
| According to the results of trials focusing on non-lean patients |
- Citation: Chrysavgis L, Ztriva E, Protopapas A, Tziomalos K, Cholongitas E. Nonalcoholic fatty liver disease in lean subjects: Prognosis, outcomes and management. World J Gastroenterol 2020; 26(42): 6514-6528
- URL: https://www.wjgnet.com/1007-9327/full/v26/i42/6514.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i42.6514