Page 991 - Read Online

Page 12 of 18 Machado. Hepatoma Res 2020;6:84 I http://dx.doi.org/10.20517/2394-5079.2020.90

MANAGEMENT
The main treatment in MAFLD is lifestyle modification in order to lose weight targeting normal weight [167] .
Lean-NAFLD patients already have normal weight, should weight loss be pursued? What would be the
target weight loss?

Epidemiological studies taught us that even in the normal weight range, the lower the BMI, the lower
[20]
the risk for NAFLD [21,36] . Also, lean patients with NAFLD frequently present with VAT expansion . The
[52]
concept that everyone has their own personal fat threshold suggests that weight loss decreasing adiposity
below the fat threshold might be beneficial metabolically and to the liver. In fact, in a small study with 20
lean-NAFLD patients, any weight loss was associated with steatosis improvement, and being above 5%
corporal weight was associated with improvement in NAFLD activity score [168] .

Exercise should be highly encouraged. Exercise, particularly aerobic exercise, seems to preferentially target
VAT over SAT [169] . Also a significant decrease in VAT can occur even without significant weight loss [170] .
Patients should be advised to perform aerobic exercise below current recommendations for overweight/
obese, with at least 150 min per week of moderate intensity exercise (for example, brisk walking, light
jogging, or stationary ergometer usage) [171] .

Cardiometabolic risk factors should be aggressively treated. Of note, incretin-based therapy may be more
[47]
effective in overweight/obese because it associates with weight loss . On the contrary, thiazolidinediones
promote adipocyte differentiation and fat cell hyperplasia in adipocytes in subcutaneous compartments,
[58]
and may be more effective in MONW patients .

Lastly, modulation of gut microbiota in the treatment of lean-NAFLD should be further explored, giving
the known role of gut dysbiota in its pathogenesis.

CONCLUSION
Lean-NAFLD is a frequent condition in the daily practice of hepatologists. Efforts should be made to
differentiate between lean MAFLD and other conditions that are also associated with hepatic steatosis,
such as other liver diseases (for example, chronic viral hepatitis and Wilson’s disease), small bowel diseases
with malabsorption (for example, celiac disease and Crohn’s disease), and inborn errors of metabolism (for
example, LAL-deficiency).

Patients with lean MAFLD have a disorder of the adipose tissue, despite their normal weight. Each
individual might have his own personal fat threshold that when exceeded results in adipose tissue
malfunction, cardiometabolic disturbances, and ectopic fat accumulation in the liver. The personal
fat threshold is dependent on the different compartmentalization of the adipose tissue (visceral vs.
subcutaneous and upper vs. lower body fat) as well as intrinsic properties of the adipose tissue that allow it
to deal with fat challenges (hypertrophic vs. hyperplasic responses to energy surplus).

Patients with lean-NAFLD/MAFLD can have the whole spectrum of liver disease from isolated steatosis
to liver cirrhosis and end-stage liver disease. Although studies evaluating the prognosis of lean NAFLD/
MAFLD are scarce, lean patients probably do not have a more benign prognosis as overweight/obese
patients.

Management of patients with lean NAFLD/MAFLD should follow the same principles as for non-lean
patients. Lifestyle modifications should be advised in order to address visceral fat. Weight loss might be
beneficial even in patients with normal BMI, for whom their personal fat threshold falls below the upper
normal BMI cutoff.