Lean nonalcoholic fatty liver disease: Age-dependent differences in pathology, prognosis, and liver-related events

This study aimed to evaluate the age-specific characteristics, prognosis, and complications of patients with lean nonalcoholic fatty liver disease (NAFLD).

Background factors (age, sex, diabetes, dyslipidemia, hypertension, and PNPLA3 gene polymorphism), blood test results, liver histology findings, muscle mass, and grip strength were investigated in 782 patients with NAFLD who underwent liver biopsy. Prognosis and complications were compared among 549 patients with nonlean or lean NAFLD who were followed up for 6.5 years. Additionally, background factors, blood test results, liver histology findings, prognosis, and complications were compared according to age (≥60 years vs. <60 years) in patients with lean NAFLD.

Lean NAFLD patients showed lower aspartate aminotransferase, alanine aminotransferase, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein, ferritin, and leptin but higher adiponectin and hemoglobin A1c (HbA1c) levels than patients with nonlean NAFLD. Furthermore, lean NAFLD patients showed less liver fibrosis, inflammation, steatosis, and ballooning. Among lean NAFLD patients, those aged 60 years and older were more frequently female, showed higher rates of hypertension, diabetes, and dyslipidemia, had higher HbA1c and type IV collagen 7S levels, lower platelet count, higher liver fibrosis and inflammation grades, and lower muscle mass and grip strength. Lean NAFLD was associated with a worse prognosis in patients aged 60 years and over than in those younger than 60 years of age and with a higher incidence of liver-related disease, cerebrocardiovascular events, and nonliver cancer.

Age is an important consideration in patients with lean NAFLD. Compared with nonlean NAFLD, lean NAFLD was associated with a worse prognosis and higher risk of complications in patients aged 60 years and older.