Characteristics of non‐alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign

Abstract

Background and Aim To elucidate features of nonobese non‐alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex. Methods Biopsy‐proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI < 25 kg/m2), obese group (25 to 30), and severely obese group (≥ 30). Clinicopathological features and single nucleotide polymorphism of patatin‐like phospholipase 3 (PNPLA3) rs738409 were investigated, and body composition analysis was performed by bioelectrical impedance analysis and computed tomography. Results Over 25% of men and almost 40% of women were nonobese, but most of them had visceral fat obesity and/or insulin resistance. The median age (years) of the nonobese, obese, and severely obese men was 49.9, 46.8, and 40.5 (P < 0.01), respectively, while those of women was 60.2, 59.6, and 48.5 (P < 0.01), respectively. The prevalence of metabolic comorbidities and PNPLA3 risk alleles did not differ among these groups in both sexes. Also, the prevalence of non‐alcoholic steatohepatitis was not significantly different in both sexes, although nonobese patients had a higher prevalence of mild steatosis. Advanced fibrosis showed a marked difference between men and women. Advanced fibrosis was significantly more frequent among severely obese men (nonobese: 31.0%, obese: 41.6%, severely obese: 60.9%; P < 0.01), but it was lower among severely obese women (51.4%, 62.9%, 33.7%; P < 0.01). Skeletal muscle mass was significantly lower in nonobese patients. Conclusions Non‐alcoholic fatty liver disease was not milder in nonobese patients. Histological steatosis was associated with BMI, but advanced fibrosis was not and showed a significant sex difference.

Non‐alcoholic fatty liver disease in Asia: How is it different from the West?

“…In this large Japanese cohort of biopsy‐proven NASH patients, more than 25% male and around 40% female NASH patients were non‐obese. In contrast, most of them had visceral fat obesity and/or insulin resistance . More importantly, histological features were not milder in non‐obese NAFLD patients than their obese counterparts .…”

“…18 More importantly, histological features were not milder in non-obese NAFLD patients than their obese counterparts. 18 This leads to the concept of "metabolically obese," which refers to subjects with body mass index within the normal range, yet they have various metabolic risk factors. 19 This study adds fuel to the heated debate: Is lean NAFLD a more benign form of the disease comparing with the obese NAFLD?…”

“…In contrast, most of them had visceral fat obesity and/or insulin resistance . More importantly, histological features were not milder in non‐obese NAFLD patients than their obese counterparts . This leads to the concept of “metabolically obese,” which refers to subjects with body mass index within the normal range, yet they have various metabolic risk factors .…”

“…The different observations in the above studies may be partly explained by selection bias. The threshold to perform liver biopsy examination may be different in obese and non‐obese NAFLD patients in some centers—non‐obese group was older than the obese group (49.9 vs 40.5 years; P < 0.01) . A systematic review with meta‐analysis using patient‐level data would be helpful to evaluate with lean NAFLD patients really have worse outcomes.…”

“…The threshold to perform liver biopsy examination may be different in obese and non-obese NAFLD patients in some centers-non-obese group was older than the obese group (49.9 vs 40.5 years; P < 0.01). 18 A systematic review with meta-analysis using patient-level data would be helpful to evaluate with lean NAFLD patients really have worse outcomes. In any case, healthcare practitioners should not just focus on diagnosing NAFLD and the subsequent liver fibrosis assessment in obese subjects.…”