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NAFLD in lean individuals: not a benign disease
  1. Sven Francque1,2,
  2. Vincent Wai-Sun Wong3,4
  1. 1 Gastroenterology Hepatology, University Hospital Antwerp, Edegem, Antwerp, Belgium
  2. 2 Translational Research in Inflammation and Immunology (TW12N), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
  3. 3 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
  4. 4 State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  1. Correspondence to Dr Vincent Wai-Sun Wong, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong; wongv{at}; Prof Dr Sven Francque, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium; sven.francque{at}

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Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, affecting at least a quarter of the global adult population. It is rapidly becoming one of the most common indications for liver transplantation in Western countries. NAFLD is widely considered as the hepatic manifestation of the metabolic syndrome. It is particularly common among patients with type 2 diabetes and obesity. Nonetheless, emerging data suggest that NAFLD is present in a significant proportion of lean individuals. In a systematic review and meta-analysis of 93 studies (involving over 10 million individuals), Ye et al found that 19.2% and 40.8% of patients with NAFLD were lean and non-obese, respectively, according to ethnic-specific body mass index (BMI) cut-offs.1 However, over 80% of the studies included in this systematic review were from Asia, raising the suspicion that NAFLD in lean individuals is a unique phenomenon among Asians, especially as Asians are known to have more central fat deposition and develop NAFLD and metabolic complications at a lower BMI.2

In Gut, Younes et al now report a multicentre study on the clinical features, histological severity and clinical outcomes of 1339 Caucasian patients with biopsy-proven NAFLD from Italy, UK, Spain and Australia.3 Patients were grouped in lean and non-lean according to BMI<or ≥ 25 kg/m2. The first finding was the marked difference across the participating centres. Among the patients with NAFLD, 12.6%–41.7% of those from Italy were lean, compared with 13.5% in Australia, 3.2% in Spain, and 1.6% in the UK. While this may in part reflect a difference in patient selection for liver biopsy at the participating centres, there is likely considerable variability in the epidemiology of NAFLD in the lean population.

If a patient develops NAFLD despite being lean, this may represent the milder end of the …

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  • Contributors SMF and VW-SW contributed equally to the literature review and preparation of this commentary.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SMF served as consultant or advisory board member for Roche, Gilead Sciences, Allergan, Abbvie, Bayer, Bristol-Meyers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen Pharmaceutica, Actelion, Astellas, Genfit, Inventiva, Intercept, Echosens, Genentech, Novo Nordisk, Novartis, Astra Zeneca, Galmed, Promethera, Coherus, Madrigal, Julius Clinical and NGM Bio. He acted as speaker for Gilead Sciences, Genfit, Bayer, Abbvie, Intercept and Allergan. He received grants from Gilead, Roche, Bristol-Meyers Squibb and Genfit. Vincent Wong served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Center for Outcomes Research in Liver Diseases, Echosens, Gilead Sciences, Hanmi Pharmaceutical, Intercept, Inventiva, Merck, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions and Terns; and a speaker for AbbVie, Bristol-Myers Squibb, Echosens, and Gilead Sciences. He has received a grant from Gilead Sciences for fatty liver research.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; internally peer reviewed.

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