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2021 REVERSING FATTY LIVER DISEASE WITH HEALTHY LIFESTYLE 1 Authors: Massimiliano Ruscica, Paola Dongiovanni, Leen Heyens, Geert Robaeys Affiliations of the authors: 1 Massimiliano Ruscica Paola Dongiovanni2 Leen Heyens3-5 Geert Robaeys3,5,6 1 Università degli studi di Milano, Department of Pharmacological and Biomolecular Sciences, Milan, Italy 2 General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy 3 Hasselt University, Faculty of Health and Life Sciences, Diepenbeek, Belgium 4 Maastricht University, School of Nutrition and Translational Research in Metabolism, NUTRIM, Maastricht, the Netherlands 5 Ziekenhuis Oost-Limburg, Department of Gastro-enterology and Hepatology, Genk, Belgium 6 University Hospital KU Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium Editor: Stephanie De Vriese7 7 Secretary of Alpro Foundation This review is fully supported by the Scientific Advisory Committee of the Alpro Foundation: Harry Aiking (VU University Amsterdam); Anna Arnoldi (University Milano); Peter Clarys (Vrije Universiteit Brussel); Christine Debeuf (Alpro); Stephanie De Vriese (Alpro); Helmut Heseker (University Paderborn); Sander Kersten (University Wageningen); Ian Rowland (University Reading); Cesare Sirtori (University Milano); and Kurt Widhalm (University Vienna) Date: June 2021 CONTENT Introduction .............................................................................................................................................................................. 4 Genetic and environmental factors associated with NAFLD ......................................................................................... 6 Primary therapeutic advice: lifestyle changes emphasizing weight reduction........................................................ 7 Mediterranean diet ............................................................................................................................................................................... 9 Role of plant protein .......................................................................................................................................................................... 10 The role of gut microbiome ..............................................................................................................................................................11 Other treatment options .....................................................................................................................................................................11 NAFLD and childhood ........................................................................................................................................................... 12 Conclusion ............................................................................................................................................................................... 12 References ............................................................................................................................................................................... 13 INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is people with type 2 diabetes (T2DM) and up to 80% considered the most frequent cause of liver of people with obesity. However, some people disorders with a prevalence above 30% in many with a healthy body mass index (BMI) can still adult populations.1,2 The highest prevalence is develop NAFLD, often described as non-obese or reported in the Middle East (32%) and South lean NAFLD. These patients usually have central America (31%), followed by Asia (27%), USA (24%) obesity or other metabolic risk factors.3 Patients and Europe (23%), with the lowest in Africa (14%). with NAFLD have 2.5 times higher incidence of Because of its close association with metabolic cardiovascular disease (CVD). syndrome (MetS), NAFLD is seen in 47.3–63.7% of FIGURE 1. THE NATURAL EVOLUTION OF NAFLD OR METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD). The mechanisms underlying NAFLD pathogenesis are multifactorial. Histologically, NAFLD encompasses a continuum including steatosis with or without mild inflammation (NAFL), NASH with/without fibrosis, cirrhosis, and hepatocellular carcinoma. Equally, environment, gut microbiota, genetics, and epigenetics influence the disease onset and progression. The first step in NAFLD development is hepatic fat infiltration, mainly due to IR. This leads to a rise in the adipose tissue lipolysis with the consequent efflux of free fatty acids to the liver. The compensatory hyperinsulinemia exacerbates fat accumulation. Excess fat is cleared from the liver by an enhanced lipoprotein secretion and mitochondrial β-oxidation. The latter results in increased reactive oxygen species production leading to the activation of inflammatory pathways. Abbreviations: IR, insulin resistance; MAFLD, metabolic associated fatty liver disease; NAFL, non-alcoholic fatty liver; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis. Adapted from: Dongiovanni P et al. 2021 and Heyens LJM et al. 2021. 68,69 4
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