Diet and non-alcoholic fatty liver disease, a short narrative review.

The growing importance of non-alcoholic fatty liver disease (NAFLD), the biggest non-communicable liver disease, inherently leads to an increased attention to lifestyle and diet that are closely intertwined with NAFLD. Elements of the Western diet such as saturated fats and carbohydrates and thus soft drinks, red meat and ultra-processed foods are linked to NAFLD. Contrarily, diets rich in nuts, fruits, vegetables and unsaturated fats as seen in the Mediterranean diet are linked to less prevalent and less severe NAFLD. In the absence of approved medical therapy for NAFLD, therapy mostly focusses on lifestyle and diet. This short review tries to provide a succinct overview of the current knowledge on the influence of certain diets or individual nutrients on NAFLD and discusses different dietary approaches. It ends with a short list of recommendations that can be used in daily practice.

Sarcopenia in patients with non-alcoholic fatty liver disease: is it a clinically significant entity?

Sarcopenia, described as the loss of muscle mass and/or strength, is gaining importance as it can be increasingly related to many chronic diseases. It is also associated with chronic liver disease, and recently it has been more frequently linked to non-alcoholic fatty liver disease (NAFLD) in particular. Both sarcopenia and NAFLD are subject to complex and intermingled pathophysiological processes, of which some are in common. Furthermore, it is presently unclear if sarcopenia directly contributes to NAFLD or vice versa. The mechanisms that are involved may include obesity, insulin resistance, vitamin D deficiency, aging, physical inactivity and certain cytokines. Current clinical evidence is subject to an important heterogeneity in methods and definitions, with additionally also a relative overrepresentation of evidence in Asian ethnicities. Nonetheless, all studies so far point towards the same association between sarcopenia and NAFLD, including an association with NAFLD-severity and NAFLD-related fibrosis. Since the field is in its infancy, clear definitions and further research are needed to aid to improve understanding of the association between NAFLD and sarcopenia. This can eventually lead to additional potential therapeutic interventions. This review attempts to give an overview of the current published literature that links sarcopenia to NAFLD, followed by a discussion of the presumably involved pathophysiological factors, and ends by discussing current unmet needs.

The potential role of vascular alterations and subsequent impaired liver blood flow and hepatic hypoxia in the pathophysiology of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from steatosis to steatohepatitis (NASH) and fibrosis, but the underlying pathophysiological mechanisms remain largely unknown. As there is currently no approved pharmacological therapy and the prevalence of NAFLD keeps increasing, understanding of its pathophysiology is crucial. We hypothesise that vascular alterations in early NAFLD play a role in the progression of the disease by inducing an increased intrahepatic vascular resistance and consequently relative hypoxia in the liver. Evidence of the detrimental effects of hypoxia in NAFLD has already been observed in liver surgery, where the outcomes of steatotic livers after ischaemia-reperfusion are worse than in healthy livers, and in obstructive sleep apnoea, which is an independent risk factor of NAFLD. Moreover, early histological damage in NAFLD is situated in the pericentral zone, which is also the first zone to be affected by a decreased oxygen tension because of the unique hepatic vacsular anatomy that causes the pericentral oxygen tension to be the lowest. Angiogenesis is also a characteristic of NAFLD, driven by hypoxia-induced mechanisms, as demonstrated in both animal models and in humans with NAFLD. Relative hypoxia is most probably induced by impaired blood flow to the liver, caused by increased intrahepatic vascular resistance. An increased intrahepatic vascular resistance early in the development of disease has been convincingly demonstrated in several animal models of NAFLD, whereas an increased portal pressure, a consequence of increased intrahepatic vascular resistance, has been proven in patients with NAFLD. Animal studies demonstrated a decreased intrahepatic effect of vasodilators and an increased reactivity to vasoconstrictors that results in an increased intrahepatic vascular resistance, thus the presence of a functional component. Pharmacological products that target vasoregulation can hence improve the intrahepatic vascular resistance and this might prevent or reverse progression of NAFLD, representing an important therapeutic option to study. Some of the drugs currently under evaluation in clinical trials for NASH have interesting properties related to the hepatic vasculature. Some other interesting drugs have been tested in animal models but further study in patients with NAFLD is warranted. In summary, in this paper we summarise the evidence that leads to the hypothesis that an increased intrahepatic vascular resistance and subsequent parenchymal hypoxia in early NAFLD is an important pathophysiological driving mechanism for the progression of the disease.

The Belgian Association for Study of the Liver Guidance Document on the Management of Adult and Paediatric Non-Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and associated with considerable liver-related and non-liverrelated morbidity and mortality. There is, however, a lot of uncertainty on how to handle NAFLD in clinical practice. The current guidance document, compiled under the aegis of the Belgian Association for the Study of the Liver by a panel of experts in NAFLD, from a broad range of different specialties, covers many questions encountered in daily clinical practice regarding diagnosis, screening, therapy and follow-up in adult and paediatric patients. Guidance statements in this document are based on the available evidence whenever possible. In case of absence of evidence or inconsistency of the data, guidance statements were formulated based on consensus of the expert panel. This guidance document is intended as a help for clinicians (general practitioners and all involved specialties) to implement the most recent evidence and insights in the field of NAFLD within a Belgian perspective.