![]() In contrast, triglyceride accumulation appears to be an adaptive mechanism minimising hepatocyte injury from lipotoxicity caused by reactive lipids and fatty acids, such as cholesterol, FFAs, oxysterols or phospholipids. Traditionally, steatosis severity is graded according to the extent of triglyceride accumulation despite the recognition that, in general, triglycerides per se do not cause hepatocyte injury. Main sources of hepatic lipid aggregation are a flux of free fatty acids (FFA) from peripheral adipose tissue (59%), followed by hepatic de novo lipogenesis (26%) and dietary intake (14%) ( 4). Hepatocellular fat accumulation arises when lipid export or degradation is exceeded by lipid import or synthesis. The heterogeneity of disease progression is reflected in the multi-faceted pathogenesis of NAFLD. Mirroring the obesity pandemic, its clinical and economic burden is reaching enormous proportions: 52 million people are estimated to suffer from NAFLD in Germany, France, Italy and the UK, incurring annual direct medical costs of €35 billion ( 2, 3). Its mounting prevalence and potentially aggressive nature combined with diagnostic and therapeutic barriers make NAFLD an important public health concern of the 21st century ( 3). In its advanced stages, NAFLD may progress to cirrhosis and its complications, including HCC. This heterogeneous continuum ranges from simple, isolated steatosis (non-alcoholic fatty liver (NAFL)) to steatohepatitis with evidence of hepatocyte injury and necroinflammation (non-alcoholic steatohepatitis (NASH)) with or without hepatic fibrosis. Regarded as the hepatic manifestation of the metabolic syndrome in view of its intimate association with insulin resistance, obesity, hypertension and dyslipidaemia, NAFLD is a multi-system disease encompassing a histopathological spectrum of severity. NAFLD is defined as the accumulation of liver fat (exceeding 5% of hepatocytes) without evidence for coexisting hepatic insults, namely viral or autoimmune hepatitis, use of steatogenic medication, or significant alcohol intake ( 2). Non-alcoholic fatty liver disease (NAFLD) is recognised as the most common aetiology of chronic liver disease, with an estimated global prevalence of 25.2%, and as a major cause of cirrhosis and hepatocellular carcinoma (HCC), projected to become the leading indication for liver transplantation during this decade ( 1). This review summarises the current concepts in diagnosis and disease progression of non-alcoholic liver disease, focusing on pragmatic approaches to risk assessment and management in both primary and secondary care settings. Despite the current lack of licensed, liver-targeted pharmacotherapy, several promising agents are undergoing late-phase clinical trials to complement standard management in patients with advanced disease. A multidisciplinary approach to treatment is advised, centred on amelioration of cardiometabolic risk through lifestyle and pharmacological interventions. This necessitates risk stratification of patients by fibrosis stage using combinations of non-invasive methods, such as composite scoring systems and/or transient elastography. The presence and severity of fibrosis are the most important prognostic factors in non-alcoholic fatty liver disease. Patients with non-alcoholic fatty liver disease show variable rates of disease progression through a histological spectrum ranging from steatosis to steatohepatitis with or without fibrosis. Its high clinical burden results from the growing prevalence, inherent cardiometabolic risk and potential of progressing to cirrhosis. It does not store any personal data.Non-alcoholic fatty liver disease is a chronic liver disease which is closely associated with components of the metabolic syndrome. The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. The cookie is used to store the user consent for the cookies in the category "Performance". This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other. ![]() The cookies is used to store the user consent for the cookies in the category "Necessary". The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional". The cookie is used to store the user consent for the cookies in the category "Analytics". These cookies ensure basic functionalities and security features of the website, anonymously. Necessary cookies are absolutely essential for the website to function properly. ![]()
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