EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

Abstract

DefinitionNAFLD is characterised by excessive hepatic fat accumulation, associated with insulin resistance (IR), and defined by the presence of steatosis in >5% of hepatocytes according to histological analysis or by the proton density fat fraction (PDFF, providing a rough estimation of the volume fraction of fatty material in the liver) >5.6% assessed by proton magnetic resonance spectroscopy ( 1 H-MRS) or quantitative fat/water selective magnetic resonance imaging (MRI). NAFLD includes two pathologically distinct conditions with different prognoses: nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); the latter covers a wide spectrum of disease severity, including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) ( table 2 ).The diagnosis of NAFLD requires exclusion of both secondary causes and a daily alcohol consumption ≥ 30 g for men and 20 g for women [1] . The relationship between alcohol and liver injury depends on several cofactors (type of alcoholic beverage, drinking patterns, duration of exposure, individual/genetic susceptibility), rendering simple quantitative thresholds at least partly arbitrary. Specifically, patients consuming moderate amounts of alcohol may be still predisposed to NAFLD if they have metabolic risk factors. Of note, the overall impact of metabolic risk factors on the occurrence of steatosis appears to be higher than that of alcohol in these patients [3] . The definitive diagnosis of NASH requires a liver biopsy. Recommendations• Patients with IR and/or metabolic risk factors (i.e., obesity or metabolic syndrome (MetS)) should undergo diagnostic procedures for the diagnosis of NAFLD, which relies on the demonstration of excessive liver fat (A1) • Individuals with steatosis should be screened for secondary causes of NAFLD, including a careful assessment of alcohol intake. The interaction between moderate amounts of alcohol and metabolic factors in fatty liver should always be considered (A1) • Other chronic liver diseases, that may coexist with NAFLD, should be identified as this might result in more severe liver injury (B1) Prevalence and IncidenceNAFLD is the most common liver disorder in Western countries, affecting 17-46% of adults, with differences according to the diagnostic method, age, sex and ethnicity [4] . It parallels the prevalence of MetS and its components, which also increases the risk of more advanced disease, both in adults and in children. NAFLD is also present in 7% of normalweight (lean) persons [5] , more frequently in females, at a younger age and with normal liver enzymes. Their liver disease may nonetheless be progressive [6] .NAFLD incidence has rarely been measured. It was 20-86/1,000 person-years based on elevated liver enzymes and/or on ultrasound (US), and 34/1,000 per year by 1 H-MRS [7] . The need for NAFLD screening in the community has been questioned given the high direct and indirect costs of testing, the low predictive value of non-invasive tests, the risks of liver biopsy and the lack of effective treatments [8] . Ho...

Metabolomic‐based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts

“…They found that the AUROC of these biomarkers ranged from 0.80 to 0.88 35. Some of these biomarkers have been suggested by the recent European Association for the Study of the Liver guidelines to assess the severity of fibrosis and rule out advanced stages 23. However, there were no recommendations on any biomarkers to diagnose NASH; liver biopsy remained the only recommendation for this in the recent guidelines.…”

“…Biopsies that showed total disagreement among the three pathologists were excluded from the analysis. The histopathologic definition of NASH was determined by the joint presence of steatosis, lobular inflammation, and hepatocellular ballooning on liver specimens, independently of the total NAFLD activity score (NAS) 23. Biopsies with only steatosis, steatosis with inflammation but without ballooning, or steatosis with ballooning but without inflammation were classified as NAFL.…”

Diagnosis of non-alcoholic fatty liver disease (NAFLD)

“…The European Associations for the Study of the Liver (EASL), Diabetes (EASD) and Obesity (EASO) have recently worked together on Clinical Practice Guidelines for the management of NAFLD [7]. According to these guidelines, all individuals with incidentally discovered steatosis should be screened for features of the metabolic syndrome, independently of liver function tests (LFTs).…”

“…1), and the screening includes assessment of dietary and lifestyle habits. As regards diet, in addition to total energy intake, particular emphasis should be paid to consumption of simple sugars and saturated fats, both of which are important risk factors for obesity and, independently of obesity for type 2 diabetes, CVD and NAFLD [7,37]. In addition, LFTs, platelets and albumin should be measured to enable calculation of a non-invasive score for NAFLD, such as the NAFLD fibrosis score (based on age, BMI, impaired fasting glucose/diabetes, AST, ALT, platelets, albumin; calculator found at www.…”

“…TE is sensitive and specific in excluding advanced stage 3-4 fibrosis but fails in approximately 20%, mainly due to obesity [38]. Diagnosis of NASH still requires a liver biopsy [7]. In patients with steatosis who initially have normal liver enzymes and low fibrosis biomarkers, these measurements should be repeated every 2 years.…”