You are here
European Associations published guidelines on NAFLD
Three European Associations have announced Clinical Practice Guidelines (CPG) for the management of non-alcoholic fatty liver disease (NAFLD), which state that “by improving obesity and diabetes, bariatric (metabolic) surgery reduces liver fat and is likely to reduce NASH progression; prospective data have shown an improvement in all histological lesions of NASH, including fibrosis.” The CPG, ‘EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease’, published in the Journal of Hepatology, are the product of a joint effort by the European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO).
The guidelines propose recommendations for the diagnosis, treatment and follow-up of NAFLD patients and are an update a position statement, ‘A position statement on NAFLD/NASH based on the EASL 2009 special conference’, based on the 2009 EASL Special Conference.
The CPG states that “NAFLD 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 (1H-MRS) or quantitative fat/water selective magnetic resonance imaging (MRI). NAFLD includes two pathologically distinct conditions with different prognoses: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); the latter covers a wide spectrum of disease severity, including fibrosis, cirrhosis and hepatocellular carcinoma (HCC).”
It recommends that:
- 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.
- 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
- Other chronic liver diseases, that may coexist with NAFLD, should be identified as this might result in more severe liver injury
The guidelines state that lifestyle and more specifically, diet, play a significant role in the development of NAFLD. In particular it states that a “high-calorie diet, excess (saturated) fats, refined carbohydrates, sugar-sweetened beverages, a high fructose intake and a Western diet have all been associated with weight gain and obesity, and more recently with NAFLD. High fructose consumption may increase the risk of NASH and advanced fibrosis, although the association may be confounded by excess calorie intake or by unhealthy lifestyles and sedentary behaviour, which are more common in NAFLD.”
With regards to obesity, it states that BMI and waist circumference are positively related to the presence of NAFLD and predict advanced disease, particularly in the elderly. In addition, a large proportion of patients with cryptogenic cirrhosis have a high prevalence of metabolic risk factors, this suggests that in the majority of cases of cryptogenic cirrhosis are ‘burned-out' NASH. Common comorbidities of obesity, such as T2DM, and sleep apnoea , polycystic ovary syndrome and other endocrine disorders (hypogonadism), further drive NAFLD prevalence and severity.
Importantly, patients with BMI 30 but with visceral fat accumulation or dysfunctional adipose tissue can exhibit NAFLD with/without abnormal liver enzymes.
“The currently used concept of ‘metabolically healthy' obese individuals should be considered with caution, given that they may exhibit gene expression similar to those of metabolically altered obese patients, and may have altered liver tests and adverse health outcomes when longitudinally examined.”
Therefore, the recommendations state that:
- Obesity is the major phenotype and risk condition for NAFLD, driven by IR, which also increases the risk of advanced disease
- Most lean persons with NAFLD display IR and altered body fat distribution even though they have less severe metabolic disturbance than overweight NAFLD. Follow-up is nonetheless required because of possible disease progression
With regards to T2DM, it reports that patients are insulin resistant, often obese, dyslipidaemic, display increased liver enzymes and tend to accumulate hepatic fat independently of BMI. The prevalence of NAFLD is also higher in persons at risk of T2DM, defined as a glycosylated haemoglobin A1c (HbA1c) of 5.7-6.4% (38.8-46.4mmol/mol), IFG (fasting glucose: 100-125mg/dl (5.55-6.94mmol/l)) and/or impaired glucose tolerance (IGT; glucose: 140-199 mg/dl (7.77-11.04mmol/l) at two hours of the standardised 75g oral glucose tolerance test (OGTT)).
Diabetes risk and T2DM closely associate with the severity of NAFLD, progression to NASH, advanced fibrosis and the development of HCC, independently of liver enzymes. Conversely, US-defined NAFLD is associated with a two- to five-fold risk of developing T2DM after adjustment for several lifestyle and metabolic confounders. The standardised 75g OGTT should therefore be performed in persons with increased diabetes risk.
Insulin treatment increases body fat, but it does not appear to promote or worsen NAFLD in diabetes, while acute insulin infusion dose-dependently increases liver fat content in T2DM, chronic insulin treatment improves adipose tissue IR and therefore reduces NEFA flux and hepatic fat content.
The CPG recommends that:
- In persons with NAFLD, screening for diabetes is mandatory, by fasting or random blood glucose or HbA1c and, if available, by the standardised 75g OGTT in high-risk groups
- In patients with T2DM, the presence of NAFLD should be looked for irrespective of liver enzyme levels, since T2DM patients are at high risk of disease progression
The CPG states that patients who are unresponsive to lifestyle changes and pharmacotherapy, bariatric surgery is an option for reducing weight and metabolic complications, with stable results in the long term. Research has shown that surrogate markers indicate that bariatric surgery is effective on NAFLD-associated liver injury, and there is also initial evidence for improved necro-inflammation and fibrosis. A recent cohort study, Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States’, with one-year follow-up confirmed that bariatric surgery-associated weight loss cleared NASH in 85% of patients and improved fibrosis in 34%, although the possible benefits should be balanced against peri-/post-operative complications. However, the CPG state that no solid data on the comparative effects of different bariatric procedures on liver fat are available.
The article was edited from the original article, under the Creative Commons license.
To access this article, please click here