From NAFLD to MASLD: What's in a Name?

Kevin Fernando, MBChB, MSc


October 11, 2023

Until recently, my practice of managing nonalcoholic fatty liver disease (NAFLD) has been to offer some cursory advice on weight management and file the result as completed in the patient's notes. However, I am becoming increasingly aware of the gravity of a diagnosis of NAFLD, and of the need to identify individuals at high risk and intervene appropriately to prevent the debilitating consequences. This new awareness was heightened in several sessions at the European Association for the Study of Diabetes (EASD) 2023 Annual Meeting in Hamburg, Germany, which I was fortunate enough to attend.

Kevin Fernando, MBChB, MSc

NAFLD is commonly encountered in primary care; it is often found incidentally when arranging an ultrasound scan for another reason, such as possible gallbladder disease. During 2019, it was estimated that 38% of adults and approximately 10% of children and adolescents worldwide had NAFLD. Moreover, NAFLD is highly prevalent in patients with type 2 diabetes (T2D); the global prevalence of NAFLD in T2D is 67%.

In Western countries, NAFLD (specifically the progressive inflammatory stage of nonalcoholic steatohepatitis, or NASH) is now the most common liver disorder and the fastest-growing indication for liver transplantation.

NAFLD has been renamed by recent international consensus to increase awareness of the condition and improve patient identification. Equally important is that the renaming is intended to reduce the stigma associated with the diagnosis. The new name reflects the heterogeneous nature of NAFLD, as it was a diagnosis of exclusion: steatosis in the absence of alcohol consumption above a certain threshold, and without other known secondary causes of steatosis, including iatrogenic causes like amiodarone, tamoxifen, and methotrexate.

NAFLD is now called metabolic dysfunction–associated steatotic liver disease (MASLD). MASLD encompasses individuals who have hepatic steatosis and at least one of these five cardiometabolic risk factors:

  • BMI ≥ 25 (23 in Asia) or waist circumference > 94 cm for men or > 80 cm for women, or ethnically adjusted

  • Fasting serum glucose ≥ 5.6 mmol/L (100 mg/dL) or 2-hour post-load glucose levels ≥ 7.8 mmol/L (≥ 140 mg/dL) or A1c ≥ 5.7% (39 mmol/mol) or T2D or treatment for T2D

  • Blood pressure ≥ 130/85 mm Hg or specific antihypertensive drug treatment

  • Plasma triglycerides ≥ 1.70 mmol/L (150 mg/dL) or lipid-lowering treatment

  • Plasma HDL cholesterol ≤ 1.0 mmol/L (40 mg/dL) in men and ≤ 1.3 mmol/L (50 mg/dL) in women, or lipid-lowering treatment

In essence, MASLD is primarily a metabolic disease that is heavily influenced by lifestyle factors. It is the liver's manifestation of the metabolic syndrome (MetS).

Furthermore, there is a bidirectional relationship between MASLD and T2D; MASLD itself is associated with a 2.2-fold increased risk of developing T2D that is partly driven by increased hepatic glucose production and insulin resistance. This risk has significant implications for clinical practice regarding screening for these conditions.

We should consider screening all patients with steatosis (incidentally found or otherwise) for features of MetS, independent of liver blood tests. Conversely, we should consider screening for MASLD in patients with obesity or MetS.

Metabolic dysfunction–associated steatohepatitis (MASH) replaces NASH. This new name maintains the concept of steatohepatitis as a separate entity and does not change the current definition based on histology. Unfortunately, there is a high prevalence of MASH and advanced fibrosis in patients with T2D and MASLD. The global prevalence of MASH among patients with T2D is approaching 40%. MASH carries an increased risk for progression to advanced fibrosis, hepatocellular carcinoma (HCC), and other adverse liver-related outcomes.

MetALD describes individuals with MASLD who consume more than the recommended amounts of alcohol per week (around 17.5 units/wk for women and 26 units/wk for men). The study of patients with MetALD remains an unmet investigational need.

This new nomenclature will allow better characterization of all factors contributing to steatotic liver disease and its severity. It will facilitate the appropriate management of all underlying causes. It will also inform the design of future studies.

Society guidelines are changing across the world to advocate screening for advanced fibrosis in patients with T2D.

Joint EASL-EASD-EASO guidance was published during 2016 and advocated screening for NAFLD in patients with T2D, irrespective of liver enzyme levels, because these individuals are at high risk for disease progression. This older guidance, however, gives no specific recommendation on which biomarkers or scores of fibrosis to use in this context.

In contrast, the recently updated American Diabetes Association Standards of Care in Diabetes–2023 guidance specifically recommends risk stratification for advanced fibrosis using the noninvasive Fibrosis-4 (FIB-4) scoring system. FIB-4 is calculated by the laboratory using age, AST, ALT, and platelets. It also stages disease severity. FIB-4 was determined to be the most cost-effective strategy for the initial screening of patients with prediabetes and cardiometabolic risk factors or T2D.

If the FIB-4 score is indeterminate or high, second-line, noninvasive testing such as transient elastography techniques (eg, FibroScan) or the enhanced liver fibrosis blood test is recommended. If second-line testing suggests low risk for advanced fibrosis, then risk stratification can be repeated in 2-3 years. If a patient has high risk for advanced fibrosis, then referral to hepatology is recommended.

Regarding the management of MASLD, we need to strongly encourage and facilitate weight loss where possible. Weight loss of 3%-5% reduces hepatic steatosis; loss of 5%-7% or more can lead to resolution of MASH, and loss of 10% or more improves hepatic fibrosis.

Additionally, active management of any coexisting features of MetS and, ideally, abstinence from alcohol consumption, are required. Cardiovascular risk should be assessed with consideration of lipid-lowering therapy, including for patients with abnormal baseline liver blood tests. Statins can be initiated if liver blood tests are less than three times the upper limit of normal. Of note, emerging evidence suggests that statin use is associated with a reduction in liver cancer risk.

There is also evidence brewing that coffee promotes liver health and decreases the risk for fibrosis, cirrhosis, and HCC in chronic liver disease, including MASLD. No specific recommendations have been made about quantity of coffee consumption, but a moderate intake of three to five cups per day may be beneficial.

Finally, there are no current licensed drug therapies for MASLD or MASH. Compelling evidence, however, is emerging for pioglitazone; SGLT2 inhibitors; GLP-1 receptor agonists; the dual GLP-1 and GIP receptor agonist tirzepatide; and the triple GLP-1, GIP, and glucagon agonist ("triple-G") retatrutide.

The renaming of NAFLD to MASLD reflects a paradigm shift in how we understand and manage this condition. It will no doubt have significant workload implications for healthcare professionals in primary care, in regard to screening and addressing metabolic risk factors. As MASLD is mostly a silent disease until later stages, however, it is important to identify individuals at high risk for advanced liver fibrosis and intervene appropriately to prevent the debilitating consequences of advanced liver disease, which can include cirrhosis, HCC, and an increased risk for mortality.

Dr Fernando is a general practitioner near Edinburgh, Scotland, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

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