Identification and Management of People with MASLD and MASH

• There has been recent international consensus to rename non-alcoholic fatty liver disease (NAFLD) to improve awareness and patient identification and reduce stigma^[1]
• NAFLD is now termed metabolic dysfunction-associated steatotic liver disease (MASLD)^[1]
  • MASLD encompasses individuals who have hepatic steatosis and at least one cardiometabolic risk factor^[2]
• Metabolic dysfunction-associated steatohepatitis (MASH) replaces non-alcoholic steatohepatitis (NASH).^[2] MASH is defined by inflammation of hepatocytes and carries a risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC)
• MetALD describes individuals with MASLD who consume more than recommended amounts of alcohol per week (around 17.5 units/week for women and 26 units/week for men)
• MASLD is primarily a metabolic disease heavily influenced by lifestyle factors, and is the liver’s manifestation of the metabolic syndrome (MetS) alongside hypertension, insulin resistance and dysglycaemia, dyslipidaemia, and obesity/increased waist circumference.^{[4] [5]}

• MASLD is now the most common liver disorder in Western countries, and has been estimated to affect up to 30% of adults in the UK^{[6] [7]}
  • MASH has been estimated to affect up to 5% of the UK population^[6]
• MASLD (specifically the progressive MASH) is the fastest growing indication for liver transplantation in Western countries^[8]
• MASLD is also associated with an increased prevalence and incidence of cardiovascular disease (CVD)^[9]
  • CVD is a more common cause of death than liver disease in MASLD^[9]
• MASLD is highly prevalent in people living with type 2 diabetes (T2D); the global prevalence of MASLD in T2D is 67%.

• The appearance of steatosis on abdominal ultrasound (USS) are operator-dependent and a normal USS does not rule out MASLD^[15]
• Consider screening all individuals with steatosis (e.g. incidentally found on USS) for features of MetS, independent of liver blood tests
• Consider screening for MASLD with liver blood tests and/or USS in people living with obesity or MetS
• In high-risk individuals (aged >50 years, T2D, MetS) active case finding for advanced disease (that is, MASH) is recommended (see below).

• Check body mass index, waist circumference and blood pressure^[16]
• Check bloods to exclude coexisting liver disease (if there are abnormal liver blood tests) and metabolic conditions depending on clinical judgement. Not everyone needs a full liver screen!^[16]
• See the NICE Clinical Knowledge Summary on NAFLD for further guidance on arranging blood tests, but consider the following in the first instance:^[16]
  • liver blood tests
  • lipid profile
  • glycated haemoglobin A_1c (HbA_1c); see the Primary Care Hack, Type 2 Diabetes Cardiovascular Renal Metabolic Review Checklist
  • hepatitis serology
  • full blood count
  • iron studies (see the Primary Care Hack on Interpreting Iron Studies in Primary Care
  • autoantibodies and immunoglobulins
• Assess the risk of advanced liver fibrosis using a non-invasive scoring system such as the Fibrosis-4 (FIB-4) score.^[16] FIB-4 is calculated by the laboratory using age, AST, ALT, and platelets, and stages disease severity^[17]
• The British Society of Gastroenterology (BSG) has produced an algorithm for the diagnosis of NAFLD and non-invasive assessment of liver fibrosis.^[18]

• Strongly encourage and facilitate weight loss where possible: weight loss 3–5% reduces hepatic steatosis, ≥5–7% can lead to resolution of MASH, and ≥10% improves hepatic fibrosis^[19]
• Aim for moderate-intensity exercise training for 150–200 minutes per week in 3–5 sessions where possible
• The EASL recommends a Mediterranean diet,^[20] which can reduce liver fat even without weight loss
• Active management of any coexisting features of MetS, for example, dysglycaemia/T2D, hypertension, dyslipidaemia, and abdominal obesity/increased waist circumference
• Ideally alcohol abstinence is advised, otherwise maintain alcohol intake within recommended limits
• Assess CV risk using QRISK3, and consider statin therapy, including those with abnormal baseline liver blood tests. Statins can be initiated as long as liver blood tests are <3x ULN^[21]
  • there is emerging evidence that statin use is associated with a reduction in liver cancer risk^[22]
• Coffee might help! 
  • there is evidence brewing that coffee is good for liver health, and decreases the risk of fibrosis, cirrhosis, and HCC in chronic liver disease, including MASLD^[23]
  • no specific recommendations have been made; however, a moderate intake of coffee of 3–5 cups a day may be beneficial^[24]
• There are no current licensed drug therapies for MASLD/MASH, however there is emerging and compelling evidence for pioglitazone, sodium–glucose cotransporter-2 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and the dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, tirzepatide^{[25] [26]}
  • NICE and EASL guidance suggest that pioglitazone can be used off-label in those without T2D for MASH
• Follow up in primary care:
  • if identified as intermediate or high risk, consider referral to secondary care gastroenterology for transient elastography (FibroScan)
  • ensure those with MASLD found to have a low risk of advanced fibrosis are under recall and reviewed regularly in primary care, using clinical judgement and the BSG guidance.

• Coffee consumption and the liver - the potential health benefits
• NAFLD, NASH and fatty liver disease

The European Association for the Study of the Liver:

• Non-alcoholic fatty liver disease (NAFLD): How you can reduce the risk for your liver and for other health issues?