Visual summary Testing for non-alcoholic fatty liver disease

The term “Non-alcoholic fatty liver disease” (NAFLD) encompasses a spectrum of pathologic conditions, ranging from non-alcoholic fatty liver (NAFL) to steatohepatitis (NASH), fibrosis, and cirrhosis. This flow diagram offers a pragmatic approach to the diagnosis and monitoring of NAFLD in asymptomatic adult patients.

Recommended amounts are less than Abnormal Alcohol consumption 14 units for both men liver function within recommended and women, spread tests amounts over a week, with + 2–3 alcohol-free days every week

History and Red flags: Consider admission Drug-induced liver injury examination or urgent referral Consider referral to hepatology if patient has a history of drug exposure, such as: Consider alternative diagnoses Suspected malignancy Ascites such as effects of medication, infection, or nutritional Jaundice Encephalopathy Sepsis Valproic acid Oestrogens Tamoxifen Valproic acid problems. Evidence of disordered clotting Haematemesis Tetracycline Amiodarone Perhexiline maleate Valproic acid ALT or ALP very high (5x upper limit of normal) Methotrexate 4,4’-diethylaminoethoxyhexesterol Valproic acid Persistently low albumin or platelets Rapid deterioration Chloroquine L-asparaginase Corticosteroids

Non-invasive liver screen (NILS) Refer to Hepatology if NILS Consider non-hepatic Liver tests yield positive results for: causes for raised ALT: Blood tests ultrasound Immunoglobulins raised Hepatitis B or C Thyroid diseases High ferritin and high transferrin saturation Coeliac disease Undertaking a liver biopsy is a risky, potentially painful procedure. Non-invasive techniques can be Autoimmune liver screen (Primary biliary cholangitis) Muscle diseases, such as used to assess the presence of both hepatic Low caeruloplasmin Low alpha 1 anti-trypsin protein polymyositis, heavy exercise steatosis and fibrosis.

Dominant ALP abnormality Dominant ALT abnormality Dominant bilirubin abnormality

Normal ALT, ALP, INR, and albumin

Consider Gilbert’s GGT normal GGT raised Consider cirrhosis if: Ultrasound ALT or ALP syndrome if: Albumin persistently low confirms raised presence of Conjugated Spleen size increased hepatic bilirubin <10 μmol/L Platelets low INR high steatosis Bilirubin high Consider Consider Refer to hepatology haemolysis if: Vitamin D de ciency Refer to general Unconjugated surgery if gallbladder Refer to Bone disease bilirubin high or bile duct stones hepatology Refer to Third trimester detected on imaging pregnancy haematology Anaemia Varies with age Rapidly growing adolescents have Ultrasound confirms presence up to 2 fold increase of hepatic steatosis If hepatic steatosis is detected as an incidental finding, it is important to follow the flow NAFLD diagram, including undertaking non-alcoholic liver screen (NILS) Once NAFLD has been confirmed it is important to assess liver disease severity with assessment of liver fibrosis

Investigate severity of liver fibrosis Although biopsy is the most accurate way of staging fibrosis, it is usually reserved for patients who are most likely to have substantial fibrosis or where there is diagnostic uncertainty. If available, the enhanced Liver Fibrosis test (ELF) is preferred by NICE guidelines in the UK. If it is not available, use another non invasive test as recommended by European and American guidelines.

ELF test available No ELF test available

ELF test Check non-invasive markers of hepatic fibrosis which can rule out presence of advanced fibrosis, such as: Enhanced Liver Fibrosis (ELF) blood test FIB4 score > 2.67 NAFLD brosis score > 0.676

Second-line tests for hepatic fibrosis, such as: Transient elastography Other imaging (FibroScan) > 8.7 kPA techniques <7.7 7.8–10.5 > 10.5 No Liver May indicate a Likely advanced Fibrosis degree of liver fibrosis or fibrosis cirrhosis Positive Negative Abnormal test results, highly Test results do not suggest suggestive of advanced advanced fibrosis or fibrosis or cirrhosis cirrhosis

Consider further investigations, such as: Treatment and long Liver biopsy Repeat non-invasive Refer to term Repeat non-invasive liver fibrosis test hepatology Upper gastrointestinal monitoring liver fibrosis test every 2-3 years endoscopy every 2-3 years

Lifestyle advice Control cardiometabolic Cardiovascular risk assessment Patients with NAFLD can benefit from risk factors making heathier lifestyle choices. Offer NAFLD may present with or without Oer annual monitoring for patients education and advice irrespective of these commonly co-existing being treated for diabetes, hypertension whether referral is needed or not. conditions. These are associated or with statins to decrease CVD risk with increased severity of NAFLD Weight loss and and increased risk of liver fibrosis physical activity Type 2 diabetes Especially if the patient Patients with biopsy-proven NASH Obesity (BMI ≥ 30) is overweight or obese Consider pioglitazone or vitamin E after consultation with specialists, Metabolic syndrome (3+ cardiometabolic risk factors) if not contraindicated.

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