Screening at-risk patients for NAFLD

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver disease. The FIB-4 score can be used to identify at-risk patients with NAFLD and, if necessary, refer them for further hepatologic evaluation. It is a simple and cost-effective screening method that is suitable for the primary care setting.

While screening the general population for NAFLD cannot be recommended, it is advised to screen at-risk patients – especially those with type 2 diabetes, metabolic syndrome, BMI >30 kg/m² or arterial hypertension – for the presence of NAFLD, particularly if elevated transaminases are present [1,2]. In the vast majority of cases (approx. 90%), NAFLD develops on the basis of a metabolic syndrome. NAFLD patients usually have central obesity and other components of a metabolic syndrome. Due to the serious consequences of progressive liver fibrosis and the frequency of NAFLD, a screening method that makes economic sense and is easy to implement is of great importance.

Risk of carcinoma is increased with advanced fibrosis

The extent of developing liver fibrosis is the most important risk factor for NAFLD-related morbidity and mortality. Further structural remodeling of the liver tissue can lead to the development of liver fibrosis or cirrhosis, the stage of which is decisive for the prognosis [1–3]. Due to the increased risk of hepatocellular carcinoma (HCC) and, less frequently, intrahepatic cholangiocarcinoma, regular screening is recommended for NAFLD with advanced fibrosis according to the current s2k guideline [4–6]. The FIB-4 score is a non-invasive screening score that is used to identify risk constellations (advanced liver fibrosis). It is a simple and cost-effective method based on standard laboratory parameters. The FIB-4 score can be calculated automatically from the routine laboratory data ALAT, ASAT and thrombocytes. Due to its ease of implementation, it is a suitable tool for identifying at-risk patients with NAFLD in primary care. This is emphasized in the current version of the S2k guideline on NAFLD [1]. If inflammatory characteristics are added to NAFLD, steatohepatitis (NASH, non-alcoholic steatohepatitis) can develop. NASH is one of the leading etiologic factors for HCC and the diagnosis latency is a prognostically relevant factor [7]. It is recommended that patients with liver cirrhosis be screened every 6 months using imaging to detect carcinoma at a treatable stage [8].

Treat underlying diseases or comorbidities

There is currently no medication approved for the indication NAFLD. However, there are approved drugs for numerous typical concomitant diseases of NAFLD – such as type 2 diabetes, obesity, lipometabolic disorders – some of which have beneficial effects on NAFLD. Therefore, clear drug recommendations can be given for NAFLD depending on comorbidities and fibrosis stages. For example, glucagon-like peptide 1 (GLP1) receptor agonists have been shown to have beneficial effects on NAFLD in patients with type 2 diabetes (in combination with metformin) or obesity (as monotherapy) [9]. In obesity, bariatric surgery has also shown favorable long-term effects on both liver-associated and extrahepatic morbidity and mortality in NAFLD [10]. However, the guideline points out that metabolic surgery should not be performed on obese NAFLD patients with decompensated cirrhosis and/or portal hypertension [1].

Lifestyle modification as an important component

The lifestyle recommendations are propagated in the current NAFLD guideline as an important basis for any NAFLD treatment. Specific recommendations for NAFLD/NASH include [1,2,11]

• Weight normalization: overweight or obese NAFLD patients should reduce their weight by at least 5% (even by 10% to improve fibrosis), preferably through a hypocaloric diet
• Dietary recommendations: prefer Mediterranean diet, avoid sugary drinks (especially those containing fructose), sweets and snacks, prefer low-carbohydrate and high-protein diets, reduce or stop alcohol consumption, coffee consumption recommended
• Physical activity: at least 3 hours of aerobic exercise per week

It remains to be seen whether there will also be drug therapy options for the NAFLD/NASH indication in the future. The guideline mentions several active substances that are being investigated in phase III registration studies [1]: Obeticholic acid, resmetirome (selective thyroid hormone receptor-β agonist), aramchol (fatty acid-bile acid conjugate, which acts as a partial inhibitor of hepatic stearoyl-CoA desaturase), lanifbranor (pan-PPAR agonist), semaglutide (GLP1 receptor agonist) and belapectin (galectin-3 inhibitor).

Literature:

1. Roeb E, et al: Updated S2k guideline non-alcoholic fatty liver disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) April 2022 – AWMF registry number: 021-025.
2. Tacke F, Roeb E, Canbay A: The most important innovations in the updated S2k guideline on non-alcoholic fatty liver disease of the DGVS. Z Gastroenterol 2022; 60: 1-3.
3. Dulai PS, et al.: Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017; 65: 1557–1565.
4. Kanwal F, et al: Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology 2018; 155: 1828-1837.
5. Wongjarupong N, et al: Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis. BMC Gastroenterology 2017; 17: 149-156.
6. S3 guideline Diagnostics and therapy of hepatocellular carcinoma and biliary carcinoma. August 2023 – AWMF registration number: 032-053 OL
7. Vieira Barbosa J, Lai M: Nonalcoholic Fatty Liver Disease Screening in Type 2 Diabetes Mellitus Patients in the Primary Care Setting. Hepatol Commun 2020; 5(2): 158-167.
8. McGlynn KA, Petrick JL, London WT: Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis 2015; 19: 223-238.
9. Newsome PN, et al: A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021; 384 (12): 1113-1124.
10. Aminian A, et al: Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis. JAMA 2021; 326 (20): 2031-2042.
11. Younossi ZM, Corey KE, Lim JK: AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology 2021; 160 (3): 912-918.
12. Medical University of Graz: NAFLD, Non-Alcoholic Fatty Liver Disease, https://gastroenterologie.medunigraz.at/forschung/leberversagen/nafld,(last accessed 12.06.2024).