Referral of Patients with Non-alcoholic Fatty Liver Disease with Significant Fibrosis from Primary Care to Secondary Care in Belgium - European Medical Journal

Referral of Patients with Non-alcoholic Fatty Liver Disease with Significant Fibrosis from Primary Care to Secondary Care in Belgium

2 Mins
EMJ Hepatology 9.1 Feature Image
*Leen JM Heyens,1-3 Dana Busschots,1,3 Judith Wellens,4 Marlies Devos,5 Luc Present,6 Birgitte Schoenmakers,7 Kitty De Munck,8 Eva Rubens,8 Katrien Joris,8 Roy Remmen,1,9 Anouk Bongaerts,10 Karen Breure,10 Frederik Vanstraelen,10 Valerie Vos,10 Lisa Vanbrabant,11 Yoni Groenendaels,11 Liesbeth Vernijns,10 Anneleen Robaeys,11 Thomas De Somer,12 Ger Koek,2,13 Sven Francque,14,15 Christophe Van Steenkiste,12,15 Geert Robaeys1,3,16

Heyens is funded by the Fonds Wetenschappelijk Onderzoek (FWO), Flanders. Busschots has received travel grants from AbbVie and Gilead Sciences; and has received research grants from Gilead. Robaeys has received research grants from AbbVie, Janssen Pharmaceuticals, and MSD; and has received consultancy agreements for AbbVie, BMS, Gilead Sciences, and MSD. All other co-authors have declared no conflicts of interest.


The authors would like to thank the general practitioners and nurses for their collaboration in patient recruitment.

EMJ Hepatol. ;9[1]:30-31. Abstract Review No. AR2..
Belgium, non-alcoholic fatty liver disease, primary care, significant fibrosis.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.


Non-alcoholic fatty liver disease (NAFLD) is becoming the most frequent cause of chronic liver disease worldwide.1 The stage of fibrosis has been identified as the most important predictor of prognosis. Patients with significant fibrosis have a higher risk of developing Type 2 diabetes mellitus, cardiovascular disease, and extra-hepatic malignancies.2 However, the majority of fibrotic NAFLD patients are currently undetected. As the general practitioner’s (GP) outpatient clinic is usually their first contact in the health care system, they can play an essential role in the identification of this group of patients. There are several non-invasive tests available that can be used in primary care. For example, the Fibrosis-4 (FIB-4) index has been proposed by Newsome et al. to predict fibrosis as it is based on the routine blood parameters aspartate aminotransferase, alanine aminotransferase, age, and thrombocytes.3


In their current study, the authors aim to verify if the FIB-4 is a valuable tool to identify NAFLD patients with significant fibrosis or higher as compared to vibration-controlled transient elastography (VCTE) by FibroScan® (Echosens, France) as a reference method. In a prospective study in five Belgian GP practices, people were invited for VCTE measurement. Based on the most recent laboratory data from the electronic patient file, the FIB-4 was calculated. To grade the VCTE measurements, the authors used the cut-off values as stated by the Belgian Association for the Study of the Liver (BASL).4 The risk of significant fibrosis determined by the FIB-4 was based on a cut-off value ≥1.3 for people younger than 65 years and ≥2.0 for people older than 65 years.


A first analysis of the data revealed that of the 292 people who were screened, 248 (84.9%) had all the values available to calculate the FIB-4. The authors found that 64 (26.8%) of those people had a high FIB-4 index. However, when compared to the VCTE measurements, 52 (77.6%) people were graded F0–F1 (no or mild liver scarring), while the FIB-4 index indicated an increased risk for significant fibrosis. The calculated area under the receiving operating curve with VCTE as reference was only 0.632. As a good area under the receiving operating curve is usually considered to be higher than 0.700, the authors concluded that the usage of FIB-4 in primary care in Belgium is only able to detect NAFLD patients with significant fibrosis moderately.


The authors, therefore, suggest using other test strategies or a sequential combination. A disadvantage of the other available non-invasive tests is the usage of not readily available parameters. For example, the NAFLD Fibrosis Score (NFS) uses albumin. The addition of these parameters increases the costs and is therefore not preferred. Another possibility, as has been proposed by Shah et al., is to use different cut-off values for the FIB-4.5 Nevertheless, the authors are still of the opinion that the FIB-4 is going to play a key in the referral from primary to secondary or tertiary care.

Tanaka N et al. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol. 2019;25(2):163-77. Heyens LJM et al. Liver fibrosis in non-alcoholic fatty liver disease: from liver biopsy to non-invasive biomarkers in diagnosis and treatment. Front Med (Lausanne). 2021;8:615978. Newsome PN et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6-19. Francque S et al. The Belgian Association for Study of the Liver guidance document on the management of adult and paediatric non-alcoholic fatty liver disease. Acta Gastroenterol Belg. 2018;81(1):55-81. Shah S et al. FIB-4 cut-off of 1.3 may be inappropriate in a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2020;73(1):216-7.

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