The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care

Wolf Peter Hofmann; Peter Buggisch; Lisa Schubert; Nektarios Dikopoulos; Jeannette Schwenzer; Marion Muche; Gisela Felten; Renate Heyne; Patrick Ingiliz; Anna Schmidt; Kerstin Stein; Heiner Wedemeyer; Thomas Berg; Johannes Wiegand; Frank Lammert; Stefan Zeuzem; Jörn M Schattenberg

doi:10.1016/j.jhepr.2020.100168

The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care

JHEP Rep. 2020 Aug 4;2(6):100168. doi: 10.1016/j.jhepr.2020.100168. eCollection 2020 Dec.

Authors

Wolf Peter Hofmann^{1

2}, Peter Buggisch^{2

3}, Lisa Schubert^{1

4}, Nektarios Dikopoulos⁵, Jeannette Schwenzer⁶, Marion Muche⁴, Gisela Felten⁷, Renate Heyne⁸, Patrick Ingiliz⁹, Anna Schmidt¹⁰, Kerstin Stein¹¹, Heiner Wedemeyer¹², Thomas Berg¹³, Johannes Wiegand¹³, Frank Lammert¹⁴, Stefan Zeuzem¹⁵, Jörn M Schattenberg^{16

17}

Affiliations

¹ Gastroenterologie am Bayerischen Platz, Berlin, Germany.
² Association of Gastroenterologists in Private Practice (Berufsverband Niedergelassener Gastroenterologen Deutschlands), Ulm, Germany.
³ IFI Institut für interdisziplinäre Medizin, Hamburg, Germany.
⁴ Medical Department (Gastroenterology, Infectiology, Rhumatology) Charité Campus Benjamin Franklin, Berlin, Germany.
⁵ Gastroenterologische Schwerpunktpraxis, Dornstadt, Germany.
⁶ Bauchzentrum Biesdorf, Berlin, Germany.
⁷ Gastroenterologische Praxis Herne, Herne, Germany.
⁸ Leberzentrum am Checkpoint, Berlin, Germany.
⁹ Zentrum für Infektiologie Prenzlauer Berg, Berlin, Germany.
¹⁰ Magen-Darm-Zentrum Wiener Platz, Cologne, Germany.
¹¹ Praxis für Infektiologie und Hepatologie Magdeburg, Magdeburg, Germany.
¹² Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
¹³ Division of Hepatology, Department of Medicine II, Leipzig University Hospital, Leipzig, Germany.
¹⁴ Department of Medicine II, Saarland University Hospital, Homburg, Germany.
¹⁵ Department of Internal Medicine, Goethe University Hospital Frankfurt, Frankfurt, Germany.
¹⁶ I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
¹⁷ Metabolic Liver Research Program, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.

Abstract

Background & aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care.

Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months.

Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%.

Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients.

Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.

Keywords: ALT, alanine aminotransferase; APRI, aspartate-aminotransferase-to-platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; CAP, controlled attenuation parameter; CVE, cardiovascular event; Co-morbidities; FAST, FibroScan-AST; FIB-4, fibrosis-4; FLAG, Fatty Liver Assessment in Germany; GGT, gamma-glutamyltransferase; GLP-1, glucagon-like peptide-1; LSM, liver stiffness measurement; Liver fibrosis; Metabolic syndrome; NAFL, non-alcoholic fatty liver; NAFLD; NAFLD, non-alcoholic fatty liver disease; NASH; NASH, non-alcoholic steatohepatitis; Real world; T2DM, type 2 diabetes mellitus.