Performance of non-invasive fibrosis scores in non-alcoholic fatty liver disease with and without morbid obesity

International Journal of Obesity ARTICLE www.nature.com/ijo OPEN Performance of non-invasive fibrosis scores in non-alcoholic fatty liver disease with and without morbid obesity ✉ Andreas Drolz 1,3 , Stefan Wolter2,3, Malte H. Wehmeyer1, Felix Piecha1, Thomas Horvatits1, Julian Schulze zur Wiesch1, 1 Ansgar W. Lohse , Oliver Mann2 and Johannes Kluwe1 © The Author(s) 2021 BACKGROUND: Non-invasive scores, such as the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), are increasingly used for liver fibrosis assessment in patients with NAFLD. The aim of this study was to assess the applicability and reliability of noninvasive fibrosis scores in NAFLD patients with and without morbid obesity. METHODS: Three hundred sixty-eight patients with biopsy-proven NAFLD identified between January 2012 and December 2015 were studied; 225 with morbid obesity (biopsy obtained during bariatric surgery) and 143 patients without (termed as “conventional”). RESULTS: Median age was 47 years, 57% were female. Median body mass index (BMI) was 42.9 kg/m2 with significant differences between our conventional and morbidly obese patients (BMI 29.0 vs. 50.8 kg/m2, p < 0.001). Overall, 42% displayed mild/moderate and 16% advanced liver fibrosis (stage III/IV). All tested scores were significantly linked to fibrosis stage (p < 0.001 for all). FIB-4 (AUROC 0.904), APRI (AUROC 0.848), and NFS (AUROC 0.750) were identified as potent predictors of advanced fibrosis, although NFS overestimated fibrosis stage in morbid obesity. Limiting BMI to a maximum of 40 kg/m2 improved NFS’ overall performance (AUROC 0.838). FIB-4 > 1.0 indicated high probability of advanced fibrosis (OR = 29.1). FIB-4 predicted advanced fibrosis independently from age, sex, BMI, and presence of morbid obesity. CONCLUSIONS: Our data suggest that FIB-4 score is an accurate predictor of advanced fibrosis in NAFLD throughout all BMI stages. Without adjustment, NFS tends to overestimate fibrosis in morbidly obese NAFLD patients. This problem may be solved by implementation of an upper BMI limit (for NFS) or adjustment of diagnostic thresholds. International Journal of Obesity (2021) 45:2197–2204; https://doi.org/10.1038/s41366-021-00881-8 INTRODUCTION As a consequence of the worldwide epidemic of obesity, diabetes mellitus, and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease [1–4] with reported prevalence rates of up to 46% [5]. Without appropriate treatment, NAFLD and especially nonalcoholic steatohepatitis (NASH) can progress to fibrosis and ultimately cirrhosis. As a consequence of these developments, NASH has become the second leading etiology of liver disease in adults awaiting transplantation in the United States [6], and a major cause of hepatocellular carcinoma (HCC) [7]. Histological confirmation is considered the gold standard for diagnosis and staging of the disease [8, 9]. Stage of liver fibrosis is of paramount importance as it has been identified as an independent predictor of liver-related (and all-cause) mortality in patients with NAFLD in various studies [10–12]. Thus, detection of liver fibrosis is a crucial diagnostic step to stratify the individual risk of patients with NAFLD. Several non-invasive tools have been introduced that allow assessment of fibrosis stage even without biopsy [9]. Transient elastography is among the most widely used techniques for noninvasive fibrosis assessment, but shows some limitations in morbidly obese patients [13, 14]. Fibrosis scores based on patient characteristics, anthropometric measurements, and laboratory parameters are increasingly used, and are considered as feasible alternative to imaging techniques, especially for exclusion of advanced fibrosis (stage III/IV) [9]. It has been repeatedly demonstrated that non-invasive fibrosis scores accurately predict advanced fibrosis in NAFLD [15–18]. To our knowledge, however, the value of non-invasive fibrosis scores with respect to body mass index (BMI) has not been evaluated. The aim of this study was to assess the performance of different non-invasive scoring tools for liver fibrosis in NAFLD patients of different weight classes. For this purpose, we have evaluated noninvasive liver fibrosis scoring tools in a cohort of overweight or moderately obese (class I) NAFLD patients and in a NAFLD cohort with morbid or super (class III) obesity. MATERIALS AND METHODS Patients with well-characterized and biopsy-confirmed NAFLD were retrospectively studied at the University Medical Center HamburgEppendorf. All patients underwent biopsy between January 2012 and December 2015. Our patient population consisted of 143 NAFLD patients 1 I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3These authors contributed equally: Andreas Drolz, Stefan Wolter. ✉email: Received: 7 March 2021 Revised: 16 May 2021 Accepted: 9 June 2021 Published online: 24 June 2021 A. Drolz et al. 2198 Table 1. Characteristics of 368 patients with non-alcoholic fatty liver disease. Parameter NAFLD patients (n = 368) Overall Conventional cohort (n = 143) Morbidly obese cohort (n = 225) p value Age, years (IQR) 47 (35–56) 52 (35–60) 45 (35–51) <0.001 Sex (females), n (%) 210 (57) 62 (43) 148 (66) <0.001 <0.01 Concomitant diseases Preexisting diseases Diabetes mellitus, n (%) 133 (36) 39 (27) 94 (42) Arterial hypertension, n (%) 226 (61) 68 (48) 158 (70) <0.001 Hyperlipidemia, n (%) 182 (50) 28 (20) 154 (68) <0.001 Impaired fasting glucose or diabetes, n (%) 179 (49) 58 (41) 121 (54) <0.05 Total cholesterol ≥200 mg/dl, n (%) 143 (39) 64 (45) 79 (35) 0.064 Triglycerides ≥170 mg/dl, n (%) 203 (55) 76 (53) 127 (56) 0.535 Findings during evaluation for biopsy 1234567890();,: Body mass Height, m (IQR) 172 (165–179) 174 (164–181) 172 (165–178) 0.182 Weight, kg (IQR) 126 (94–158) 87 (75–100) 147 (128–170) <0.001 <0.001 BMI (kg/m2) 42.9 (31.1–53.2) 29.0 (26.2–32.5) 50.8 (44.7–56.8) Overweight, n (%) 57 (16) 57 (40) 0 Obesity, n (%) 285 (77) 60 (42) 226 (100) Excess body weight, kg (IQR) 61 (26–92) 21 (12–31) 84 (65–105) <0.001 1 (0–1) 1 (0–3) 0 (0–1) <0.001 Biopsy findings Fibrosis grade (IQR) No fibrosis, n (%) 156 (42) 36 (25) 120 (53) Grade 1, n (%) 122 (33) 41 (29) 81 (36) Grade 2, n (%) 32 (9) 21 (15) 11 (5) Grade 3, n (%) 22 (6) 19 (13) 3 (1) Grade 4/cirrhosis, n (%) 36 (10) 26 (18) 10 (5) Liver fat content, % (IQR) 30 (10–50) 20 (10–40) 40 (15–60) <0.01 NAS score (IQR)a 4 (3–5) 4 (3–5) 4 (3–5) <0.01 AST, IU/l (IQR) 29 (19–50) 51 (33–73) 22 (16–31) <0.001 ALT, IU/l (IQR) 41 (25–72) 75 (50–133) 29 (19–44) <0.001 Gamma-glutaryltransferase, IU/l (IQR) 51 (30–113) 113 (66–238) 35 (25–57) <0.001 Bilirubin, mg/dl (IQR)b 0.5 (0.4–0.6) 0. 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