Prevalence of Liver Fibrosis and its Association with Non-invasive Fibrosis and Metabolic Markers in Morbidly Obese Patients with Vitamin D Deficiency

Maria Luger, Renate Kruschitz, Christian Kienbacher, Stefan Traussnigg, Felix B Langer, Karin Schindler, Tanja Würger, Friedrich Wrba, Michael Trauner, Gerhard Prager, Bernhard Ludvik, Maria Luger, Renate Kruschitz, Christian Kienbacher, Stefan Traussnigg, Felix B Langer, Karin Schindler, Tanja Würger, Friedrich Wrba, Michael Trauner, Gerhard Prager, Bernhard Ludvik

Abstract

Background: Morbidly obese patients are at risk for non-alcoholic fatty liver disease (NAFLD) and vitamin D deficiency (VDD). Non-alcoholic steatohepatitis (NASH) is the progressive variant of NAFLD and can advance to fibrosis, cirrhosis, and liver cancer. We aimed to examine prevalence of liver fibrosis and its non-invasive predictors in bariatric patients with VDD (<75 nmol/l).

Methods: Baseline liver biopsy of a randomized controlled trial was performed in 46 patients with omega loop gastric bypass. Clinical, laboratory, and histological data were examined and tested with univariate and multivariable analysis.

Results: In total, 80 % were females, aged 42 (SD 13) years with BMI 44 (4) kg/m(2). Twenty-six percent had diabetes mellitus (DM) and 44 % metabolic syndrome (MeS). Seventy-two percent had NASH, 11 % simple steatosis, and 17 % normal liver. In total, 30 % demonstrated significant fibrosis (F ≥ 2) with 9 % of advanced (F3) and 4 % cirrhosis (F4). Increased stages of fibrosis were primarily associated with higher levels of HOMA2-insulin resistance (IR), procollagen type I propeptide (P1NP), lower osteocalcin, albumin-corrected calcium, parathyroid hormone, vitamin D, male sex, and higher age. Other independent risk factors for advanced fibrosis were MeS (OR = 9.3 [0.99-87.5], p = 0.052) and DM (OR = 12.8 [1.2-137.4], p = 0.035). The fibrosis FIB-4 index <10.62 and NAFLD fibrosis score <-26.93 had a negative predictive value of 100 and 96 %, respectively.

Conclusions: Liver fibrosis is frequent in morbidly obese patients with concurrent DM and/or MeS. Increased serum levels of IR, P1NP, lower osteocalcin, and VDD are clinically relevant predictors of fibrosis. Consequently, we suggest that patients with preoperative presence of these markers are at increased risk for liver fibrosis and should be monitored closely.

Trial registration: ClinicalTrials.gov NCT02092376.

Keywords: Bariatric surgery; Diabetes mellitus; Liver fibrosis; Metabolic syndrome; Vitamin D.

Conflict of interest statement

Compliance with Ethical StandardsInformed consent was obtained from each patient included in the study. The trial was approved by the local Ethical Committee of the Medical University of Vienna (Ref No.: 1899/2013) and the Austrian Competent Authority (Ref. No.: LCM-718280-0001) and conforms to the ethical guidelines of the 1975 Declaration of Helsinki [12]. Furthermore, the protocol was registered at clinicaltrials.gov (NCT02092376) and the European Clinical Trials Database (EudraCT: 2013-003546-16). The study methods are in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting randomized trials [13].DisclosuresThe authors ML, RK, CK, ST, FL, KS, TW, FW, and BL have no commercial associations that might be a conflict of interest in relation to this article. MT reports grants and personal fees from Albireo, Gilead, MSD, Falk, and Intercept, personal fees from Janssen and Novartis, and grants from Takeda outside the submitted work. In addition, MT is listed as a co-inventor in a patent on the Medical use of nor-UDCA licensed to Med Univ Graz. GP reports educational grant from Medtronic outside the submitted work.

Figures

Fig. 1
Fig. 1
Patients with normal serum levels of liver enzymes divided by those with NASH, significant fibrosis (F2-3), and cirrhosis (F4). Note: ASAT aspartate aminotransferase, ALAT alanine aminotransferase, γ-GT γ-glutamyl transferase, NASH non-alcoholic steatohepatitis, F2–F3 significant fibrosis, F4 cirrhosis
Fig. 2
Fig. 2
Receiver operating characteristic (ROC) curves of calculated non-invasive fibrosis markers FIB-4 index (a) and NAFLD fibrosis score (NFS) (b). Note: NAFLD non-alcoholic fatty liver disease
Fig. 3
Fig. 3
Prevalence of distinct histological forms of steatosis (a), non-alcoholic fatty liver disease (b), and fibrosis (c) according to the presence of diabetes mellitus in the study population. Note: DM type 2 diabetes mellitus, NAFLD non-alcoholic fatty liver disease, NASH non-alcoholic steatohepatitis
Fig. 4
Fig. 4
Receiver operating characteristic (ROC) curves of HOMA2-insulin resistance (a) and HbA1c (b). Note: HOMA2-IR homeostatic model assessment insulin resistance, HbA1c glycated hemoglobin

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