TY  - JOUR
A1  - John, Katharina
A1  - Franck, Martin
A1  - Al Aoua, Sherin
A1  - Rau, Monika
A1  - Huber, Yvonne
A1  - Schattenberg, Joern M.
A1  - Geier, Andreas
A1  - Bahr, Matthias J.
A1  - Wedemeyer, Heiner
A1  - Schulze-Osthoff, Klaus
A1  - Bantel, Heike
T1  - Non-invasive detection of fibrotic NASH in NAFLD patients with low or intermediate FIB-4
JF  - Journal of Clinical Medicine
N2  - Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (n = 103) and validation (n = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification.
KW  - apoptosis
KW  - biomarker
KW  - fibrosis
KW  - FIB-4
KW  - NAFLD
KW  - NASH
KW  - keratin-18
KW  - M30
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281824
SN  - 2077-0383
VL  - 11
IS  - 15
ER  - 
TY  - JOUR
A1  - Becker, Philip P.
A1  - Rau, Monika
A1  - Schmitt, Johannes
A1  - Malsch, Carolin
A1  - Hammer, Christian
A1  - Bantel, Heike
A1  - Müllhaupt, Beat
A1  - Geier, Andreas
T1  - Performance of serum microRNAs -122, -192 and -21 as biomarkers in patients with non-alcoholic steatohepatitis
JF  - PLoS ONE
N2  - Objectives 
Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers. 

Methods 
Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH. 

Results 
The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%). 

Conclusions 
Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.
KW  - fatty liver disease
KW  - independent marker
KW  - expression
KW  - injury
KW  - NAFLD
KW  - circulating micrornas
KW  - caspase activation
KW  - fibrosis
KW  - miR-122
KW  - apoptosis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145147
VL  - 10
IS  - 11
ER  -