Publications

@article{Lonsmann2023-pc,

title = {Biomarkers of type IV collagen turnover reflect disease 

 activity in patients with early-stage non-alcoholic fatty liver 

 (NAFL)},

author = {Ida L\onsmann and Jane I Grove and Asma Haider and Philip Kaye and Morten A Karsdal and Diana J Leeming and Guruprasad P Aithal},

year  = {2023},

date = {2023-08-01},

journal = {Biology (Basel)},

volume = {12},

number = {8},

abstract = {BACKGROUND: Identification of progressive liver disease 

 necessitates the finding of novel non-invasive methods to 

 identify and monitor patients in need of early intervention. 

 Investigating patients with early-liver injury may help identify 

 unique biomarkers. Early-liver injury is characterized by 

 remodeling of the hepatocyte basement membrane (BM) of the 

 extracellular matrix. Thus, we quantified biomarkers targeting 

 two distinct neo-epitopes of the major BM collagen, type IV 

 collagen (PRO-C4 and C4M), in patients spanning the non-alcoholic 

 fatty liver disease (NAFLD) spectrum. METHODS: We evaluated 

 PRO-C4 and C4M in a cross-sectional study with 97 patients with 

 NAFLD confirmed on histology. Serological levels of PRO-C4 and 

 C4M were quantified using validated competitive enzyme-linked 

 immunosorbent assays (ELISA). Using the fatty liver inhibition of 

 progression (FLIP) algorithm, we stratified patients into two 

 groups: non-alcoholic fatty liver (NAFL) and non-alcoholic 

 steatohepatitis (NASH). Biomarker levels were investigated in the 

 two groups in patients stratified by the NAFLD activity score 

 (NAS). In both groups, biomarker measurements were analyzed in 

 relation to histological scorings of steatosis, inflammation, 

 ballooning, and fibrosis. RESULTS: Patients had a body mass index 

 (BMI) of 30.9 $±$ 5.6 kg/m2, age of 53 $±$ 13 years and a NAS 

 range of 1-8. Upon stratification by FLIP, the NASH patients had 

 higher platelets, ALT, and AST levels than the NAFL group. Both PRO-C4 (p = 0.0125) and C4M (p = 0.003) increased with increasing 

 NAS solely within the NAFL group; however, a large variability 

 was present in the NASH group. Furthermore, both markers were significantly associated with lobular inflammation (p = 0.020 and p = 0.048) and steatosis (p = 0.004 and p = 0.015) in patients 

 with NAFL. CONCLUSIONS: This study found that type IV collagen 

 turnover increased with the increase in NAS in patients with 

 NAFL; however, this was not the case in patients with NASH. These 

 findings support the assessments of the BM turnover using 

 biomarkers in patients with early-disease development. These 

 biomarkers may be used to track specific processes involved in 

 the early pathobiology of NAFL.},

keywords = {basement membrane, biomarkers, collagen turnover, extracellular matrix, NAFLD},

pubstate = {published},

tppubtype = {article}

}