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}

}

@article{Cianci2022-xi,

title = {Prognostic non-invasive biomarkers for all-cause mortality in 

 non-alcoholic fatty liver disease: A systematic review and 

 meta-analysis},

author = {Nicole Cianci and Mohsan Subhani and Trevor Hill and Amardeep Khanna and Dong Zheng and Abhishek Sheth and Colin Crooks and Guruprasad P Aithal},

year  = {2022},

date = {2022-05-01},

journal = {World J. Hepatol.},

volume = {14},

number = {5},

pages = {1025\textendash1037},

publisher = {Baishideng Publishing Group Inc.},

abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents 

 a growing public health concern, with patients having higher 

 risk of morbidity and mortality. It has a considerably high 

 prevalence in the general population, estimated 20%-40% in 

 Europe, and is asymptomatic until late in the disease course. It 

 is therefore important to identify and validate tools that 

 predict hard outcomes such as mortality for use in clinical 

 practice in risk-stratifying NAFLD patients. AIM: To evaluate 

 available evidence on the use of non-invasive test(s) as 

 prognostic factors for mortality in NAFLD. METHODS: We performed 

 electronic searches of Medline and EMBASE (Ovid) until 7th 

 January 2021 of studies in NAFLD populations. Prognostic markers 

 included serum biomarkers, non-invasive scoring systems, and 

 non-invasive imaging. The population included all spectrums of 

 disease severity, including NAFLD and non-alcoholic 

 steatohepatitis (NASH). Outcomes included all-cause, and 

 cardiovascular mortality. All non-invasive tests were 

 synthesised in a narrative systematic review. Finally, we 

 conducted a meta-analysis of non-invasive scoring systems for 

 predicting all-cause and cardiovascular mortality, calculating 

 pooled hazard ratios and 95% confidence (STATA 16.1). RESULTS: 

 Database searches identified 2850 studies - 24 were included. 16 

 studies reported non-invasive scoring systems, 10 studies 

 reported individual biomarkers, and 1 study reported imaging 

 modalities. 4 studies on non-invasive scoring systems (6324 

 participants) had data available for inclusion in the 

 meta-analysis. The non-invasive scoring system that performed 

 best at predicting all-cause mortality was NAFLD fibrosis score 

 (NFS) [pHR 3.07 (1.62-5.83)], followed by fibrosis-4 index [pHR 

 3.06 (1.54-6.07)], BARD [pHR 2.87 (1.27-6.46)], and AST to 

 platelet ratio index [pHR 1.90 (1.32-2.73)]. NFS was also 

 prognostic of cardiovascular-related mortality [pHR 3.09 

 (1.78-5.34)]. CONCLUSION: This study reaffirms that non-invasive 

 scoring systems, especially NFS, are reliable prognostic markers 

 of all-cause mortality and cardiovascular mortality in NAFLD 

 patients. These findings can inform clinical practice in risk 

 stratifying NAFLD patients.},

keywords = {biomarkers, mortality, Non-invasive, Nonalcoholic fatty liver   disease, Nonalcoholic steatohepatitis, Prognosis},

pubstate = {published},

tppubtype = {article}

}

@article{Atallah2021-yd,

title = {Biomarkers of idiosyncratic drug-induced liver injury (DILI) - 

 a systematic review},

author = {Edmond Atallah and Cristiana Freixo and Ismael Alvarez-Alvarez and F J Cubero and Alexander L Gerbes and Gerd A Kullak-Ublick and Guruprasad P Aithal},

year  = {2021},

date = {2021-11-01},

journal = {Expert Opin. Drug Metab. Toxicol.},

volume = {17},

number = {11},

pages = {1327\textendash1343},

publisher = {Informa UK Limited},

abstract = {INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is 

 an unpredictable event, and there are no specific biomarkers 

 that can distinguish DILI from alternative explanations or 

 predict its clinical outcomes. AREAS COVERED: This systematic 

 review summarizes the available evidence for all biomarkers 

 proposed to have a role in the diagnosis or prognosis of DILI. 

 Following a comprehensive search, we included all types of 

 studies in humans. We included DILI cases based on any threshold 

 criteria but excluded intrinsic DILI, commonly caused by 

 paracetamol overdose. We classified studies into diagnostic and 

 prognostic categories and assessed their methodological quality. 

 After reviewing the literature, 14 studies were eligible. EXPERT 

 OPINION: Diagnostic studies were heterogeneous with regard to 

 the study population and outcomes measured. Prognostic models 

 were developed by integrating novel biomarkers, risk scores, and 

 traditional biomarkers, which increased their prognostic ability 

 to predict death or transplantation by 6 months. This systematic 

 review highlights the case of need for non-genetic biomarkers 

 that distinguish DILI from acute liver injury related to 

 alternative etiology. Biomarkers with the potential to identify 

 serious adverse outcomes from acute DILI should be validated in 

 independent prospective cohorts with a substantial number of 

 cases.},

keywords = {biomarkers, DILI, Drug-induced liver injury, hepatotoxicity, systematic review},

pubstate = {published},

tppubtype = {article}

}