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{Sherry2023-op,

title = {Physical activity is inversely associated with hepatic 

 fibro-inflammation: A population-based cohort study using UK 

 Biobank data},

author = {Aron P Sherry and Scott A Willis and Thomas Yates and William Johnson and Cameron Razieh and Jack A Sargeant and Sundus Malaikah and David J Stensel and Guruprasad P Aithal and James A King},

year  = {2023},

date = {2023-01-01},

journal = {JHEP Rep.},

volume = {5},

number = {1},

pages = {100622},

publisher = {Elsevier BV},

abstract = {Background \& Aims: Physical activity (PA) is recommended in the 

 management of non-alcoholic fatty liver disease (NAFLD) given 

 its beneficial effects on liver fat and cardiometabolic risk. 

 Using data from the UK Biobank population-cohort, this study 

 examined associations between habitual PA and hepatic 

 fibro-inflammation. Methods: A total of 840 men and women aged 

 55-70 years were included in this cross-sectional study. Hepatic 

 fibro-inflammation (iron-corrected T1 [cT1]) and liver fat were 

 measured using MRI, whilst body fat was measured using 

 dual-energy X-ray absorptiometry. PA was measured using 

 accelerometry. Generalised linear models examined associations 

 between PA (light [LPA], moderate [MPA], vigorous [VPA], 

 moderate-to-vigorous [MVPA] and mean acceleration) and hepatic 

 cT1. Models were fitted for the whole sample and separately for 

 upper and lower median groups for body and liver fat. Models 

 were adjusted for sociodemographic and lifestyle variables. 

 Results: In the full sample, LPA (-0.08 ms [-0.12 to -0.03]), 

 MPA, (-0.13 ms [-0.21 to -0.05]), VPA (-1.16 ms [-1.81 to 

 -0.51]), MVPA (-0.14 ms [-0.21 to -0.06]) and mean acceleration 

 (-0.67 ms [-1.05 to-0.28]) were inversely associated with 

 hepatic cT1. With the sample split by median liver or body fat, 

 only VPA was inversely associated with hepatic cT1 in the upper 

 median groups for body (-2.68 ms [-4.24 to -1.13]) and liver fat 

 (-2.33 [-3.73 to -0.93]). PA was unrelated to hepatic cT1 in the 

 lower median groups. Conclusions: Within a population-based 

 cohort, device-measured PA is inversely associated with hepatic 

 fibro-inflammation. This relationship is strongest with VPA and 

 is greater in people with higher levels of body and liver fat. 

 Lay summary: This study has shown that people who regularly 

 perform greater amounts of physical activity have a reduced 

 level of inflammation and fibrosis in their liver. This 

 beneficial relationship is particularly strong when more intense 

 physical activity is undertaken (i.e., vigorous-intensity), and 

 is most visible in individuals with higher levels of liver fat 

 and body fat.},

keywords = {cT1, dual-energy X-ray absorptiometry, DXA, Exercise, iron-corrected T1, light   physical activity, Liver fat, LPA, milliseconds, moderate physical activity, moderate-to-vigorous physical activity, MPA, ms, MVPA, NAFLD, NASH, non-alcoholic   steatohepatitis, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Obesity, PA, PDFF, physical activity, proton density fat fraction, vigorous physical activity, VPA},

pubstate = {published},

tppubtype = {article}

}

@article{Vijay2022-jr,

title = {Development of food group tree-based analysis and its 

 association with non-alcoholic fatty liver disease (NAFLD) and 

 co-morbidities in a south Indian population: A large 

 case-control study},

author = {Amrita Vijay and Amina Al-Awadi and Jane Chalmers and Leena Balakumaran and Jane I Grove and Ana M Valdes and Moira A Taylor and Kotacherry T Shenoy and Guruprasad P Aithal},

year  = {2022},

date = {2022-07-01},

journal = {Nutrients},

volume = {14},

number = {14},

pages = {2808},

publisher = {MDPI AG},

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

 global problem growing in parallel to the epidemics of obesity 

 and diabetes, with South Asians being particularly susceptible. 

 Nutrition and behaviour are important modifiers of the disease; 

 however, studies to date have only described dietary patterns 

 and nutrients associated with susceptibility to NAFLD. METHODS: 

 This cross-sectional case-control study included 993 NAFLD 

 patients and 973 healthy controls from Trivandrum (India). 

 Dietary data was collected using a locally validated food 

 frequency questionnaire. A tree-based classification categorised 

 2165 ingredients into three levels (food groups, sub-types, and 

 cooking methods) and intakes were associated with clinical 

 outcomes. RESULTS: NAFLD patients had significantly higher 

 consumption of refined rice, animal fat, red meat, refined 

 sugar, and fried foods, and had lower consumption of vegetables, 

 pulses, nuts, seeds, and milk compared to controls. The 

 consumption of red meat, animal fat, nuts, and refined rice was 

 positively associated with NAFLD diagnosis and the presence of 

 fibrosis, whereas consumption of leafy vegetables, fruits, and 

 dried pulses was negatively associated. Fried food consumption 

 was positively associated with NAFLD, whilst boiled food 

 consumption had a negative association. Increased consumption of 

 animal fats was associated with diabetes, hypertension, and 

 cardiovascular outcomes among those with NAFLD, whereas 

 consumption of wholegrain rice was negatively associated with 

 these clinical-related outcomes. CONCLUSIONS: The tree-based 

 approach provides the first comprehensive method of classifying 

 food intakes to enable the identification of specific dietary 

 factors associated with NAFLD and related clinical outcomes. 

 This could inform culturally sensitive dietary guidelines to 

 reduce risk of NAFLD development and/or its progression.},

keywords = {case-control, co-morbidities, dietary   factors, food groups, NAFLD, South Asians},

pubstate = {published},

tppubtype = {article}

}

@article{Thiagarajan2021-rh,

title = {Metabolic imaging in non-alcoholic fatty liver disease: 

 Applications of magnetic resonance spectroscopy},

author = {Prarthana Thiagarajan and Stephen J Bawden and Guruprasad P Aithal},

year  = {2021},

date = {2021-02-01},

journal = {J. Clin. Med.},

volume = {10},

number = {4},

pages = {632},

publisher = {MDPI AG},

abstract = {Non-alcoholic fatty liver disease (NAFLD) is poised to dominate 

 the landscape of clinical hepatology in the 21st century. Its 

 complex, interdependent aetiologies, non-linear disease 

 progression and uncertain natural history have presented great 

 challenges to the development of effective therapies. Progress 

 will require an integrated approach to uncover molecular 

 mediators, key pathogenic milestones and response to 

 intervention at the metabolic level. The advent of precision 

 imaging has yielded unprecedented insights into these processes. 

 Quantitative imaging biomarkers such as magnetic resonance 

 imaging (MRI), spectroscopy (MRS) and elastography (MRE) present 

 robust, powerful tools with which to probe NAFLD metabolism and 

 fibrogenesis non-invasively, in real time. Specific advantages 

 of MRS include the ability to quantify static metabolite 

 concentrations as well as dynamic substrate flux in vivo. Thus, 

 a vast range of key metabolic events in the natural history of 

 NAFLD can be explored using MRS. Here, we provide an overview of 

 MRS for the clinician, as well as key pathways exploitable by 

 MRS in vivo. Development, optimisation and validation of 

 multinuclear MRS, in combination with other quantitative imaging 

 techniques, may ultimately provide a robust, non-invasive 

 alternative to liver biopsy for observational and longitudinal 

 studies. Through enabling deeper insight into inflammatory and 

 fibrogenic cascades, MRS may facilitate identification of novel 

 therapeutic targets and clinically meaningful endpoints in 

 NAFLD. Its widespread use in future could conceivably accelerate 

 study design, data acquisition and availability of 

 disease-modifying therapies at a population level.},

keywords = {magnetic resonance, metabolic liver disease, NAFLD, spectroscopy},

pubstate = {published},

tppubtype = {article}

}