Publications

@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{Newsome2020-vk,

title = {Volixibat in adults with non-alcoholic steatohepatitis: 24-week 

 interim analysis from a randomized, phase II study},

author = {Philip N Newsome and Melissa Palmer and Bradley Freilich and Muhammad Y Sheikh and Aasim Sheikh and Harry Sarles and Robert Herring and Parvez Mantry and Zeid Kayali and Tarek Hassanein and Hak-Myung Lee and Guruprasad P Aithal and Volixibat group},

year  = {2020},

date = {2020-08-01},

journal = {J. Hepatol.},

volume = {73},

number = {2},

pages = {231\textendash240},

publisher = {Elsevier BV},

abstract = {BACKGROUND \& AIMS: Volixibat is an inhibitor of the apical 

 sodium-dependent bile acid transporter (ASBT) that has been 

 hypothesized to improve non-alcoholic steatohepatitis (NASH) by 

 blocking bile acid reuptake and stimulating hepatic bile acid 

 production. We studied the safety, tolerability and efficacy of 

 volixibat in patients with NASH. METHODS: In this double-blind, 

 phase II dose-finding study, adults with $geq$5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive 

 volixibat (5, 10 or 20 mg) or placebo once daily for 48 weeks. The endpoints of a predefined interim analysis (n = 80), at week 

 24, were: $geq$5% reduction in MRI-proton density fat fraction 

 and $geq$20% reduction in serum alanine aminotransferase 

 levels. The primary endpoint was a $geq$2-point reduction in 

 non-alcoholic fatty liver disease activity score without 

 worsening fibrosis at week 48. RESULTS: Volixibat did not meet 

 either interim endpoint; the study was terminated owing to lack 

 of efficacy. In participants receiving any volixibat dose, mean 

 serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile 

 acid synthesis) increased from baseline to week 24 (+38.5 ng/ml 

 [SD 53.18]), with concomitant decreases in serum total 

 cholesterol (-14.5 mg/dl [SD 28.32]) and low-density lipoprotein 

 cholesterol (-16.1 mg/dl [SD 25.31]). These changes were 

 generally dose-dependent. On histological analysis, a greater proportion of participants receiving placebo (38.5},

keywords = {Alanine aminotransferase, ASBT inhibitor, Humans, Non-alcoholic   fatty liver disease, Non-alcoholic steatohepatitis, Phase II, Steatosis},

pubstate = {published},

tppubtype = {article}

}