ORCID Profile
0000-0002-0598-151X
Current Organisations
Fiona Stanley Hospital
,
University of Western Australia
,
Curtin University
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Publisher: Wiley
Date: 22-12-2010
Publisher: Wiley
Date: 18-12-2015
DOI: 10.1002/JMRI.24536
Abstract: To investigate the ability of texture analysis of MRI images to stage liver fibrosis. Current noninvasive approaches for detecting liver fibrosis have limitations and cannot yet routinely replace biopsy for diagnosing significant fibrosis. Forty-nine patients with a range of liver diseases and biopsy-confirmed fibrosis were enrolled in the study. For texture analysis all patients were scanned with a T2 -weighted, high-resolution, spin echo sequence and Haralick texture features applied. The area under the receiver operating characteristics curve (AUROC) was used to assess the diagnostic performance of the texture analysis. The best mean AUROC achieved for separating mild from severe fibrosis was 0.81. The inclusion of age, liver fat and liver R2 variables into the generalized linear model improved AUROC values for all comparisons, with the F0 versus F1-4 comparison the highest (0.91). Our results suggest that a combination of MRI measures, that include selected texture features from T2 -weighted images, may be a useful tool for excluding fibrosis in patients with liver disease. However, texture analysis of MRI performs only modestly when applied to the classification of patients in the mild and intermediate fibrosis stages.
Publisher: AMPCo
Date: 10-1995
Publisher: Wiley
Date: 11-2005
DOI: 10.1111/J.1445-5994.2005.00947.X
Abstract: Paracetamol is a component of a number of drugs taken in overdose (OD). The influence of alcohol use (acute or chronic) on the presentation and clinical course of paracetamol OD is contentious. This study explores the relationship between paracetamol OD, alcohol consumption and clinical outcomes at a regional Australian hospital. To determine the frequency, circumstances and outcomes of paracetamol OD presentations to a regional Australian general hospital over a 4-year period. Medical records of patients admitted to the Ballarat Health Services (BHS) as a result of paracetamol OD between January 2000 and December 2003 were reviewed. Patient demographics, amount of paracetamol ingested, other drug coingestions, alcohol history, previous medication OD, clinical course and outcomes were recorded. Annual admissions resulting from paracetamol OD almost doubled during the 4 years studied. The risk of a repeat paracetamol OD was highest within 4 weeks of the initial OD. Alcohol, benzodiazepines and antidepressants were commonly coingested. The strongest predictor of severe hepatotoxicity was delayed or no N-acetyl cysteine treatment in patients consuming greater than 10 g of paracetamol or with toxic serum paracetamol levels. A history of alcohol consumption did not appear to worsen outcomes.
Publisher: Massachusetts Medical Society
Date: 21-10-2021
Publisher: Springer Science and Business Media LLC
Date: 26-01-2010
DOI: 10.1007/S11894-009-0078-3
Abstract: Profound advances in our knowledge of hereditary hemochromatosis (HH) during the past 150 years have resulted in two distinct "iron ages": the pre-HFE gene era and the post-HFE gene era. During these periods, family studies, HLA association studies, and ultimately HFE gene studies in various populations informed us of the genotypic prevalence as well as the clinical and biochemical penetrance of HH. We learned that HH has a highly variable clinical penetrance in susceptible in iduals of Northern European ancestry. Further, we now recognize that the natural history of HH is not as discrete as previously believed, because genetic and environmental modifiers of disease penetrance are increasingly identified as influencing the clinical expression of HH.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2023
DOI: 10.1007/S12072-022-10469-7
Abstract: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value 0.007. EWAS identified dmCpGs related to three genes ( ANK1, MIR10a , PTPRN2 ) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced ( ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p 2.3 × 10 –3 ). We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.
Publisher: Wiley
Date: 21-08-2012
Publisher: Wiley
Date: 23-12-2015
DOI: 10.1111/JGH.12666
Abstract: Nonalcoholic fatty liver disease (NAFLD) and its metabolic risk factors are recognized during childhood and adolescence. Identification of adolescents at risk of NAFLD from childhood anthropometry may expose opportunities to influence the hepatic and metabolic destinies of in iduals. We sought associations between NAFLD diagnosed during adolescence and earlier life trajectories of anthropometry, in a population-based cohort of predominantly Caucasian adolescents. Assessment for NAFLD, using questionnaires and liver ultrasound, was performed on 1170 adolescents, aged 17 years, from the population-based Raine cohort. We sought associations between NAFLD in adolescents and serial anthropometric measurements recorded from birth, childhood, and adolescence. NAFLD was diagnosed in 15.2% of adolescents. Birth anthropometry, including birth weight, skinfold thickness, and ponderal index, was not associated with NAFLD. However, adiposity differences between 17-year-old adolescents with NAFLD and those without NAFLD were apparent from age 3 years. Greater adiposity trajectories for weight, body mass index, skinfold thickness, mid-arm circumference, and chest circumference from age 3 years onwards, particularly in males, were associated with the diagnosis of NAFLD and severity of hepatic steatosis at age 17 years (P < 0.05). The strength of the associations increased with age after 3 years for each adiposity measure (all P < 0.001). Trajectories of childhood adiposity are associated with NAFLD. Adiposity attained by 3 years of age and older, but not at birth, was associated with the diagnosis and severity of hepatic steatosis in late adolescence. Exploration of clinically relevant risk factors and preventative measures for NAFLD should begin during childhood.
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.CGH.2019.10.017
Abstract: Non-alcoholic fatty liver disease (NAFLD) is common and related to obesity and insulin resistance. Iron metabolism is impaired in obese in iduals and iron deficiency has been associated with physical inactivity. We investigated whether iron bioavailability is reduced in patients with NAFLD and contributes to reduced cardiorespiratory fitness. We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study-a longitudinal study of disease development in 2868 children in Western Australia. X Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI]). Iron bioavailability (assessed by mean corpuscular volume [MCV], mean corpuscular haemoglobin [MCH], transferrin saturation, and serum levels of iron) was inversely correlated with BMI in adolescents with NAFLD (P ≤ .01 for all, adjusted for sex) but not in adolescents without NAFLD (P > .30). MCV and MCH correlated with PWC (MCV, P = .002 for female and P = .0003 male participants MCH, P = .004 for female and P = .01 for male participants), irrespective of NAFLD status. Reduced PWC was associated with lower transferrin saturation in adolescents with NAFLD (reduction of 0.012 W/kg per unit decrease in transferrin saturation, P = .007) but not in adolescents without NAFLD (reduction of 0.001 W/kg, P = .40), adjusted for sex. This association was independent of MCV or MCH. In a well-defined cohort of adolescents, we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Xia & He Publishing
Date: 19-04-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2018
DOI: 10.1002/HEP.29347
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a complex chronic liver disorder. Examination of parental pregnancy‐related characteristics may provide insights into the origins of risk of NAFLD in offspring. We examined relationships between parental pregnancy‐related characteristics and NAFLD in 1,170 adolescent offspring aged 17 years participating in the Western Australian Pregnancy (Raine) Cohort Study. Fatty liver was diagnosed using liver ultrasound. NAFLD was diagnosed in 15.2% of adolescents at age 17 years. In univariate analysis, maternal factors associated with NAFLD in female offspring were younger maternal age ( P = 0.02), higher maternal prepregnancy BMI ( P 0.001), higher maternal weight gain by 18 weeks' gestation ( P 0.001), and maternal smoking during pregnancy ( P = 0.04). Paternal age or body mass index (BMI) were not associated with NAFLD in female offspring. In contrast, higher paternal BMI ( P 0.001), maternal prepregnancy BMI ( P 0.001), and lower family socioeconomic status (SES) at time of birth ( P = 0.001), but not parental age nor maternal gestational weight gain, were associated with NAFLD in male offspring. Using multivariate logistic regression, factors independently associated with NAFLD after adjusting for obesity in adolescent females included maternal obesity (odds ratio [OR], 3.46 95% confidence interval [CI], 1.49‐8.05 P = 0.004) and maternal weight gain ≥6.0 kg by the 18th week of gestation (OR, 1.10 95% CI, 1.04‐1.15 P 0.001). In adolescent males, family SES at the time of birth (OR, 9.07 95% CI, 1.54‐53.29 P = 0.02) remained significantly associated with NAFLD after multivariate modeling adjusted for adolescent obesity. Conclusion: Early‐life contributors to NAFLD show considerable sexual dimorphism. Maternal obesity and higher early‐mid gestational weight gain were associated with NAFLD in female offspring, whereas lower family SES at birth was associated with NAFLD in male offspring independent of adolescent obesity. (H epatology 2018 :108‐122).
Publisher: Wiley
Date: 04-2004
Publisher: Wiley
Date: 15-05-2014
DOI: 10.1111/JGH.12541
Abstract: Non-alcoholic fatty liver disease (NAFLD) and serum 25-hydroxyvitamin D (s25[OH]D) concentrations are both associated with adiposity and insulin resistance (IR) and thus may be pathogenically linked. We aimed to determine the prevalence of vitamin D deficiency in adolescents with NAFLD and to investigate the prospective and cross-sectional associations between s25[OH]D concentrations and NAFLD. Participants in the population-based West Australian Pregnancy (Raine) Cohort had seasonally adjusted s25(OH)D concentrations determined at ages 14 and then 17 years. NAFLD was diagnosed at 17 years using liver ultrasonography. Associations were examined after adjusting for potential confounders. Odds ratios (ORs) and confidence intervals (CIs) are reported per standard deviation in s25(OH)D concentrations. NAFLD was present in 16% (156/994) of adolescents. The majority of participants with NAFLD had either insufficient (51%) or deficient (17%) vitamin D status. s25(OH)D concentrations at 17 years were inversely associated with risk of NAFLD (OR 0.74, 95% CI 0.56, 0.97 P = 0.029), after adjusting for sex, race, physical activity, television/computer viewing, body mass index, and IR. The effect of s25(OH)D concentrations at 17 years was minimally affected after further adjusting for s25(OH)D concentrations at 14 years (OR 0.76, 95% CI 0.56, 1.03 P = 0.072). Lower s25(OH)D concentrations are significantly associated with NAFLD, independent of adiposity and IR. Screening for vitamin D deficiency in adolescents at risk of NAFLD is appropriate, and clinical trials investigating the effect of vitamin D supplementation in the prevention and treatment of NAFLD may be warranted.
Publisher: MDPI AG
Date: 18-11-2022
Abstract: Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood. The maternal serum phthalate measurements from the stored s les taken from Gen1 mothers at 18 and 34 weeks gestation were examined in relation to the cardiometabolic measures in 387 male offspring from the Raine Study. Data from the Gen2 follow-ups between 3 and 27 years were used. The primary outcomes were analysed longitudinally using linear mixed models for the repeated measures. Non-alcoholic fatty liver disease (NAFLD) was assessed at 17 years using logistic regression. A consistent positive relationship was observed between a prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) through adolescence into adulthood with systolic blood pressure. There were no other consistent cardiovascular associations. Mid-levels of prenatal exposures to Mono-n-butyl phthalate (MnBP) were associated with a greater incidence of NAFLD. Detectable Mono-3-carboxypropyl phthalate (MCPP) was associated with a lower serum HDL-C through late childhood into adulthood, while a higher prenatal exposure to mono-iso-butyl phthalate (MiBP), was associated with a higher LDL-C at 22 years of age. A mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites was associated with higher insulin in adulthood, while a higher prenatal exposure to the sum of the Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites was associated with higher fasting serum glucose in adulthood. In conclusion, our study demonstrated that higher prenatal phthalate exposures to some phthalate metabolites was associated with some adverse metabolic profiles through adolescence into adulthood, although the consistent themes were limited to a few metabolites and the outcomes of systolic blood pressure, fasting insulin and glucose.
Publisher: Wiley
Date: 09-2022
DOI: 10.1111/IMJ.15905
Publisher: Wiley
Date: 04-2022
DOI: 10.1111/IMJ.15732
Abstract: Low‐dose aspirin is commonly used for primary or secondary prophylaxis against cardiovascular disease in older people. However, the potential risk of upper gastrointestinal (UGI) ulceration and bleeding associated with low‐dose aspirin use is often not appreciated by prescribers and older consumers. Among 133 serial patients with UGI bleeding, aspirin‐users aged ≥70 years had a ninefold increased likelihood of overt UGI bleeding compared with non‐users, reducing by 90% in regular proton‐pump inhibitor users (adjusted odds ratio 0.10). We recommend risk‐versus‐benefit discussions when recommending aspirin to older people.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2022
DOI: 10.1007/S00394-022-02934-8
Abstract: Dietary fat intake has long been associated with fatty liver. Our study aimed to determine the effect of dietary fats on longitudinal fatty liver index (FLI) trajectories from adolescence to young adulthood. Nine hundred eighty-five participants in the Raine Study, Perth, Western Australia, Australia, had cross-sectional assessments at ages 14, 17, 20 and 22 years, during which anthropometric measurements and blood tests were obtained. FLI trajectories were derived from the longitudinal FLI results. Dietary fat intake was measured with a semi-quantitative food frequency questionnaire at 14 years and log multinominal regression analyses were used to estimate relative risks. Three FLI trajectories were identified and labelled as stable-low (79.1%, N = 782), low-to-high (13.9%, N = 132), and stable-high (7%, N = 71). The low-to-high group associated with an increased intake of the long-chain polyunsaturated fatty acids EPA, DPA and DHA (RR 1.27, 95% CI 1.10–1.48) relative to the stable-low group. Compared to the stable-low group, omega-6 and the ratio of omega-6 to omega-3 in the stable-high group were associated with an increased relative risk of 1.34 (95% CI 1.02–1.76) and 1.10 (95% CI 1.03–1.16), respectively. For those at high risk of fatty liver in early adolescence, high omega-6 fatty acid intake and a high ratio of omega-6 to omega-3 fatty acids are associated with increased risk of fatty liver. There should be caution in assuming these associations are causal due to possible undetected and underestimated confounding factors.
Publisher: The Endocrine Society
Date: 20-02-2019
Abstract: “Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA preserved across cell types) and extrinsic (EEAA dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development. In 995 participants (49.6% female age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors. Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.
Publisher: Wiley
Date: 07-2019
DOI: 10.1111/JGH.14699
Abstract: Bowel patterns are varied in the general population. Gastrointestinal symptoms are common reasons for clinical visits. We aimed to examine the usual bowel pattern and the prevalence and significance of gastrointestinal symptoms in a population-based cohort of Australian adolescents. Seventeen-year-old adolescents (n = 1279) in the Western Australian Pregnancy Cohort (Raine) Study participated in a cross-sectional assessment, involving health questionnaires. Questions included medical history, diet, bowel patterns, and gastrointestinal symptoms. Data were analyzed to identify patterns of bowel motions, gastrointestinal symptoms, and factors associated with these in adolescents. Multivariate logistic regression analysis was used to determine predictors of poorer self-rated health status. The dominant pattern of bowel motions was passage of stool that was "not too hard and not too soft" (Bristol stool types 3 and 4) in 90% and occurring between three and seven times per week in 74%. The most prevalent gastrointestinal symptoms included abdominal bloating (72%), abdominal pain (36%), nausea (25%), and constipation (20%). A "Western" dietary pattern was associated with abdominal bloating, constipation, and nausea (P < 0.05). Apart from diarrhea, gastrointestinal symptoms were more prevalent in female adolescents than male adolescents (P < 0.05 for all). Female sex (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.16-3.02, P = 0.01), nausea (OR 3.18, 95% CI 2.03-4.98, P < 0.001), and depression (OR 6.68, 95% CI 3.65-12.22, P = 0.03) were independently associated with poorer self-rated health status, after adjusting for other gastrointestinal symptoms. In adolescents, bowel patterns and gastrointestinal symptoms are erse and show sex differences. Nausea, depression, and female sex are significant factors for poorer self-rated health.
Publisher: Oxford University Press (OUP)
Date: 28-05-2022
Abstract: Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13–21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989–1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013–2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher’s exact and Mann–Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P & 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P & 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P & 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P & 0.001) and heart rate corrected augmentation index was lower in GUHS females (−8.4 vs −2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults. This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia. N/A.
Publisher: Wiley
Date: 28-04-2016
DOI: 10.1111/JGH.13241
Abstract: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) share risk associations of adiposity and insulin resistance. We examined the impact of a PCOS diagnosis on the metabolic phenotype of adolescent girls with NAFLD and compared this to girls without PCOS or NAFLD and to age-matched boys. Community-based adolescents from the Raine Cohort participated in assessments for NAFLD (572 girls and 592 boys) and PCOS (244 girls). One hundred and ninety-nine girls attended both assessments. Amongst the 199 girls, PCOS was diagnosed in 16.1% and NAFLD in 18.6%. NAFLD was diagnosed in 10.1% of the boys. NAFLD was more prevalent in girls with PCOS than girls without PCOS (37.5% vs 15.1%, P = 0.003). Girls with NAFLD plus PCOS had greater adiposity (waist circumference, body mass index, suprailiac skinfold thickness [SST], serum androgens, high-sensitivity C-reactive protein, ferritin, homeostasis model assessment for insulin resistance (HOMA-IR), and lower serum sex hormone binding globulin levels than girls with NAFLD without a PCOS diagnosis (all P < 0.05). Girls with NAFLD plus PCOS had similar adiposity, HOMA-IR, and adiponectin levels to boys with NAFLD, but more adiposity, serum leptin and HOMA-IR than both girls and boys without NAFLD. PCOS (odds ratios 2.99, 95% confidence intervals 1.01-8.82, P = 0.048) and SST (odds ratios 1.14, 95% confidence intervals 1.08-1.20, P < 0.001) independently predicted NAFLD in adolescent girls, however, serum androgens and HOMA-IR levels did not. Adolescent girls with NAFLD plus PCOS have a similar metabolic phenotype to boys with NAFLD. Increasing SST and pre-existing PCOS independently predict NAFLD in adolescent girls.
Publisher: Wiley
Date: 05-12-2023
DOI: 10.1111/APT.17270
Abstract: This article is linked to Attia et al paper. To view this article, visit 0.1111/apt.17233
Publisher: Elsevier BV
Date: 2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
DOI: 10.1038/AJG.2013.95
Abstract: Poor dietary habits have been implicated in the development of nonalcoholic fatty liver disease (NAFLD) however, little is known about the role of specific dietary patterns in the development of NAFLD. We examined prospective associations between dietary patterns and NAFLD in a population-based cohort of adolescents. Participants in the Western Australian Pregnancy Cohort (Raine) Study completed a food frequency questionnaire at 14 years and had liver ultrasound at 17 years (n=995). Healthy and Western dietary patterns were identified using factor analysis and all participants received a z-score for these patterns. Prospective associations between the dietary pattern scores and risk of NAFLD were analyzed using multiple logistic regression. NAFLD was present in 15.2% of adolescents. A higher Western dietary pattern score at 14 years was associated with a greater risk of NAFLD at 17 years (odds ratio (OR) 1.59 95% confidence interval (CI) 1.17-2.14 P<0.005), although these associations were no longer significant after adjusting for body mass index at 14 years. However, a healthy dietary pattern at 14 years appeared protective against NAFLD at 17 years in centrally obese adolescents (OR 0.63 95% CI 0.41-0.96 P=0.033), whereas a Western dietary pattern was associated with an increased risk of NAFLD. A Western dietary pattern at 14 years in a general population s le was associated with an increased risk of NAFLD at 17 years, particularly in obese adolescents. In centrally obese adolescents with NAFLD, a healthy dietary pattern may be protective, whereas a Western dietary pattern may increase the risk.
Publisher: Elsevier BV
Date: 2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
DOI: 10.1002/HEP.21957
Publisher: Cambridge University Press (CUP)
Date: 21-09-2020
DOI: 10.1017/S2040174420000884
Abstract: Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Publisher: Elsevier BV
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 16-03-2022
DOI: 10.1111/IMJ.15125
Abstract: Up to 3% of methotrexate (MTX)-treated rheumatoid arthritis (RA) patients might develop liver fibrosis or cirrhosis, requiring effective screening algorithms. To assess the utility of non-invasive liver fibrosis assessment in RA patients on MTX. Fifty-six patients were recruited from rheumatology outpatient clinics in a public tertiary centre from July 2017 to October 2018. Clinical data was collected. Screening for hepatic fibrosis was performed using transient elastography (TE), aminoaspartate transaminase to platelet ratio index (APRI), Hepascore and Fibrosis-4 index (FIB-4). Those with suspected significant liver fibrosis based on these screening tests were assessed by a hepatologist. Twenty-seven patients were suspected to have liver fibrosis on screening, including 10/56 (18%) by TE, 20/56 (36%) by Hepascore, 2/56 by APRI (4%) and 1/56 by FIB-4 (2%). Of these 27 patients, 11 were reviewed by a hepatologist and one diagnosed with significant liver fibrosis. TE, but not APRI, Hepascore or FIB-4, was found to have 100% sensitivity and 84% specificity (P = 0.029) for hepatologist-diagnosed liver fibrosis. Liver fibrosis develops in a minority of MTX-treated RA patients. The present study suggests that TE is a more sensitive screening test than APRI, FIB-4 or Hepascore in the identification of people with RA at risk of hepatic fibrosis.
Publisher: Oxford University Press (OUP)
Date: 08-2000
Abstract: The toxic effects of paracetamol in overdose quantities are well recognised but the occurrence of anaphylactoid reactions to paracetamol is infrequently identified by consumers and health care professionals. Nevertheless adverse reactions to this drug, even in therapeutic doses, can have fatal or near fatal consequences. A case of an anaphylactoid reaction to paracetamol is described.
Publisher: Wiley
Date: 10-03-2022
DOI: 10.1111/IMJ.15603
Abstract: Early and accurate non‐invasive diagnosis of liver fibrosis is important for reducing the burden of cirrhosis and related complications. This cross‐sectional study compares shear wave elastography (SWE), transient elastography (TE) and clinical markers of chronic liver disease in patients with various liver disorders. Liver ultrasound with SWE was performed on 421 adult patients, 227 of whom also had TE. Patient age, gender, body mass index (BMI), liver disease aetiology and laboratory results were recorded. Associations between SWE, TE and other tests for liver fibrosis and chronic liver disease severity were sought. Advanced liver fibrosis was defined as liver stiffness measurement (LSM) equivalent to ≥F3 using Metavir staging. Patients were predominantly male (68%), with mean (standard deviation) age 54 (13) years, BMI 28 (6) kg/m 2 and serum alanine aminotransferase (ALT) 39 (27) U/L. Liver disorders were predominantly non‐alcoholic fatty liver disease (NAFLD), chronic hepatitis B (CHB), chronic hepatitis C (CHC) and alcohol‐related liver disease. The median (interquartile range) LSM was 10 (6–20) kPa with SWE and 9.2 (6–21) kPa with TE. Advanced liver fibrosis was associated with older age, higher BMI, model for end‐stage liver disease score, aspartate aminotransferase (AST), AST/ALT ratio, AST to platelet ratio index, fibrosis‐4 index and Hepascore. SWE and TE LSM were positively correlated, particularly for NAFLD and CHC. SWE LSM predicted ultrasound and endoscopy‐diagnosed portal hypertension and oesophageal varices. Across various liver diseases, SWE is at least comparable with TE and other non‐invasive tests of liver fibrosis. SWE is accurate for predicting liver‐related portal hypertension.
Publisher: Research Square Platform LLC
Date: 06-10-2022
DOI: 10.21203/RS.3.RS-2114814/V1
Abstract: BACKGROUND AND AIMS : Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH & RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially-methylated CpG sites (dmCpGs) for which ≥2 probes per gene remained significant across four statistical models with a nominal p-value .007. EWAS identified dmCpGs related to three genes ( ANK1, MIR10a , PTPRN2 ) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced ( ANK1 n =6, MIR10a n =7, PTPRN2 n =3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p .3 x 10 -3 ). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.
Publisher: Springer Science and Business Media LLC
Date: 27-12-2019
DOI: 10.1038/S41598-019-56732-0
Abstract: Development of advanced hepatic fibrosis in HFE Hemochromatosis (HH) is influenced by hepatic iron concentration (HIC) and age. In patients with HH, it is important to assess the likelihood of cirrhosis and thus the need for confirmatory liver biopsy. Therapeutic phlebotomy also provides an estimate of mobilisable iron stores. We determined whether mobilisable iron stores may predict the presence of advanced fibrosis. Retrospective analysis of 137 male and 65 female HH subjects was undertaken. Biochemical, histological and phlebotomy data were available on all subjects. The mean values of HIC, HIC × [age], mobilisable iron, mobilisable iron × [age] and serum ferritin in the cohort were higher in the group with advanced fibrosis. HIC had an optimum sensitivity and specificity of 73% for the diagnosis of advanced liver fibrosis, with a cut-off HIC level of 200 µmol/g (AUROC 0.83, p 0.0001). AUROC for HIC was greater in females (0.93) than males (0.79). Mobilisable iron had an optimum sensitivity and specificity both of 83% at a cut-off of 9.6 g for the prediction of advanced fibrosis in all subjects (AUROC 0.92, p 0.0001). Mobilisable iron stores provide a simple, clinically useful indication of the risk of advanced fibrosis and should routinely be considered.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-08-2013
DOI: 10.1002/HEP.26495
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is regarded as the hepatic manifestation of the metabolic syndrome. In adults, NAFLD is a determinant of arterial stiffness and cardiovascular risk, independent of the metabolic syndrome. Our aim was to ascertain if NAFLD is associated with arterial stiffness, independent of cardiometabolic factors in a population-based cohort of adolescents. The 17-year-olds (n = 964) from an Australian birth cohort had measures of anthropometry, blood pressure, fasting insulin, glucose, lipids, and NAFLD by ultrasound. Two-step cluster analysis identified youth at high metabolic risk. Measures of arterial stiffness (pulse wave velocity [PWV] and augmentation index corrected for heart rate [AI@75]) were obtained using applanation tonometry. The overall prevalence of NAFLD was 13.3%. The "high risk" metabolic cluster at age 17 years included 16% males and 19% females. Compared to "low risk," the "high risk" cluster participants had greater waist circumference, triglycerides, insulin, systolic blood pressure, and lower high-density lipoprotein (HDL) cholesterol (all P < 0.0001). Those who had NAFLD but were not in the "high risk" metabolic cluster did not have increased PWV or AI@75. However, males and females who had NAFLD in the presence of the metabolic cluster had greater PWV (b = 0.20, 95% confidence interval [CI] 0.01 to 0.38, P = 0.037). Males who had NAFLD in the presence of the metabolic cluster had greater AI@75 (b = 6.3, 95% CI 1.9 to 10.7, P = 0.005). NAFLD is only associated with increased arterial stiffness in the presence of the "high risk" metabolic cluster. This suggests that arterial stiffness related to the presence of NAFLD is predicated on the presence of an adverse metabolic profile in adolescents.
Publisher: Wiley
Date: 13-04-2021
DOI: 10.1111/JGH.15511
Publisher: Public Library of Science (PLoS)
Date: 08-08-2016
Publisher: Cambridge University Press (CUP)
Date: 07-12-2020
DOI: 10.1017/S2040174420001166
Abstract: Globally, the availability and formulations for the administration of cannabis are changing with decriminalization or legalization of recreational use in some jurisdictions, and the prescription of cannabis also occurring. These changes are likely to affect the prevalence of use, including by women of childbearing age. The effects of in utero and infant alcohol and tobacco exposure are well-documented, but the outcomes of cannabis exposure are less certain. The content of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis has progressively increased over several decades. This review explores the limited knowledge surrounding the epidemiology of gestational and postnatal cannabis exposure and implications for the mother–placenta–fetus/neonate triad. We examine cannabis’ effects from antenatal and lactation exposure on (a) pregnancy and perinatal outcomes, (b) placental health, and (c) longer term cardiometabolic and neurodevelopmental risks and outcomes. Though definitive outcomes are lacking, gestational cannabis has been associated with increased risk of other substance use during pregnancy impaired placental blood flow increased risk of small for gestational age births and associated complications. Childhood and adolescent outcomes are sparsely assessed, with suggested outcomes including increased risk of depression and attention-deficit hyperactivity disorder. Cardiometabolic implications of gestational cannabis use may include maternal fatty liver, obesity, insulin resistance, and increased risk of gestational diabetes mellitus (GDM), with potential consequences for the fetus. Clinical implications for pediatric practice were explored in a bid to understand any potential risk or impact on child health and development.
Publisher: Elsevier BV
Date: 06-2021
Publisher: AMPCo
Date: 05-2001
Publisher: Wiley
Date: 24-04-2022
Abstract: Hepatic steatosis duration and severity are risk factors for liver fibrosis and cardiometabolic disease. We assessed the diagnostic accuracy of attenuation imaging (ATI), compared with histologic hepatosteatosis grading in adults with varied suspected liver pathologies. Liver biopsy was performed on 76 patients (51 women, 25 men) with non‐malignant diffuse parenchymal liver disease, within 4 weeks of multiparametric liver ultrasound including attenuation imaging (ATI). Skin‐liver capsule distance (SCD) and body mass index (BMI) were measured. Histologic steatosis was graded none (S0), mild (S1), moderate (S2) or severe (S3). We compared histology and sonographic parameters. The median patient age was 50.5 (range 18–83) years and BMI 28.9 kg/m 2 (interquartile range 24.0–33.3). The distribution of histologic steatosis grade was S0 (44%), S1(17%), S2(30%) and S3(9%). Median ATI value for each biopsy steatosis grade was 0.60 (IQR: 0.52–0.65), 0.65 (IQR: 0.6–0.71), 0.83 (IQR: 0.74–0.90) and 0.90 (IQR: 0.82–1.01) dB/cm/MHz for S0, S1, S2 and S3, respectively. The AUC of ATI for detection of any steatosis (S1‐S3) and moderate to severe steatosis (S2‐S3) was 0.85 (95% CI: 0.75–0.91) and 0.91 (95% CI: 0.83–0.99) with cut‐offs of 0.55 and 0.62 dB/cm/MHz. ATI threshold of 0.74 dB/cm/MHz was able to discriminate between S0‐S1 and S2‐3 with accuracy, CI and kappa statistic of 0.8889, 0.65–0.98 and 0.7534. We found a good correlation between ATI and steatosis grade. The most accurate discrimination was between none to mild (S0‐1) and moderate to severe (S2‐3) steatosis.
Publisher: Elsevier BV
Date: 06-2021
DOI: 10.1016/J.DLD.2020.11.037
Abstract: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in young populations. However, there are inadequate data regarding diagnosis of NAFLD. We aimed to validate three scoring systems against a previous standard of suprailiac skinfold thickness for diagnosing NAFLD in population-based adolescents. Seventeen-year-old adolescents (n = 899), participating in the Raine Study, attended a cross-sectional follow-up. NAFLD was diagnosed using liver ultrasound. Scores for Fatty liver index (FLI), Hepatic Steatosis Index (HSI) and Zhejiang University index (ZJU index) were calculated. Diagnostic accuracy of these diagnostic tests was evaluated through discrimination and calibration. NAFLD was diagnosed 9% in males and 15% in females. The three scoring systems demonstrated better discrimination performance for NAFLD in males (AUC was FLI:0.82, HSI: 0.83 and ZJU index: 0.83) compared to females (AUC was FLI: 0.67, HSI: 0.67 and ZJU index: 0.67). Suprailiac skinfold performed better than the scoring systems (overall AUC: 0.82 male AUC:0.88 female AUC:0.73). FLI had best calibration performance. Suprailiac skinfold thickness was a better predictor of ultrasound-diagnosed NAFLD than the three diagnostic scoring systems investigated. The higher performance characteristics of the algorithmic scoring systems in males compared with females may have implications for use in population assessments.
Publisher: AMPCo
Date: 11-2000
Publisher: Wiley
Date: 31-12-2016
DOI: 10.1111/TRF.13446
Abstract: Blood products are commonly transfused for patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). While concerns exist about further bleeding and mortality in subsets of patients receiving red blood cell (RBC) transfusion, the impact of non-RBC blood products has not previously been systematically investigated. The aim of the study was to investigate the associations between blood products transfusion, further bleeding, and mortality after acute NVUGIB. A retrospective cohort study examined further bleeding and 30-day and 1-year mortality in adult patients who underwent gastroscopy for suspected acute NVUGIB between 2008 and 2010 in three tertiary hospitals in Western Australia. Survival analysis was performed. A total of 2228 adults (63% male) with 2360 hospital admissions for NVUGIB met the inclusion criteria. Median age at presentation was 70 years (range, 19-99 years). Thirty-day mortality was 4.9% and 1-year mortality was 13.9%. Transfusion of 4 or more units of RBCs was associated with greater than 10 times the odds of further bleeding in patients with a hemoglobin level of more than 90 g/L (odds ratio, 11.9 95% confidence interval [CI], 3.1-45.7 p ≤ 0.001), but was not associated with mortality. Administration of 5 or more units of fresh-frozen plasma (FFP) was associated with increased 30-day (hazard ratio, 2.8 95% CI, 1.3-5.9 p = 0.008) and 1-year (hazard ratio, 2.6 95% CI, 1.3-5.0 p = 0.005) mortality after adjusting for coagulopathy, comorbidity, Rockall score, and other covariates. In this large, multicenter study of NVUGIB, RBC transfusion was associated with further bleeding but not mortality, while FFP transfusion was associated with increased mortality in a subset of patients.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 18-07-2023
DOI: 10.1111/AJO.13589
Abstract: Cannabis is one of the most common non-prescribed psychoactive substances used in pregnancy. The prevalence of gestational cannabis use is increasing. The aim was to examine the prevalence of gestational cannabis use and associated pregnancy and neonate outcomes. A retrospective observational study involving pregnant women delivering in 2019 was conducted at a tertiary hospital in Perth, Western Australia. Gestational cannabis and other substance use records were based on maternal self-report. Pregnancy outcomes included neonatal gestational age, birthweight, birth length, head circumference, resuscitation measures, special care nursery admission, 5-min Apgar score and initial neonatal feeding method. Among 3104 pregnant women (mean age: 31 years), gestational cannabis use was reported by 1.6% (n = 50). Cannabis users were younger, more likely to use other substances and experience mental illness or domestic violence compared with non-users. Neonates born to cannabis users had a lower mean gestational age, birthweight and birth length compared to those born to non-cannabis users. Gestational cannabis use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6-6.7) and tobacco smoking (OR 2.2, 95% CI 1.5-3.6) were associated with increased odds of a low-birthweight neonate. Combined cannabis and tobacco use during pregnancy further increased the likelihood of low birthweight (LBW, adjusted OR 3.9, 95% CI 1.6-9.3). Multivariate logistic regression analysis adjusted for maternal sociodemographical characteristics, mental illness, alcohol, tobacco and other substance use demonstrated gestational cannabis use to be independently associated with LBW (OR 2.3, 95% CI 1.1-5.2). Gestational cannabis use was independently associated with low birthweight, synergistically affected by tobacco smoking.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
DOI: 10.1002/HEP.24097
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a predominantly adult-diagnosed disorder. Knowledge regarding the epidemiology, phenotype, and metabolic risk factors, during adolescence is limited. We sought to determine the prevalence, phenotype, and predictors of NAFLD in 1170 community-based adolescents in the Western Australian Pregnancy Cohort (Raine) Study (the Raine Cohort) who underwent a cross-sectional assessment that included questionnaires, anthropometry, cardiovascular examinations, blood tests, and abdominal ultrasound examinations. Among the 1170 adolescents assessed, the prevalence of NAFLD was 12.8%. Females compared with males had a significantly higher prevalence of NAFLD (16.3% versus 10.1%, P = 0.004) and central obesity (33.2% versus 9.9%, P < 0.05). The severity of hepatic steatosis was associated with the body mass index, waist circumference, subcutaneous adipose tissue thickness (SAT), serum leptin level, homeostasis model assessment for insulin resistance score (P < 0.001 for all), and serum alanine aminotransferase level (P < 0.005) in both genders, but it was associated with increasing visceral adipose tissue thickness (VAT P < 0.001) and decreasing serum adiponectin levels (P 0.05) however, in comparison with females with NAFLD, males with NAFLD had greater VAT, a more severe metabolic phenotype with higher glucose levels and systolic blood pressure and lower adiponectin and high-density lipoprotein cholesterol levels (P < 0.001 for all), and greater measures of liver injury (alanine aminotransferase and aspartate aminotransferase, P < 0.001 for all). Similarly, metabolic syndrome was more common in males than females with NAFLD (24% versus 8%, P = 0.01). Suprailiac skinfold thickness predicted NAFLD independently of the body mass index, insulin resistance, and VAT. Gender differences in adolescent NAFLD are related to differences in adipose distribution and adipocytokines. The male phenotype of NAFLD is associated with more adverse metabolic features and greater visceral adiposity than the female phenotype despite the lower prevalence of NAFLD.
Publisher: Wiley
Date: 28-01-2022
DOI: 10.1111/APT.16750
Abstract: This article is linked to Lazarus et al papers. To view these articles, visit 0.1111/apt.16720 and 0.1111/apt.16768
Publisher: Public Library of Science (PLoS)
Date: 21-03-2013
Publisher: Informa UK Limited
Date: 05-2009
DOI: 10.1586/EEM.09.9
Abstract: Hereditary hemochromatosis due to homozygosity for the C282Y mutation in the HFE gene product is the most common autosomal recessive genetic disorder in populations of northern European descent, where it attains a maximum prevalence of approximately one in 200. Cross-sectional and longitudinal studies have revealed that clinically significant iron-overload disease develops in at least 28% of male and 1% of female HFE C282Y homozygotes. The relatively low clinical penetrance is largely unexplained. Current evidence suggests a limited role for digenic inheritance of mutations in iron homeostasis genes in modifying the penetrance of hemochromatosis. Male gender is a strong genetic factor, promoting expression of clinical disease. Dietary intake of alcohol and noncitrus fruit may also act as important environmental modifiers of penetrance. With genetic analyses becoming simpler to perform, new genetic modifiers of hepatic iron loading and liver fibrogenesis are likely to be forthcoming.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2013
DOI: 10.1002/HEP.26184
Abstract: Genetic factors account for a significant proportion of the phenotypic variance of nonalcoholic fatty liver disease (NAFLD) however, very few predisposing genes have been identified. We aimed to (1) identify novel genetic associations with NAFLD by performing a genome-wide association study (GWAS), and (2) examine the biological expression of the strongest genetic associations in a separate cohort. We performed GWAS of a population-based cohort (Raine Study) of 928 adolescents assessed for NAFLD by ultrasound at age 17. Expression of genes with single nucleotide polymorphisms (SNPs) that were associated with NAFLD at a significance level of P < 10(-5) was examined in adults with NAFLD and controls by quantifying hepatic messenger RNA (mRNA) expression and serum levels of protein. After adjustment for sex and degree of adiposity, SNPs in two genes expressed in liver were associated with NAFLD adolescents: group-specific component (GC) (odds ratio [OR], 2.54 P = 1.20 × 10(-6)) and lymphocyte cytosolic protein-1 (LCP1) (OR, 3.29 P = 2.96 × 10(-6)). SNPs in two genes expressed in neurons were also associated with NAFLD: lipid phosphate phosphatase-related protein type 4 (LPPR4) (OR, 2.30 P = 4.82 × 10(-6)) and solute carrier family 38 member 8 (SLC38A8) (OR, 3.14 P = 1.86 × 10(-6) ). Hepatic GC mRNA was significantly reduced (by 83%) and LCP1 mRNA was increased (by 300%) in liver biopsy s les from patients with NAFLD compared to controls (P < 0.05). Mean serum levels of GC protein were significantly lower in patients with NAFLD than controls (250 ± 90 versus 298 ± 90, respectively P = 0.004) GC protein levels decreased with increasing severity of hepatic steatosis (P < 0.01). The association between GC and LCP1 SNPs and NAFLD as well as altered biological expression implicate these genes in the pathogenesis of NAFLD.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JHEP.2017.03.029
Abstract: The pathway to non-alcoholic fatty liver disease (NAFLD) in adolescents may have its origins in adiposity gains, nutrition and sedentary lifestyle established during childhood. There is inadequate knowledge regarding the associations between infant nutrition and subsequent NAFLD. We examined the association of maternal factors and infant nutrition, with the subsequent diagnosis of NAFLD in adolescents. Adolescents aged 17years in the Western Australian Pregnancy (Raine) Cohort study had fatty liver assessment using liver ultrasound. Prospectively recorded data on maternal pregnancy and infant feeding were examined against a NAFLD outcome during late adolescence. NAFLD was diagnosed in 15.2% of the 1,170 adolescents examined. Ninety-four percent had been breastfed as infants. The duration of breastfeeding before starting supplementary milk was ⩾4months in 54.4% and ⩾6months in 40.6%. Breastfeeding without supplementary milk ⩾6months (adjusted odds ratio [OR]: 0.64 95% confidence interval [CI]: 0.43-0.94, p=0.02), maternal pre-pregnancy obesity (adjusted OR: 2.29 95% CI: 1.21-4.32, p=0.01) and adolescent obesity (adjusted OR: 9.08 95% CI: 6.26-13.17, p<0.001) were associated with NAFLD independent of a Western dietary pattern at 17years of age. Adolescents with NAFLD who had been breastfed for ⩾6months had a less adverse metabolic profile compared with adolescents breastfed for <6months. Supplementary milk intake starting before 6months was associated with a higher prevalence and ultrasound severity of NAFLD compared with intake starting after 6months (17.7% vs. 11.2%, p=0.003 and 7.8% vs. 3.4%, p=0.005 respectively). Though NAFLD is generally mediated through adiposity gains, breastfeeding for at least 6months, avoidance of early supplementary formula milk feeding, and normal maternal pre-pregnancy BMI may reduce the odds of a NAFLD diagnosis during adolescence. Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder in which there is too much fat in the liver of people who do not consume excessive amounts of alcohol. In this large study, we found that infants who consumed breast milk for less than 6months before starting infant formula milk, infants who were obese as teenagers or had mothers who were obese at the start of pregnancy, were much more likely to have NAFLD at 17years of age. Based on our findings we consider that reducing the risk of NAFLD in teenagers needs to start before birth, by encouraging normal body mass index before pregnancy, as well as breastfeeding without infant formula milk consumption for the first 6months of life.
Publisher: Springer Science and Business Media LLC
Date: 04-06-2022
DOI: 10.1007/S00384-022-04191-X
Abstract: Colorectal cancer (CRC) is increasingly diagnosed in in iduals aged 50 years, resulting in advocacy of screening from age 45 years. Despite existing knowledge associating CRC with conventional adenomas, the significance of sessile serrated lesions (SSLs) on the burden of CRC is less detailed. We aimed to provide contemporary estimates for SSL prevalence and examine patient and procedure factors associated with SSL detection. Retrospective observational study examining associations between SSL and conventional adenoma detection, polyp histopathology, patient, and procedure characteristics in an outpatient colonoscopy unit over 12 months. From 2097 colonoscopies, SSL detection was 13.8% overall and 12.5% in patients 50 years. SSLs were mostly proximal in location (64%), and SSL detection was significantly higher in females compared with males (16.2% vs. 11.7%, p = 0.003), particularly in those 50 years (16.8% vs. 8.6%, p 0.001). In multivariable analysis, SSL detection was associated with female sex (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.15–1.91), synchronous conventional adenoma detection (aOR 1.36, 95% CI 1.04–1.78) and BMI ≥ 25 kg/m 2 (aOR 1.34, 95% CI 1.02–1.77). Conventional adenoma detection was 33.6% and associated with age ≥ 50 years (aOR 3.57, 95% CI 2.84–4.47) and synchronous SSL detection (aOR 1.36, 95% CI 1.03–1.79). We observed age and sex disparities in polyp types and prevalence in this outpatient colonoscopy population. SSLs were most prevalent in females aged 50 years, suggesting a potential increased susceptibility of young females to SSLs and CRC. Our findings may have implications for the design of CRC screening programs.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2020
DOI: 10.1038/S41598-020-58543-0
Abstract: Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions.
No related grants have been discovered for OYEKOYA AYONRINDE.