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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. [ABSTRACT FROM AUTHOR]

Background: Early and accurate non‐invasive diagnosis of liver fibrosis is important for reducing the burden of cirrhosis and related complications. Aim: 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. Methods: 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. Results: Patients were predominantly male (68%), with mean (standard deviation) age 54 (13) years, BMI 28 (6) kg/m2 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The article talks about Non-variceal upper gastrointestinal bleeding (UGIB) resulting from gastro duodenal ulcer haemorrhage, which is a common cause of hospitalisation in middle-aged and older Australians. Mentions aspirin is the most common antiplatelet agent used at low dose for the prevention of cardiovascular events; however, low-dose enteric-coated aspirin has not fulfilled the expectation of reducing gastroduodenal ulceration and bleeding.

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. [ABSTRACT FROM AUTHOR]

Background and Aim: 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. Methods: 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. Results: 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. Conclusions: In adolescents, bowel patterns and gastrointestinal symptoms are diverse and show sex differences. Nausea, depression, and female sex are significant factors for poorer self‐rated health. [ABSTRACT FROM AUTHOR]

Background & Aims 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. Methods Adolescents aged 17 years 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. Results 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 ⩾4 months in 54.4% and ⩾6 months in 40.6%. Breastfeeding without supplementary milk ⩾6 months (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 17 years of age. Adolescents with NAFLD who had been breastfed for ⩾6 months had a less adverse metabolic profile compared with adolescents breastfed for <6 months. Supplementary milk intake starting before 6 months was associated with a higher prevalence and ultrasound severity of NAFLD compared with intake starting after 6 months (17.7% vs. 11.2%, p = 0.003 and 7.8% vs. 3.4%, p = 0.005 respectively). Conclusion Though NAFLD is generally mediated through adiposity gains, breastfeeding for at least 6 months, avoidance of early supplementary formula milk feeding, and normal maternal pre-pregnancy BMI may reduce the odds of a NAFLD diagnosis during adolescence. Lay summary 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 6 months 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 17 years 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 6 months of life. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lazarus et al papers. To view these articles, visit https://doi.org/10.1111/apt.16720 and https://doi.org/10.1111/apt.16768 [ABSTRACT FROM AUTHOR]

Background and Aims: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background and Aim 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 individuals. We sought associations between NAFLD diagnosed during adolescence and earlier life trajectories of anthropometry, in a population-based cohort of predominantly Caucasian adolescents. Methods 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. Results 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). Conclusions 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. [ABSTRACT FROM AUTHOR]

Hereditary hemochromatosis (HH) comprises a group of inherited disorders of iron metabolism that can result in progressive iron overload, morbidity, and mortality, generally in adulthood. HFE-related HH is the most common type of HH and will form the core of this discussion. The discovery of new proteins and gene mutations has defined other types of HH, termed non-HFE HH. The regulatory protein hepcidin has a central role in iron homeostasis in these disorders. While the liver is the predominant organ of iron deposition and iron-overload-related disease in HFE-related HH, involvement of extrahepatic tissue can also result in morbidity and mortality if the disorder is not diagnosed before organ damage develops. This review traverses the road from HFE genotype to phenotype with a focus on clinical penetrance, modifier factors for disease expression, and current thoughts and controversies on HH diagnosis and screening. [ABSTRACT FROM AUTHOR]

Background: Up to 3% of methotrexate (MTX)‐treated rheumatoid arthritis (RA) patients might develop liver fibrosis or cirrhosis, requiring effective screening algorithms. Aims: To assess the utility of non‐invasive liver fibrosis assessment in RA patients on MTX. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Shear wave elastography (SWE) is an emerging ultrasound-related technology for assessment of liver fibrosis. The usefulness and reliability of SWE is unclear relative to other markers of liver fibrosis. We compared the clinical usefulness of SWE relative to transient elastography (TE), liver ultrasound and other standard biochemical markers of chronic liver disease in patients with varied liver disorders. SWE assessment was performed using a Toshiba Aplio 500 or Canon Aplio i800 machine, concurrently with liver ultrasound on 421 adult patients. Amongst these patients 227 also had liver transient elastography (TE). Patient age, gender, body mass index (BMI), alcohol history, liver disease diagnosis, and laboratory results were recorded. Associations between SWE, TE and patient factors were sought. Suspected significant liver fibrosis was defined by liver stiffness measurement interpretation of ≥ F2 equivalent using Metavir staging. Patients were predominantly male (67.5%). Males and females were matched as regards age and BMI. The indications for SWE included nonalcoholic fatty liver disease (10%), chronic hepatitis B (22%), chronic hepatitis C (38%), alcohol-related liver disease (18%) and others (12%). 23%The mean (standard deviation) age was 53 (14) years, body mass index 27.7 (6.3) kg/m2, ultrasound-measured skin to liver capsule distance 20.0 (7.3)mm, serum ALT 39(27) U/L and AST 48(32) U/L. The median (IQR) liver stiffness was 9.9 (6.4-20.0) kPa with SWE and 9.2 (5.8-20.9) kPa with TE. Patients with suspected significant liver fibrosis determined by SWE, compared with patients not suspected of having significant fibrosis, were significantly older, had higher BMI, skin to liver capsule distance, TE liver stiffness measurement, alcohol consumption, and blood based assessments AST (but not ALT), AST/ALT ratio, AST to platelet ratio index (APRI), Fibrosis-4 index (FIB-4), Hepascore and NAFLD fibrosis score (NFS), but lower platelet count and serum albumin (p < 0.05 for all). There was a strong correlation between SWE and TE liver stiffness measurement (r = 0.77, p < 001). The strength of correlation between SWE and TE varied by aetiology of liver disease; alcohol (r = 0.6, p = 0.005), hepatitis B (r = 0.5, p < 0.001), hepatitis C (r = 0.73, p < 0.001), NAFLD (r = 0.87, p < 0.001). Using multiple logistic regression analysis, independent predictors of significant liver fibrosis using either SWE or TE were FIB-4, BMI and male sex (after adjusting for other covariates). SWE was found to be a useful test for suspected liver fibrosis in various liver disorders, and results were found to correlate with TE liver stiffness measurement plus clinically relevant anthropometric and laboratory parameters. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Globally, B‐mode ultrasound is the most common modality used for the diagnosis of hepatic steatosis. We aimed to assess the correlation between qualitative liver ultrasound parameters, attenuation imaging (ATI) and histopathology‐diagnosed steatosis grade obtained from liver biopsy. Our secondary aim was to examine the interobserver variability of qualitative ultrasound features.A retrospective cohort study was performed which included adult patients (age ≥ 18 years) who had same‐day liver ultrasound, ATI and liver biopsy for grading hepatic steatosis severity between 2018 and 2022. The qualitative US features for hepatic steatosis were independently scored by three radiologists and interobserver variability was examined. Histologic steatosis grade, ATI and qualitative ultrasound parameters were compared.Ninety patients were included; 67% female with a median age of 54 (IQR 39–65) years. The radiologist's overall impression had the highest correlation (very strongly correlated) with histologic steatosis grade (r = 0.82, P < 0.001). ATI coefficient and all qualitative ultrasound B‐mode features except for liver echotexture and focal fat sparing were strongly correlated with histologic steatosis grade (r ≥ 0.70, P < 0.001). Most qualitative ultrasound features had good agreement between observers (Kappa statistic 0.61–1.0, P < 0.001), (Kendall coefficient 0.92, P < 0.001).The examined qualitative ultrasound parameters and ATI had good‐excellent performance for diagnosing clinically significant hepatic steatosis; however, the radiologist's overall impression had the best correlation with histologic steatosis grade. Our findings suggest an ongoing role for qualitative liver ultrasound assessment of hepatic steatosis despite the emergence of newer quantitative measures. [ABSTRACT FROM AUTHOR]

The authors discuss the significance of platelet count, aspartate aminotransferase (AST), Haptoglobin, and Apolipoprotein-A1 (PAHA) model in predicting liver cirrhosis in patients with chronic Hepatitis B (CHB) infection. They tackle the superiority of PAHA models compared to other liver cirrhosis predictors in patients with CHB infection. They assert that the PAHA model is critical to several clinicians who manage CHB in the Asia-Pacific region.

Introduction: 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. Methods: 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. Results: The median patient age was 50.5 (range 18–83) years and BMI 28.9 kg/m2 (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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Cannabis is one of the most common non‐prescribed psychoactive substances used in pregnancy. The prevalence of gestational cannabis use is increasing. Aim: The aim was to examine the prevalence of gestational cannabis use and associated pregnancy and neonate outcomes. Materials and Methods: 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. Results: 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). Conclusion: Gestational cannabis use was independently associated with low birthweight, synergistically affected by tobacco smoking. [ABSTRACT FROM AUTHOR]

Background: 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.Study Design and Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background and Aim: Environmental factors including excessive caloric intake lead to disordered lipid metabolism and fatty liver disease (FLD). However, FLD demonstrates heritability suggesting genetic factors are also important. We aimed to use a candidate gene approach to examine the association between FLD and single nucleotide polymorphisms (SNPs) in lipid metabolism genes in the adolescent population-based Western Australian Pregnancy (Raine) Cohort. Methods: A total 951 seventeen year-olds underwent hepatic ultrasound, anthropometric and biochemical characterization, DNA extraction and genotyping for 57 SNPs in seven lipid metabolism genes (ApoB100, ATGL, ABHD5, MTTP, CETP, SREBP-1c, PPARα). Associations were adjusted for metabolic factors and Bonferroni corrected. Results: The prevalence of FLD was 16.2% (11.4% male vs 21.2% female, P = 0.001). Multivariate analysis of metabolic factors found suprailiac skinfold thickness (SST) to be the major predictor of FLD in females and males (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.08-1.15, P = 1.7 × 10−10 and OR 1.17, 95%CI 1.13-1.22, P = 2.4 × 10−11, respectively). In females, two SNPs in linkage disequilibrium from the CETP gene were associated with FLD: rs12447924 (OR 2.16, 95%CI 1.42-3.32, P = 0.0003) and rs12597002 (OR = 2.22, 95%CI 1.46-3.41 P = 0.0002). In lean homozygotes, the probability of FLD was over 30%, compared with 10-15% in lean heterozygotes and 3-5% in lean wild-types. However, these associations were modified by SST, such that for obese individuals, the probability of FLD was over 30% in all genotype groups. Conclusions: Cholesteryl ester transfer protein gene polymorphisms are associated with an increased risk of FLD in adolescent females. The effect is independent of adiposity in homozygotes, thereby placing lean individuals at a significant risk of FLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7–8.8)% and 2.4 (95% CI 2.2–2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69–0.93) and 0.990 (95% CI 0.985–0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF. [ABSTRACT FROM AUTHOR]

Background and Aims 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. Methods 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. Results 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). Conclusions 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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS:A Western dietary pattern at 14 years in a general population sample 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. [ABSTRACT FROM AUTHOR]

Objectives: Hepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases. Materials and Methods: Fifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations. Results: The MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r2 = 0.83) and computer-assisted morphometric (r2 = 0.84) estimates of hepatic steatosis from histological specimens. Conclusions: This MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases. [ABSTRACT FROM AUTHOR]