The prevalence and significance of gestational cannabis use at an Australian tertiary hospital.

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.

Clinical relevance of shear wave elastography compared with transient elastography and other markers of liver fibrosis.

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.

Assessment of liver fibrosis markers in people with rheumatoid arthritis on methotrexate.

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.

Prior oral proton-pump inhibitor use is associated with reduced severity of aspirin-related upper gastrointestinal bleeding in older people.

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.

Sex differences between parental pregnancy characteristics and nonalcoholic fatty liver disease in adolescents.

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. (Hepatology 2018;67:108-122).

Bowel patterns, gastrointestinal symptoms, and emotional well-being in adolescents: A cohort study.

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.

Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents.

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 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. 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 ⩾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). CONCLUSION: 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. 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 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.

The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial.

UNLABELLED: Iron is implicated in the pathogenesis of liver injury and insulin resistance (IR) and thus phlebotomy has been proposed as a treatment for nonalcoholic fatty liver disease (NAFLD). We performed a prospective 6-month randomized, controlled trial examining the impact of phlebotomy on the background of lifestyle advice in patients with NAFLD. Primary endpoints were hepatic steatosis (HS; quantified by magnetic resonance imaging) and liver injury (determined by alanine aminotransaminase [ALT] and cytokeratin-18 [CK-18]). Secondary endpoints included insulin resistance measured by the insulin sensitivity index (ISI) and homeostasis model of assessment (HOMA), and systemic lipid peroxidation determined by plasma F2-isoprostane levels. A total of 74 subjects were randomized (33 phlebotomy and 41 control). The phlebotomy group underwent a median (range) of 7 (1-19) venesection sessions and had a significantly greater reduction in ferritin levels over 6 months, compared to controls (-148 ± 114 vs. -38 ± 89 ng/mL; P < 0.001). At 6 months, there was no difference between phlebotomy and control groups in HS (17.7% vs. 15.5%; P = 0.4), serum ALT (36 vs. 46 IU/L; P = 0.4), or CK-18 levels (175 vs. 196 U/L; P = 0.9). Similarly, there was no difference in end-of-study ISI (2.5 vs. 2.7; P = 0.9), HOMA (3.2 vs. 3.2; P = 0.6), or F2-isoprostane levels (1,332 vs. 1,190 pmmol/L; P = 0.6) between phlebotomy and control groups. No differences in any endpoint were noted in patients with hyperferritinemia at baseline. Among patients undergoing phlebotomy, there was no correlation between number of phlebotomy sessions and change in HS, liver injury, or IR from baseline to end of study. CONCLUSION: Reduction in ferritin by phlebotomy does not improve liver enzymes, hepatic fat, or IR in subjects with NAFLD.

Red blood cell transfusion is associated with further bleeding and fresh-frozen plasma with mortality in nonvariceal upper gastrointestinal bleeding.

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.

Adverse metabolic phenotype of adolescent girls with non-alcoholic fatty liver disease plus polycystic ovary syndrome compared with other girls and boys.

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.

Texture-based classification of liver fibrosis using MRI.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Childhood adiposity trajectories and risk of nonalcoholic fatty liver disease in adolescents.

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.

Association between liver-specific gene polymorphisms and their expression levels with nonalcoholic fatty liver disease.

UNLABELLED: 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 samples 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). CONCLUSION: The association between GC and LCP1 SNPs and NAFLD as well as altered biological expression implicate these genes in the pathogenesis of NAFLD.

Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity.

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.

Lower fructose intake may help protect against development of nonalcoholic fatty liver in adolescents with obesity.

OBJECTIVES: Although obesity is a major risk factor for nonalcoholic fatty liver (NAFL), not all individuals with obesity develop the condition, suggesting that other factors such as diet may also contribute to NAFL development. We evaluated associations between fructose and total sugar intake and subsequent diagnosis of NAFL in adolescents with obesity and without obesity in a population-based cohort. METHODS: Adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study completed 3-day food records and body mass index measurement at age 14 years. At age 17 years, participants underwent abdominal ultrasound to determine NAFL status. Multivariable logistic regression models were used to analyse associations between energy-adjusted fructose and total sugar intake and NAFL status. Food diaries and liver assessments were completed for 592 adolescents. RESULTS: The prevalence of NAFL at age 17 was 12.8% for the total group and 50% for adolescents with obesity. Fructose intake did not significantly differ between adolescents with or without NAFL in our cohort as a whole. Among adolescents with obesity, those without NAFL had significantly lower energy-adjusted fructose intake at age 14 years compared with those with NAFL (mean ± standard deviation [SD] 38.8 ± 19.8 g/day, vs 55.7 ± 14.4 g/day, P = 0.02). Energy-adjusted fructose intake was independently associated with NAFL in adolescents with obesity (OR [odds ratio] 1.09, 95% CI 1.01-1.19, P = 0.03) after the adjustment for confounding factors. Energy-adjusted total sugar intake showed less significance (OR 1.03, 95% CI 0.999-1.07, P = 0.06). No significant associations were observed in other body mass index categories. CONCLUSIONS: Lower fructose consumption in adolescents with obesity at 14 years is associated with a decreased risk of NAFL at 17 years. Fructose rather than overall sugar intake may be more physiologically relevant in this association.

The Western dietary pattern is prospectively associated with nonalcoholic fatty liver disease in adolescence.

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.

Hepatic steatosis: Ultrasound assessment using attenuation imaging (ATI) with liver biopsy correlation.

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.