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.

Disparate age and sex distribution of sessile serrated lesions and conventional adenomas in an outpatient colonoscopy population-implications for colorectal cancer screening?

PURPOSE: Colorectal cancer (CRC) is increasingly diagnosed in individuals 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. METHODS: 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. RESULTS: 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/m2 (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). CONCLUSIONS: 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.

Prospective dietary polyunsaturated fatty acid intake is associated with trajectories of fatty liver disease: an 8 year follow-up study from adolescence to young adulthood.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is common and related to obesity and insulin resistance. Iron metabolism is impaired in obese individuals 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. METHODS: 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. X2 and linear regression analyses were used to compare characteristics of study participants according to NAFLD status at age 17 years. RESULTS: 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. CONCLUSIONS: 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.

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.

Importance of cardiometabolic risk factors in the association between nonalcoholic fatty liver disease and arterial stiffness in adolescents.

UNLABELLED: 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). CONCLUSION: 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.