Primary Nonalcoholic Fatty Liver Disease Research Articles

Co-Morbid Hypothyroidism and Liver Dysfunction: A Review.

The liver and thyroid hormones interact at multiple levels to maintain homoeostasis. The liver requires large adequate amounts of thyroid hormones to execute its metabolic functions optimally, and deficiency of thyroid hormones may lead to liver dysfunction. Hypothyroidism has been associated with abnormal lipid metabolism, non-alcoholic fatty liver disease (NAFLD), hypothyroidism-induced myopathy, hypothyroidism-associated gallstones and occasionally, interferon-induced thyroid dysfunction. NAFLD remain an important association with hypothyroidism and further studies are needed that specifically compare the natural course of NAFLD secondary to hypothyroidism and primary NAFLD. Hepatic dysfunction associated with hypothyroidism is usually reverted by normalizing thyroid status. Large scale studies geared towards finding new and effective therapies, especially for NAFLD are needed. The clinician must be aware that there exists overlapping symptomatology between liver dysfunction and severe hypothyroidism which may make delay the diagnosis and treatment of hypothyroidism; this requires a high index of suspicion.

Comparison of structural and functional vascular disorders in patients with comorbidity of non-alcoholic fatty liver disease and two types of arterial hypertension

Background: The aim was to conduct a comparative assessment of structural and functional vascular disorders in patiets with comorbidity of non-alcoholic fatty liver disease (NAFLD) and two types of arterial hypertension (HTN). Material and methods: The study included 329 patients 18–66 years old. All patients were divided into five groups: patients with comorbidity of NAFLD and primary HTN (121 subjects), patients with comorbidity of NAFLD and renal parenchymal HTN (88 subjects), patients with NAFLD (60 subjects), patients with primary HTN (30 subjects), patients with renal parenchymal HTN (30 people). The control group consisted of 20 healthy individuals of similar age and gender categories. Results: In the comparative analysis of the structural and functional ultrasonographic parameters of vessels, no significant differences between two comorbidity groups NAFLD + primary HTN and NAFLD + renal parenchymal HTN were found. The influence of AH and degree of liver steatosis on ultrasound indicators of arteries in examined patients with comorbidity was evaluated by MANOVA analysis. The influence of the HTN factor and the influence of the liver steatosis factor were evaluated separately, after which the influence of the comorbidity factor, i.e., the combined influence of these factors and one or another indicator, was evaluated. The additive effect of the factors of AH and liver steatosis was identified according to the parameters: intima media thickness, pulse wave velocity in the carotid artery, pulse wave velocity in the abdominal aorta and endothelial-related vasodilation, which indicates an important comorbid effect of NAFLD and primary/renal parenchymal HTN on the structural and functional state of arteries. Conclusions: There are no differences between the structural and functional indicators of arteries in patients with comorbidity of NAFLD + primary HTN and NAFLD + renal parenchymal HTN. The factor of the presence of HTN and the degree of liver steatosis significantly affect structural and functional indicators of the studied arteries.

Non-alcoholic fatty liver disease is not associated with impairment in health-related quality of life in virally suppressed persons with human immune deficiency virus.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups. Prospectively enrolled 200 PWH and 474 participants with primary NAFLD completed the Rand SF-36 assessment which measures 8 domains of HRQOL. Individual domain scores were used to create composite physical and mental component summary scores. Univariate and multivariate analyses determined variables associated with HRQOL in PWH and in HIV- and primary NAFLD. In PWH, 48% had HIV-NAFLD, 10.2% had clinically significant fibrosis, 99.5% were on antiretroviral therapy, and 96.5% had HIV RNA <200 copies/ml. There was no difference in HRQOL in PWH with or without NAFLD. Diabetes, non-Hispanic ethnicity, and nadir CD4 counts were independently associated with impaired HRQOL in PWH. In HIV-NAFLD, HRQOL did not differ between participants with or without clinically significant fibrosis. Participants with HIV-NAFLD compared to those with primary NAFLD were less frequently cisgender females, White, more frequently Hispanic, had lower BMI and lower frequency of obesity and diabetes. HRQOL of individuals with HIV-NAFLD was not significantly different from those with primary NAFLD. In conclusion, in virally suppressed PWH, HRQOL is not different between participants with or without HIV-NAFLD. HRQOL is not different between HIV-NAFLD and primary NAFLD.

Dietary Acid Load (DAL), Glycated Hemoglobin A1c (HbA1c), and Metabolic Syndrome (MeS) Mediate the Association of the Adherence to the Dietary Approaches to Stopping Hypertension (DASH) and Mediterranean Diet (MeD) With Nonalcoholic Fatty Liver Disease.

The study aimed to investigate the association of adults adhering to Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet (MeD) with nonalcoholic fatty liver disease (NAFLD) using structural equation modeling (SEM) in Iran. In this population-based cross-sectional study, 3,220 adults (44.65% female) aged ≥18 years were selected from the Amol Cohort Study (AmolCS). The dietary intakes were assessed by a validated 168-item semi-quantitative food-frequency questionnaire (FFQ). Residual method energy adjustment of MeD and DASH scores were calculated. Demographic characteristics and anthropometric and laboratory measurements were collected. NAFLD was diagnosed by an expert radiologist via ultrasound sonography. Based on the primary hypothesis, DASH, MeD, and NAFLD were fitted into models. Metabolic syndrome (MeS) as a potential risk factor directly affected NAFLD risk in all these models. In both genders, the higher adherence to DASH negatively affected NAFLD risk indirectly through the two following paths. (1) Dietary acid load (DAL) and metabolic syndrome (2) DAL and hemoglobin A1c (HbA1c). In addition, the higher DAL positively affected NAFLD risk among male participants indirectly via increasing HbA1c level and MeS (from DAL to HbA1c: β = 0.07, P < 0.001; from HbA1c to MeS: β = 0.10, P < 0.001). Similarly, in both genders, the relationship between MeD and NAFLD was mediated through (1) DAL, HbA1c, and MeS and (2) DAL and MeS. Further, among male participants, the MeD and NAFLD risk were also associated via the mediators of HbA1c and MeS. In female participants, the higher MeD score was directly associated with a reduction of NAFLD risk (β = −0.07, P = 0.008). The present study found three important mediators, including DAL, HbA1c, and MeS, in the association of DASH and MeD scores with NAFLD risk. Preventive and therapeutic interventions should target the mediators, including DAL, HbA1c, MeS, and its components, to reduce NAFLD incidence in the general population.

Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction.

Primary nonalcoholic fatty liver disease (NAFLD) is bi-directionally associated with the metabolic syndrome and its constitutive features (“factors”: impaired glucose disposal, visceral obesity, arterial hypertension, and dyslipidemia). Secondary NAFLD occurs due to endocrinologic disturbances or other cofactors. This nosography tends to be outdated by the novel definition of metabolic associated fatty liver disease (MAFLD). Irrespective of nomenclature, this condition exhibits a remarkable pathogenic heterogeneity with unpredictable clinical outcomes which are heavily influenced by liver histology changes. Genetics and epigenetics, lifestyle habits [including diet and physical (in)activity] and immunity/infection appear to be major cofactors that modulate NAFLD/MAFLD outcomes, including organ dysfunction owing to liver cirrhosis and hepatocellular carcinoma, type 2 diabetes, chronic kidney disease, heart failure, and sarcopenia. The identification of cofactors for organ dysfunction that may help understand disease heterogeneity and reliably support inherently personalized medicine approaches is a research priority, thus paving the way for innovative treatment strategies.

Non-alcoholic fatty liver disease - a look at diagnostic prospects

This article observes the main trends in the diagnosis of non-alcoholic hepatic steatosis, which have been observed in world practice recently. From a practical point of view, one of the most significant events was the introduction of a new term “metabolically associated fatty liver disease” (MAFLD), which partly replaced the previously used term “primary non-alcoholic fatty liver disease”. The new nomenclature induces clear diagnostic criteria for MAFLD, and this disease has ceased to be a diagnosis of exclusion, as a result. In the near future, the practical aspects of the application of this nomenclature and new diagnostic criteria are to be evaluated. The second important trend is the increasing role of direct serum markers of liver fibrosis in the diagnosis and prognosis of MAFLD. Thus, collagen type 3 propeptide (PRO-C3), as well as M2BPGi (Mac2 Binding Proteine Glycosylation isomer), look very promising, since research data have demonstrated a higher diagnostic value of these markers in comparison with indirect fibrosis indices, which are most often used in clinical practice. In addition, the search continues for new direct serum markers of fibrosis, which would be more sensitive for detecting liver fibrosis of stages 1-2. In general, one should expect a gradual replacement by serological markers of fibrosis of technically more complex and expensive diagnostic methods, such as magnetic resonance elastography and fibroelastometry.

Correlation between Non-Alcoholic Fatty Liver Disease (NAFLD) fibrosis score (NFS) with Left Ventricular Mass Index (LVMI) in patients with NAFLD

Background: Cardiovascular-related mortality is a major concern in NAFLD. Advanced fibrosis was known to be associated with cardiovascular diseases. NAFLD Fibrosis Score (NFS) is used to identify the development of liver fibrosis in NAFLD patients. Left ventricular mass index (LVMI) is a sign of subclinical cardiovascular complications in NAFLD. The correlation between NAFLD fibrosis score with LVMI in NAFLD patients is not fully established.Objective: To analyze the correlation between NAFLD fibrosis score with LVMI in NAFLD patients.Methods: A cross-sectional study of NAFLD patients in Kariadi Hospital Indonesia. NFS was done using a formula based on clinical and biochemical parameters. LVMI was measured with echocardiography. Pearson’s, Mann-Whitney, and logistic regression were used for analysis.Results: A total of 64 patients with primary NAFLD were enrolled, 54.7% males and 45.3% females. Mean age was 52,8 ± 10,5 years (30-77 years). Based on NFS criteria, high probability group was the highest (50%), followed by intermediate probability group (34,4%) and low probability group (15,6%). Highest increase in LVMI was obtained in the high probability group (93,8%), followed by intermediate probability (59,1%), and low probability group (10%) respectively. There was significant correlation between NFS and LVMI (P 0,002). Logistic regression showed that NFS has a more significant correlation with LVMI compared to gender (P=0,002).Conclusion: NFS is a non‐invasive liver fibrosis scores which independently corelated with Left ventricular mass index (LVMI), a marker of cardiovascular abnormality.

Identifying Patients at Risk for Fibrosis in a Primary Care NAFLD Cohort.

Using natural language processing to create a nonalcoholic fatty liver disease (NAFLD) cohort in primary care, we assessed advanced fibrosis risk with the Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Score (NFS) and evaluated risk score agreement. In this retrospective study of adults with radiographic evidence of hepatic steatosis, we calculated patient-level FIB-4 and NFS scores and categorized them by fibrosis risk. Risk category and risk score agreement was analyzed using weighted κ, Pearson correlation, and Bland-Altman analysis. A multinomial logistic regression model evaluated associations between clinical variables and discrepant FIB-4 and NFS results. Of the 767 patient cohorts, 71% had a FIB-4 or NFS score in the indeterminate-risk or high-risk category for fibrosis. Risk categories disagreed in 43%, and scores would have resulted in different clinical decisions in 30% of the sample. The weighted κ statistic for risk category agreement was 0.41 [95% confidence interval (CI): 0.36-0.46] and the Pearson correlation coefficient for log FIB-4 and NFS was 0.66 (95% CI: 0.62-0.70). The multinomial logistic regression analysis identified black race (odds ratio=2.64, 95% CI: 1.84-3.78) and hemoglobin A1c (odds ratio=1.37, 95% CI: 1.23-1.52) with higher odds of having an NFS risk category exceeding FIB-4. In a primary care NAFLD cohort, many patients had elevated FIB-4 and NFS risk scores and these risk categories were often in disagreement. The choice between FIB-4 and NFS for fibrosis risk assessment can impact clinical decision-making and may contribute to disparities of care.

Primary Versus Secondary NAFLD: Perspective on Advanced Fibrosis

The presence of macrovesicular steatosis on liver biopsy is the commonest histopathological finding. Nonalcoholic fatty liver disease (NAFLD) is the presence of ≥5% macrovesicular steatosis without significant alcohol use. It is subdivided into primary and secondary NAFLD; information on their differences is limited. To determine the histopathological differences between primary and secondary NAFLD and establish whether the prevalence of advanced fibrosis varies between the two types. Three years of retrospective study of 90 liver biopsies with ≥5% macrovesicular steatosis. Age, gender, clinical history, serum transaminaselevels were noted. The biopsy was reviewed for steatosis, inflammation, and fibrosis. Differences between primary and secondary NAFLD for age, gender, AST/ALT ratio, histopathological features were determined. Descriptive statistical analysis, 2-tailed Student's t test, Chi-square test, Fisher's exact test were used, where p<0.05 was considered significant. Primary and secondary NAFLD were 42 (46.7%) and 48 (53.3%), respectively. Inflammation was noted in 50 (55.5%) and fibrosis in 31 (34.4%). The prevalence of advanced fibrosis was 24.4%. Primary and secondary NAFLD differed significantly on ballooning degeneration, Mallory Denk bodies (MDBs), glycogenated nuclei, and fibrosis stage (p < 0.05). There were no significant differences among AST/ALT ratio, steatosis, and inflammation grade. Primary NAFLD is a more severe type of liver disease. On histopathology, ballooning degeneration, MDBs, glycogenated nuclei, and advanced fibrosis was more prevalent in primary than secondary NAFLD.

Non-Alcoholic Fatty Liver Disease in Primary Hypothyroidism

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition world-wide. Hypothyroidism is also a common disorder affecting general population especially in women.&#x0D; Objectives: To determine the association between primary hypothyroidism and NAFLD.&#x0D; Materials and Method: This is a cross-sectional descriptive type of observational study where 100 cases of primary hypothyroidism in age group 15-75 years of both sexes were selected from February 2018 to January 2019 in CMH Momenshahi having higher level of Thyroid stimulating hormone(TSH). In all cases ultra-sonogram of hepatobiliary system was done by efficient sonologist who was blind about clinical scenario of the patients.&#x0D; Results: Mean age of patients 29±SD7.57.Among 100 cases 56(56%) having NAFLD among them 95% were female and 5% were male.&#x0D; Conclusion: NAFLD was significantly correlated with primary hypothyroidism.&#x0D; JAFMC Bangladesh. Vol 15, No 2 (December) 2019: 206-208

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard. Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%). Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%. The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

FRI005 - Performance of non-invasive fibrosis tests among non-alcoholic fatty liver disease (NAFLD) patients with normal alanine aminotransferase (ALT): data from a large North American primary care NAFLD pathway

FRI005 - Performance of non-invasive fibrosis tests among non-alcoholic fatty liver disease (NAFLD) patients with normal alanine aminotransferase (ALT): data from a large North American primary care NAFLD pathway

Evaluation of Cardiovascular Risk in Patient with Primary Non-alcoholic Fatty Liver Disease.

The study aimed to investigate, in patients with primary non-alcoholic fatty liver disease (NAFLD), the presence of possible relationships between the degree of steatosis or fibrosis and the individual cardiovascular risk and possibly whether a difference between those various methods exists. Thirty-four adult patients with primary NAFLD were included in this study. Clinical evaluation included an ultrasonographic examination for the determination of the severity of steatosis. Two different clinical indirect indexes of the severity of hepatic fibrosis were used: the FIB-4 score and the NAFLD fibrosis score. Then, the individual cardiovascular 10-years risk according to 5 different scores: "Progetto Cuore" of the Italian Institute of Health, Framingham score 2004-ATP III, Framingham risk score 2008, ACC/AHA ASCVD risk score 2013, ACC/AHA ASCV risk score new model score 2 were estimated. The severity of steatosis evaluated by ultrasonography was significantly correlated only with ACC/AHA ASCVD RISK 2013, ACC/AHA ASCVD New Model 2 2018 and Framingham 2008 risk scores. The severity of fibrosis evaluated by the FIB-4 score or with NAFLD fibrosis score was significantly correlated only with cardiovascular risk evaluated with ACC/AHA ASCVD 2013, ACC/AHA ASCVD New Model 2 2018 and Framingham risk score 2008. Some of the methods for the estimation of cardiovascular risk (ACC/AHA ASCVD 2013, new model 2 2018, and, also Framingham score 2008) have a clear advantage over Framingham score 2004 and "Progetto Cuore" of the Italian Institute of Health in terms of correlation with the severity of NAFLD. They are, therefore, more clinically useful.

Causes of secondary non-alcoholic fatty liver disease in non-obese children below 10 years.

This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children < 10years from hepatologist perspectives. Infants and children below 10years of age with biopsy-proven fatty liver over a 6-year period were included. NAFLD activity score was used to detect the presence of non-alcoholic steatohepatitis (NASH). The study included 66 cases whose age ranged between 5months and 10years. Transaminases were elevated in 60% patients. Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). The cause of steatosis could not be identified in 28.8% of cases. There was a higher prevalence of secondary causes of NAFLD in patients < 10years. Liver histopathological examination revealed preserved lobular architecture in 75.7% with minimal-to-mild fibrosis in 79%. Steatosis was macrovesicular in all specimens (severe steatosis in 39.4%). Four patients had NASH. Higher degree of steatosis was associated with more severe fibrosis (P = 0.01).Conclusion: GSD was the commonest cause of secondary NAFLD in Egyptian children < 10years followed by HCV and CDS with higher degrees of steatosis in younger patients. The degree of fibrosis was significantly related to the degree of steatosis.What is Known:• Primary non-alcoholic fatty liver disease (NAFLD) is rare in children aged less than 10years.• Secondary causes of NAFLD should be considered in patients who do not have traditional risk factors.What is New:• Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (< 10years) with higher degrees of steatosis in younger patients.• The degree of liver fibrosis is significantly related to the degree of steatosis.

MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n=25) or placebo (n=25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2±10.3 years and 30.7±4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P=0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P=0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P=0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management.

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.

Nonalcoholic Fatty Liver Disease in Children.

Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown. Understanding the pathogenetic mechanisms provides the basis to characterize early predictors of the disease and noninvasive diagnostic tools and to design novel specific treatments and possible management strategies. Despite a few clinical trials on the use of antioxidants combined with lifestyle intervention for NAFLD, no treatment exists for children with NAFLD. In this review, the authors provide an overview of current concepts in epidemiology, histological features, etiopathogenesis, diagnosis, and treatment of NAFLD in pediatric population.

Body mass index trajectories in young adulthood predict non-alcoholic fatty liver disease in middle age: The CARDIA cohort study.

Non-alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for non-alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25-year patterns of body mass index change are associated with midlife non-alcoholic fatty liver disease. In all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective population-based biracial cohort (age 18-30), underwent body mass index measurement at baseline (1985-1986) and 3 or more times over 25years. At Year 25, 3115 had liver fat assessed by non-contrast computed tomography. Non-alcoholic fatty liver disease was defined as liver attenuation ≤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25-year trajectories in body mass index per cent change (%Δ) from baseline. We identified four distinct trajectories of BMI%Δ: stable (26.2% of cohort, 25-year BMI %Δ=3.1%), moderate increase (46.0%, BMI%Δ=21.7%), high increase (20.9%, BMI%Δ=41.9%) and extreme increase (6.9%, BMI%Δ=65.9%). Y25 non-alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Δ: 4.1%, 9.3%, 13.0%, and 17.6%, respectively (P-trend <.0001). In multivariable analyses, participants with increasing BMI%Δ had increasingly greater odds of non-alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07-5.42), 7.80 (4.60-13.23) and 12.68 (6.68-24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index. Trajectories of weight gain during young adulthood are associated with greater non-alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary non-alcoholic fatty liver disease prevention.

P1243 : Birth cohort distribution and screening of viremic HCV infections in luxembourg

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease in children, with an estimated prevalence of 5–10%. The majority of published data has involved Caucasians. Data is lacking regarding the phenotypic differences of NAFLD in children of Asian origin. Methods: We performed a retrospective review of children consecutively diagnosed with NAFLD at a tertiary referral hepatology service in the UK, between 2003 and 2014. Patients had been referred from either primary care physicians or general paediatricians with incidental asymptomatic abnormal liver function tests (LFTs) and/or fatty liver on ultrasound scan (USS). Patients with inadequate data or with secondary fatty liver disease were excluded. Patients were divided by ethnicity into Asian and Caucasian. All values are (±SD), unless stated. Results: 100 patients with primary NAFLD were identified. 59/100 were Caucasian and 41/100 were of Asian origin, of whom, 73% (30/41) were Pakistani. There was male predominance in both groups, 73% (43/59) in Caucasian and 78% (32/41) in Asians. Mean ages at presentation were 12.6±2.5 and 11.7±2.8 years in Caucasian and Asian groups, respectively. Asian patients had a significantly lower body mass index (BMI) centile than Caucasian (91.2±9.5 vs. 96.1±5.1, p < 0.05). There were no differences in LFTs between Asian and Caucasian patients, ALT (87.8±60.9 vs. 94.3±84.5 IU/L) and bilirubin (9.4±7.6 vs. 9±6.5mmol/L). 61% (25/41) Asian patients had an elevated gamma glutamyl transferase, compared to 60% (35/59) Caucasian patients. Markers of the metabolic syndrome were similar in both groups: total cholesterol 4.4±1 vs. 4.4±1mg/L, triglycerides 2.0±1.4 vs. 2.2±1.4mg/L, and HbA1c 38.6 vs. 39.1±7.4mmol/mol. 20 patients had undergone biopsy. 33% (2/6) demonstrated moderate-severe fibrosis in Asian patients, compared to 21% (3/14) Caucasian patients (p =0.61). Conclusions: Asian children with NAFLD have similar disease severity as their Caucasian counterparts, despite a significantly lower BMI centile at presentation. Referring clinicians and risk stratification scores require a greater awareness of ethnic differences in adiposity in paediatric NAFLD. EU Public health

Clinical, biochemical and histological differences between HIV-associated NAFLD and primary NAFLD: a case-control study.

There are limited data regarding the clinical, biochemical and liver histological characteristics of patients with HIV-associated nonalcoholic fatty liver disease (NAFLD), and whether this entity differs in presentation and severity from primary NAFLD AIM: To examine the clinical and histological differences between HIV-associated NAFLD and primary NAFLD. This is a cross-sectional, case-control study comparing patients with HIV-associated NAFLD vs. patients with primary NAFLD. HIV-infected patients were identified from a database of consecutive liver biopsies performed at the University of California at San Diego, over a 13-year period. HIV-infected patients with biopsy-proven NAFLD were selected as cases, after exclusion of other causes of liver disease and hepatic steatosis. Age-sex-matched controls with biopsy-proven primary NAFLD were randomly identified from the same pathology database. All biopsies underwent a standardised, detailed, histological research evaluation by a liver pathologist who was blinded to clinical and case-control status. Compared to age-sex-matched patients with primary NAFLD (n = 33), patients with HIV-associated NAFLD (n = 33) had significantly higher mean aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.001), alkaline phosphatase (P = 0.003) and serum triglycerides (P = 0.024). Similarly, compared to age-sex-matched primary NAFLD, patients with HIV-associated NAFLD had significantly higher rates of definite steatohepatitis (37% vs. 63%, P = 0.04), and more features of liver injury, including lobular inflammation (<0.001) and acidophil bodies (<0.001). Compared to age-sex-matched primary NAFLD, HIV-associated NAFLD has increased severity of liver disease and a higher prevalence of NASH.