Presence Of Hepatic Steatosis Research Articles

Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging–Proton Density Fat Fraction as the Standard

Controlled attenuation parameter (CAP) measurements using M probe have been reported to be lower than those of the XL-probe in detection of hepatic steatosis. However, there has been no direct comparison of CAP with the M vs the XL probe in patients with nonalcoholic fatty liver disease (NAFLD). We compared CAP with the M vs the XL probe for quantification of hepatic fat content, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the standard. We performed a prospective study of 100 adults (mean body mass index [BMI], 30.6 ± 4.7 kg/m2) with and without NAFLD, assessed by CAP with the M probe and XL probe on the same day, at a single research center, from November 2017 through November 2018. We then measured the MRI-PDFF as the reference standard. Outcomes were presence of hepatic steatosis, defined as MRI-PDFF ≥ 5%, and detection of hepatic fat content ≥ 10%, defined as MRI-PDFF ≥ 10%. We performed area under the receiver operating characteristic curve (AUROC) analyses to assess the diagnostic accuracy of CAP for each probe in detection of hepatic steatosis (MRI-PDFF ≥ 5%) and of hepatic fat content ≥ 10%. Of the study participants, 68% had an MRI-PDFF of 5% or more and 48% had an MRI-PDFF of 10% or more. The mean CAP measured by the M probe (310 ± 62 db/m) was significantly lower than by the X probe (317 ± 63 db/m) (P = .007). When M probe was used in participants with BMIs <30 kg/m2 and XL probe in participants with BMIs ≥30 kg/m2, the CAP measured by the M probe (312 ± 51.4 db/m) remained significantly lower than that of the XL probe (345 ± 47.6 db/m) (P = .0035.), when the MRI-PDFF was above 5%. The optimal threshold of CAP for the detection of MRI-PDFF≥5%, was 294 db/m with the M probe and 307 db/m with the XL probe. The optimal threshold of CAP for the detection of MRI-PDFF ≥ 10%, was 311 db/m with the M probe and 322 db/m with the XL probe. For only the XL probe, CAP measurements with an interquartile range below 30 dB/m detected an MRI-PDFF≥5% with a lower AUROC (0.97; 95% CI, 0.80-1.00) than CAP measurements with an interquartile range above 30 dB/m (AUROC, 0.82; 95% CI, 0.71-0.90) (P = .0129). In an analysis of the same patients using CAP with the M probe and XL probe, with MRI-PDFF as the standard, we found that the M probe under-quantifies CAP values compared with the XL probe, independent of BMI. The type of probe should be considered when interpreting CAP data from patients with NAFLD.

Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study

BackgroundNon-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants.MethodsAmong the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out.ResultsWe recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17).DiscussionGiven the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.

The impact of modifiable risk factors on the long-term outcomes of non-alcoholic fatty liver disease.

Cardiovascular (CV) disease is the leading cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD). The American Heart Association (AHA) developed 7 CV health metrics (poor, intermediate and ideal health) to improve CV health. To assess population-attributable fractions (PAFs) of CV health metrics to all-cause and CV mortality among NAFLD patients METHODS: We included adult participants from National Health and Nutrition Examination Survey (NHANES 1988-1994) with clinical and mortality data. NAFLD was defined as the presence of hepatic steatosis on ultrasonography in the absence of other chronic liver diseases and excessive alcohol use. A total of 4040 adults with NAFLD and 7515 without were included. NAFLD had fewer ideal health metrics than non-NAFLD (age-standardised prevalence: 20% vs 10% for ≤1 ideal health metric; 5.1% vs 8.7% for ≥6, all P<.001). Following median follow-up of 19.2years (IQR: 17.5-21.0years), 1,136 NAFLD subjects (327 CV deaths) and 1600 non-NAFLD subjects (447 CV deaths) died. Increased number of ideal health metrics (all trend P<.0001) correlated with lower risk for all-cause and CV mortality. If all NAFLD subjects achieved 7 ideal health metrics, 66% of all-cause deaths and 83% of CV deaths were preventable. Among NAFLD subjects, lack of glycaemic control (adjusted PAF=28.3% all-cause; 38.1% CV) and hypertension (adjusted PAF of 23% all-cause; 52.8% CV) were the largest mortality contributors. Ideal physical activity level obtainment provided an adjusted PAF=13.9% all-cause and 13.8% CV mortality. Attainment of ideal CV health metrics provides protection against all-cause and CV deaths in NAFLD.

Sarcopenia is associated with non-alcoholic fatty liver disease in men with type 2 diabetes

AimsRecent epidemiological studies have suggested an association between sarcopenia and non-alcoholic fatty liver disease (NAFLD) in the general population, prompting our investigation into the gender-specific association between sarcopenia and NAFLD in patients with type 2 diabetes mellitus (T2DM). MethodsIn this cross-sectional study, 4210 patients with T2DM were recruited from the Seoul Metabolic Syndrome Cohort. Appendicular skeletal muscle mass (ASM) was estimated from bioimpedance analysis measurements, and the skeletal muscle mass index (SMI) was calculated by dividing the sum of ASM by body weight. Sarcopenia was defined as a gender-specific SMI value>2 standard deviations (SDs) below the mean for healthy young adults. NAFLD was defined as the presence of hepatic steatosis on ultrasonography with no other causes of chronic liver disease. ResultsAmong the entire study population (mean age: 57.4±10.8 years), 1278 (30.4%) had NAFLD and 1240 (29.5%) had sarcopenia, and the prevalence of NAFLD was significantly higher in those with sarcopenia: 46.2% vs 25.1% (P<0.001) in men; 38.3% vs 25.4% (P<0.001) in women. Sarcopenia was significantly associated with higher risk of NAFLD in men (adjusted odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.15–2.17), whereas the association was attenuated in women after adjusting for clinical risk factors. ConclusionSarcopenia is independently associated with NAFLD in men with T2DM, which suggests that sarcopenia may be a risk factor for NAFLD in men with T2DM.

Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA.

Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis. Cross-sectional data from 11 325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index. NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01-2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03-1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18-2.72). Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.

Metabolomic Characterization of a Novel Pig Model of Pediatric Non-alcoholic Fatty Liver Disease (P08-131-19)

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is a leading nutrition-linked liver disease in children. We have recently identified the neonatal Iberian pig as a novel model of pediatric NAFLD. Interestingly, feeding a high fructose-high fat (HFF) diet to neonatal Iberian pigs for 10 weeks did not induce obesity and decreased high and low density lipoproteins in serum, while the liver exhibited many of the histological features of pediatric NAFLD. In this study we utilized a metabolomics approach to characterize the metabolic phenotype of this pig model. MethodsPlasma and liver samples collected from Iberian pigs fed control, HFF, control + probiotic and HFF + probiotic diets were analyzed by LC-MS using targeted assays for primary metabolomics, aminomics, and lipidomics. Data was analyzed with multivariate statistics and 2-way ANOVA with t-tests adjusted for false discovery rate. ResultsResults from multivariate tests indicated no diet × probiotic interaction or probiotic effect, so only the main effect of diet is shown. A total of 224 and 218 metabolites were identified in the plasma and liver, respectively. In agreement with previous NAFLD models, the HFF diet increased hepatic branched chain amino acids, cholesteryl esters, hydroxyproline, plasma acylcarnitines and primary bile acids, and altered hepatic triacylglycerol-species composition (P < 0.0001). In addition, HFF pigs had increased homocysteine and methionine levels combined with a decrease in pyridoxate in liver (P < 0.0001), suggesting a disruption in the one carbon cycle and its methyl donation capability. HFF decreased hepatic choline and betaine (P < 0.0001), which may indicate a compensatory use of the methyl groups of these compounds. The aforementioned reduction of choline used for the CDP-choline pathway and the potential one carbon cycle impact on SAM availability for the phosphatidylethanolamine N-methyltransferase (PEMT) pathway may explain the observed differential changes in hepatic phosphatidylcholines (P < 0.0001), which are required for the production of very low density lipoproteins (VLDL). ConclusionsUnique features of this model such as reduced plasma lipoproteins and lack of weight gain in the presence of hepatic steatosis may be related to an altered one carbon cycle impacting phosphatidylcholine production. Funding SourcesARI, AcornSeekers.

1443-P: The Association between Hepatic Steatosis and Skeletal Muscle Mass Index in Korean Patients with Type 2 Diabetes

Background and Aims: Recent epidemiological studies have suggested the association between sarcopenia and nonalcoholic fatty liver disease (NAFLD) in the general population. However, the association between skeletal muscle mass and hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) has not been well studied. Therefore, we investigated the association between skeletal muscle index (SMI) and hepatic steatosis in patients with T2DM. Methods: In this cross-sectional study, a total of 5,394 patients (2,718 men and 2,676 women) with T2DM were recruited from the outpatient clinic of Huh’s Diabetes Center from 2003 to 2016. Those patients who had a history of viral or other liver diseases or had alcohol consumption ≥140 g/week were excluded from the study. Skeletal muscle mass was estimated from bioimpedance analysis measurements and skeletal muscle mass index (SMI, %) was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. NAFLD was defined as the presence of hepatic steatosis on ultrasonography. Results: Thirty-six percent of men and 38% of women had NAFLD. Those with NAFLD had higher body mass index (BMI), waist circumference (WC), HbA1c, total cholesterol, triglyceride and blood pressure and lower HDL-cholesterol. SMI was lower in those with NAFLD (44.7 ± 8.1 vs. 45.7 ± 8.6%, p&amp;lt;0.001 in men and 37.6 ± 8.3 vs. 38.7 ± 8.9%, p=0.002 in women). Lower SMI tertiles were independently associated with higher prevalence of NAFLD (Ptrend&amp;lt;0.001). Odds ratio for NAFLD was 1.72 (95% confidence interval [CI] 1.25-2.37; p = 0.001) in patients with lowest SMI tertile compared with highest tertile after adjusting for possible confounding factors. Conclusion: Low skeletal muscle mass is independently associated with NAFLD in patients with T2DM. These findings suggest that sarcopenia is a risk factor for NAFLD in patients with T2DM. Disclosure D. Seo: None. M. Jung: None. S. Ahn: None. S. Hong: None. M. Nam: None. Y. Lee: None. Y. Choi: None. B. Huh: None. K. Huh: None. S. Kim: None. Funding National Research Foundation of Korea (2017R1D-1A1B03034581)

From the Editor’s desk…: June 2019

From the Editor’s desk…: June 2019

SAT-110 Long-Term Impact of Gastric Bypass versus Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease: Retrospective Observations from Michigan Bariatric Surgery Cohort

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in obese patients. Bariatric surgery is highly effective for treatment of NAFLD. We have previously reported 4 and 5-year weight loss outcomes in patients who underwent bariatric surgery at Michigan Medicine from 2008 to 2013. The aim of this study was to assess the impact of weight loss surgery on persistence of NAFLD up to 5 years post-surgery. Retrospective data on weight, blood pressure, lipid panel, A1c, liver enzymes, NAFLD Fibrosis scores (NFS) and imaging were analyzed with respect to the type of surgery [sleeve gastrectomy (SG) or Roux-en Y gastric bypass (GB)] at baseline and yearly for 5 years. Patients were assessed for presence of underlying NAFLD based on liver biopsy, imaging, or clinical diagnosis (ICD-9 or 10 codes) prior to surgery. Persistent NAFLD was assessed based on presence of hepatic steatosis on abdominal imaging (ultrasound, CT or MRI) over follow-up. Follow up data were available on 221 patients with NAFLD at baseline (GB =128, SG=93); median age 47 years (IQR 40-54) with 73% females and a median BMI of 46.2 kg/m2 (IQR 41.2-52.4). Median BMI was higher in the SG group versus GB owing to the criteria for approval in 2008-2012 (48.1 kg/m2 vs. 45.3 kg/m2, p=0.01). Median NFS was higher in SG vs GB (0.04 vs -0.50, p =0.01). Only 38 patients (17.2%) had a liver biopsy, among which 25 (65.8%) showed non-alcoholic steatohepaitis (NASH) and 3 (7.9%) demonstrated cirrhosis. Both groups had a reduction in NFS over follow up with median NFS significantly lower at all-time points in the GB group, p<0.01); improvement in NFS was more pronounced in the GB group at year 1, p=0.03. Overall, 83 patients (37.5%) had follow-up abdominal imaging with 28 (33.7%) having evidence of persistent NAFLD; 28.7% at 1-2 years, 16.3% at 2-4 years, and 55% at >4 years post-surgery. The nadir of BMI occurred at 1 year (median 31.3 and 37.2, in BG versus SG, respectively), with a peak at year 4 for GB (median 35.6) and year 5 for SG (median 40.4). At all-time points, the median weight loss was highest in the GB group. All metabolic parameters remained improved compared to baseline. The following differences were noted in the GB group versus SG group: LDL was significantly lower at year 1, 2 and 5; cholesterol significantly lower at year 1 and 2; significantly larger reduction in hemoglobin A1c at year 2, 4 and 5; and reduction in TG significantly higher at year 1. In a multivariable model integrating type of surgery, baseline diabetes and baseline hyperlipidemia, baseline hyperlipidemia was independently associated with persistent NAFLD (OR: 3.2, 95% CI 1.04-10.10, p=0.04). Change in weight was not predictive of persistent NAFLD. In conclusion, these observations suggest that bariatric surgery may have a weight-independent effect on NAFLD. Further studies are needed to examine the effect of disease severity and co-morbidities on NAFLD resolution after bariatric surgery.

Accuracy of ultrasonography in the assessment of liver fat compared with MRI

To investigate the accuracy of ultrasonography in the assessment of hepatic steatosis using magnetic resonance imaging (MRI) as standard of reference and to explore the influence of additional hepatic iron overload. A total of 2,783 volunteers (1,442 women, 1,341 men; mean age, 52.3±13.8 years) underwent confounder-corrected chemical-shift-encoded MRI of the liver at 1.5 T. Proton-density fat fraction (PDFF) and transverse relaxation rate (R2*) were calculated to estimate hepatic steatosis and liver iron overload, respectively. In addition, the presence of hepatic steatosis was assessed by B-mode ultrasonography. The sensitivity, specificity, and accuracy of hepatic ultrasonography were determined for different degrees of hepatic steatosis and different amounts of liver iron. MRI revealed hepatic steatosis in 40% of participants (n=1,112), which was mild in 68.9% (n=766), moderate in 26.7% (n=297), and severe in 4.4% (n=49) of patients. Ultrasonography detected hepatic steatosis in 37.8% (n=1,052), corresponding to 74.5% sensitivity and 86.6% specificity. The sensitivity of ultrasound increased with the amount of hepatic fat present and was 65.1%, 95%, and 96% for low, moderate, and high fat content; whereas the specificity was constantly high at 86.6%. The diagnostic accuracy of ultrasound for detection of hepatic steatosis did not vary significantly with the amount of liver iron present. Ultrasonography is an excellent tool to assess hepatic steatosis in the clinical setting with some limitations in patients with a low liver fat content. The detection of hepatic steatosis by ultrasonography is not influenced by liver iron.

Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.

This study was conducted in order to evaluate if iso- or hyperintensity of HCAs on HBP is systematically related to a high uptake of hepatospecific contrast agent, using a quantitative approach. This bicentric retrospective study included all patients with histologically confirmed and subtyped HCA from 2009 to 2017 who underwent MRI with HBP after Gd-BOPTA injection and who showed iso- or hyperintensity on HBP. The signal intensity of tumors on pre- and postcontrast images and the presence of hepatic steatosis were noted. Contrast uptake on HBP was quantified using the liver-to-lesion contrast enhancement ratio (LLCER) and compared between HCA subtypes (Wilcoxon signed-rank test). Categorical variables were compared using chi-square tests. Twenty-four HCAs showed iso- or hyperintensity on HBP, specifically 17 inflammatory (IHCAs) and 7 β-catenin HCAs (BHCAs). Eighteen HCAs (75%) (17 IHCAs and 1 BHCAs) had a LLCER < 0% (median - 13.6%, group 1), of which 94% were hyperintense on precontrast T1-W images, with background hepatic steatosis. Six HCAs (25%) had LLCER ≥ 0% (median 2.9%, group 2), and all were BHCAs. A LLCER ≥ 1.6% was associated with the diagnosis of BHCA with a sensitivity of 86% and a specificity of 100%. In conclusion, iso- or hyperintensity of hepatocellular adenomas on HBP does not necessarily correspond to an increased hepatospecific contrast-agent uptake. In IHCA, tumor hyperintensity on precontrast images and the underlying steatosis likely explain such iso- or hyperintensity, which do show reduced HBP contrast-agent uptake. On the other hand, marked contrast uptake can be observed, especially in BHCA. • Iso- or hyperintensity on HBP does not necessarily reflect a high uptake of hepatospecific contrast agent. • Discrepancies between qualitative signal intensity and quantitative hepatospecific contrast uptake can be explained in IHCA by a combination of tumor hyperintensity on precontrast images and underlying hepatic steatosis. • In BHCA, iso- or hyperintensity on HBP does actually correspond to a greater contrast uptake than that of the liver, demonstrated by an increased lesion-to-liver contrast enhancement ratio (LLCER).

Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence

The presence of hepatic steatosis (HS) is an important histological feature in a variety of liver disease. It is critical to assess HS accurately, particularly where it plays an integral part in defining the disease. Conventional methods of quantifying HS remain semi-quantitative, with potential limitations in precision, accuracy and subjectivity. Second Harmonic Generation (SHG) microscopy is a novel technology using multiphoton imaging techniques with applicability in histological tissue assessment. Using an automated algorithm based on signature SHG parameters, we explored the utility and application of SHG for the diagnosis and quantification of HS. SHG microscopy analysis using GENESIS (HistoIndex, Singapore) was applied on 86 archived liver biopsy samples. Reliability was correlated with 3 liver histopathologists. Data analysis was performed using SPSS. There was minimal inter-observer variability between the 3 liver histopathologists, with an intraclass correlation of 0.92 (95% CI 0.89–0.95; p < 0.001). Good correlation was observed between the histopathologists and automated SHG microscopy assessment of HS with Pearson correlation of 0.93: p < 0.001. SHG microscopy provides a valuable tool for objective, more precise measure of HS using an automated approach. Our study reflects proof of concept evidence for potential future refinement to current conventional histological assessment.

Utility of different indices in screening Chinese postmenopausal women for hepatic steatosis.

To analyze the potential of fatty liver index (FLI) and several obesity indices and to explore which index is best for predicting nonalcoholic fatty liver disease (NAFLD) in Chinese postmenopausal women. A cross-sectional study was conducted in 680 Chinese postmenopausal women. NAFLD was defined as a hepatic steatosis observed on liver ultrasonography in the absence of a second cause. Odds ratio and corresponding 95% confidence interval (CI) between hepatic steatosis and FLI as well as different obesity indices were evaluated by Binary Logistic regression model. Receiver operating characteristic curve and area under curve (AUC) were used to compare the ability of predicting hepatic steatosis between FLI and obesity indices. The upper values of all indices were significantly associated with the presence of hepatic steatosis (all p<0.01) after the adjustment for potential confounders. The largest AUC [0.85 (0.82-0.88), 95% CI, p<0.01] was observed for FLI, followed by the frequently used obesity indices. FLI is closely associated with the presence of hepatic steatosis in Chinese postmenopausal women. Compared to the obesity indices frequently used, FLI is a better surrogate marker for predicting the presence of hepatic steatosis in Chinese postmenopausal women.

Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy.

IntroductionNon‐alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver‐related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource‐limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono‐infection under long‐term antiretroviral therapy (ART) in Rio de Janeiro, Brazil.MethodsClinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross‐sectional study (PROSPEC‐HIV study; NCT02542020). Patients with viral hepatitis co‐infection, ART‐naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed.ResultsIn total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2, alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features.ConclusionIntegrated strategies for preventing non‐communicable diseases in people with HIV mono‐infection are necessary to decrease the burden of liver diseases.Clinical Trial Number: NCT02542020.

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease.

The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). Retrospective analysis of prospectively acquired data. Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. 1.5T and 3T; chemical-shift encoded multiecho gradient echo. Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*. Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method. Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456-1466.

Hepatic Steatosis Is Highly Prevalent but Is Not Correlated With Advanced Fibrosis in Autoimmune Hepatitis: Results Obtained at the Autoimmune Hepatitis Association National Meeting

Introduction: Obesity and associated steatosis are unfavorable prognostic factors in viral hepatitis. A recent report suggested that coexisting fatty liver disease may adversely affect the natural history of patients with autoimmune hepatitis in a similar fashion. We conducted a study to examine the prevalence of hepatic steatosis in individuals with autoimmune hepatitis. Methods: Vibration-controlled transient elastography (Fibroscan) was offered to patients with autoimmune hepatitis (AIH) at the Autoimmune Hepatitis Association (AIHA) national meeting in June 2017 in Indianapolis. All participants were fasting for 3 hours prior to examination. Based on the NASH CRN criteria for 90% sensitivity, presence of hepatic steatosis was defined as Continuous Attenuation Parameter (CAP) ≥ 263 dB/m and severe hepatic steatosis as CAP score ≥ 274 dB/m. The presence of compensated advanced chronic liver disease (cACLD) was defined as: liver stiffness measurement (LSM) > 15 kPa as highly suggestive, 10-15 kPa) as suggestive and < 10 kPa as unlikely. Results: 221 participants attended the AIHA conference in which 148 (67%) carried the diagnosis of AIH and 73 (33%) were caregivers. In total, 74 (50%) participants with AIH (8% male and 92% female) completed Fibroscan examination. This group had a median age of 48 years (yrs) and BMI 29 kg/m2. The median liver stiffness and CAP scores of all participants was 6.8 kPa and 236 dB/m, respectively. 22 (30%) patients had steatosis whereas 19 (26%) severe steatosis. Individuals with both steatosis and severe steatosis had higher BMI (32.6 kg/m2, 32.9 kg/m2) compared to those without steatosis (26.8 kg/m2, p=0.01). Patients with steatosis (50 yrs) also tended to be older compared to those without steatosis (47 yrs, p=0.09). According to the parameters of cACLD, 11 (15%) individuals were highly suggestive, 12 (16%) were suggestive, and 51 (69%) had no evidence of cACLD. Advanced fibrosis was more likely in participants that were male (67% vs 28%, p=0.07) and had higher BMI (31 kg/m2 vs 27.1 kg/m2, p=0.02). There was no significant correlation between advanced fibrosis and the presence of steatosis (r=0.17, p=0.3) or severe steatosis (r=0.18, p=0.3). Conclusion: In patients with AIH there is high prevalence of any steatosis or severe steatosis, but lack of their correlation with advanced fibrosis argues against a role for steatosis in worsening fibrosis in patients with AIH.946_C Figure 3. Liver Cancer Death Rate946_B Figure 2. GI Fellowships

The impact of diet-induced hepatic steatosis in a murine model of hepatic ischemia/reperfusion injury.

The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade, and end-stage liver disease secondary to nonalcoholic steatohepatitis has become 1 of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. Although in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia/reperfusion injury (IRI) and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers. However, it remains controversial whether steatotic livers can be safely used for transplantation and how best to improve the performance of steatotic grafts. We aimed to evaluate the impact of diet-induced hepatic steatosis in a murine model of IRI. Using a diet of high trans-fat, fructose, and cholesterol (HTF-C) and a diet high in saturated fats, sucrose, and cholesterol (Western diet), we were able to establish models of mixed macrovesicular and microvesicular steatosis (HTF-C) and microvesicular steatosis (Western). We found that the presence of hepatic steatosis, whether it is predominantly macrovesicular or microvesicular, significantly worsens IRI as measured by plasma alanine aminotransferase levels and inflammatory cytokine concentration, and histological evaluation for necrosis. Additionally, we report on a novel finding in which hepatic IRI in the setting of steatosis results in the induction of the necroptosis factors, receptor interacting protein kinase (RIPK) 3, RIPK1, and mixed-lineage kinase domain-like. These data lay the groundwork for additional experimentation to test potential therapeutic approaches to limit IRI in steatotic livers by using a genetically tractable system. Liver Transplantation 24 908-921 2018 AASLD.

Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes.

Non-alcoholic steatohepatitis (NASH) is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, and hepatocyte injury with or without fibrosis. In this study, we explored the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor, on the progression of steatohepatitis in a murine model of NASH with diabetes. A novel NASH model with diabetes was generated by administration of streptozotocin injection to neonatal C57BL/6 mice (2-3daysold) combined with a high-fat diet feeding from the age of 4weeks. The plasma biochemical parameters, oxidative stress, inflammation and histopathological changes were assessed. APD668 alone showed reduction in plasma glucose (- 39%, P < 0.05) and triglyceride level (- 26%) whereas a combined treatment of APD668 with linagliptin resulted in a more pronounced reduction in plasma glucose (- 52%, P < 0.001) and triglyceride (- 50%, P < 0.05) in NASH mice. In addition, co-administration of APD668 with linagliptin demonstrated a significant decrease in hepatic triglyceride, NAS score, hepatic TBARS and hepatic TNF-α in NASH mice with diabetes. These findings suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of NASH.

Evaluation of Hepatic Steatosis and Fibrosis Using Transient Elastography in Partial Lipodystrophy Patients

Introduction: Partial lipodystrophy (PL) is a rare disease associated with insulin resistance and metabolic dysfunctions, including NAFLD. Global prevalence of NAFLD is ±25%. In PL patients NAFDL prevalence and severity remains unclear. AIMS To evaluate the presence of hepatic steatosis and/or fibrosis in PL patients using transient elastography (TE) in comparison to a control group. Materials and Methods: Fifteen patients (7 with PL of the limbs, 8 with Familiar Partial Lipodystrophy Dunnigan-type) and 15 (13 women) controls paired to BMI and age were included. We recruited participants aged 18-65 years-old and a BMI≥25 and ≤35kg/m², excluding other causes of steatohepatitis. Anthropometric measures, metabolic parameters and the presence of steatosis/fibrosis using TE(Fibroscan®) were evaluated. According to literature, the adopted cut-off values in TE for Controlled Attenuation Parameter (CAP) and Liver Stiffness Measurement (LSM) are ≥238dB/m and ≥5,8kPa, respectively. Student t-test was used for continuous variables. Main results are presented as Mean ± SD. Results: Mean age was 52.93 and 50.26 years-old in PL and control groups, respectively. BMI was slightly but not significantly higher in control group (30,13kg/m² [SD±2,85] vs. 27,43kg/m² [SD±5,30]). Waist-to-hip ratio did not differ. PL group had higher fasting plasma glucose (116.78mg/dL [SD±39,54] vs. 89,58mg/dL [SD±23,34], p= 0,0476). No differences in hepatic lesion biomarkers or lipid profile was noted, except for a lower HDL-c in PL group (40,64mg/dL [SD±9,45] vs. 49,62mg/dL [SD±12,67], p=0,0432). CAP tended to be higher in PL patients [301,82dB/m (SD±54,88) vs. 262,93dB/m (SD±57,44); p=0,0685] and LSM was significantly higher (7,32kPa [SD±3,71] vs. 4,94kPa [SD±1,58], p=0,0260). Conclusions: Patients with PL presented a trend for increased hepatic steatosis and showed higher values of fibrosis in TE. Therefore, we suggest PL patients should undergo TE for screening of NAFLD. Disclosure L.C. Viola: None. F.O. Matsuura: None. C.M. Valerio: None. A.F. Godoy-Matos: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Other Relationship; Self; Takeda Development Center Americas, Inc., Novo Nordisk Inc.. M.H. Costa: None. J.M. Araujo-Neto: None. M. Dias: None.

Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Metabolic syndrome (MS) components are highly prevalent in NAFLD. Our aim is to assess the relationship of NAFLD and MS with long-term outcome of mortality.The Third National Health and Nutrition Examination Survey (NHANES) was utilized. NAFLD was diagnosed by ultrasound in the presence of hepatic steatosis and no other causes of chronic liver disease. History of MS and its components were obtained from self-reported NHANES questionnaires. Mortality was obtained from Mortality-Linkage File, through December 31, 2011. Chi-square test was used for categorical variables and Cox proportional models estimated hazard ratios with 95% confidence interval.NAFLD cohort (n = 3613) had a median age of 43 years, 73% white, and 50% male. NAFLD group with at least one MS condition was significantly older, had higher body mass index, more likely to have insulin resistance, and heart disease compared to NAFLD group without MS. Over 19-years of follow-up, 1039 people died. Compared to NAFLD patients without MS, presence of one MS component increased the risk of mortality at 8-year (2.6% vs 4.7%) and 16-year (6% vs 11.9%) (P < .001). After adjusting for socio-demographic factors, NAFLD with all MS components was associated with overall, cardiac and liver-mortality. Increased number of MS components was associated with lower survival (P < .0001).Patients with NAFLD and MS have higher mortality risk compared to NAFLD patients without MS. These NAFLD patients should be prioritized for the development of treatment regimens.