Presence Of Liver Steatosis Research Articles

Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients with Inflammatory Bowel Diseases: A Pilot Study.

Inflammatory bowel disease (IBD) is characterized by persistent inflammation and is often associated with metabolic dysfunction-associated steatotic liver disease (MASLD). IBD patients are at risk of developing MASLD due to shared risk factors such as gut dysbiosis and systemic inflammation. The new MASLD nomenclature emphasizes the link between liver steatosis and cardiometabolic comorbidities. However, the prevalence of MASLD in IBD patients remains poorly explored. The main aim of this cross-sectional study is to assess the prevalence of ultrasound (US) and the clinical features of MASLD in patients with IBDs. We conducted a retrospective study enrolling 272 Italian IBD patients attending Renato Dulbecco Teaching Hospital in a period between 1 January 2021 and 31 December 2023. MASLD was diagnosed based on the presence of liver steatosis with cardiometabolic risk factors, using established guidelines. Demographic, clinical, and laboratory data were collected and analyzed. Statistical significance was determined at a p-value < 0.05. Of the 272 IBD patients, 6% had non-alcoholic fatty liver disease (NAFLD), while 18% had MASLD. Patients with IBD-MASLD were significantly older, had higher body mass index, waist circumference, and triglyceride levels, and were more likely to have type 2 diabetes mellitus and hypertension compared to those with IBD-NAFLD. IBD-MASLD patients also showed higher disease activity scores and required more frequent surgical interventions. Bivariate logistic regression revealed triglyceride levels as a significant predictor of MASLD in IBD patients. MASLD is more prevalent in IBD patients, highlighting the importance of early detection of liver steatosis in this at-risk population. The association between MASLD and cardiometabolic risk factors underscores the need for a multidisciplinary approach to manage these patients effectively. Further studies in larger cohorts are necessary to confirm these findings and explore the pathophysiological mechanisms involved.

Abstract 14: Arterial Stiffness in Obese Normotensive Children: The First Cardiovascular Risk Biomarker?

Introduction: Obesity is an emerging pandemic driven by consumption of a diet rich in fat, highly refined carbohydrates and a sedentary lifestyle in both children and adults. In obesity arterial stiffness (AS) often associated with endotelial dysfunction (ED) is an independent and strong predictor of cardiovascular disease (CVD) and is a precursor to atherosclerosis, systolic hypertension, cardiac diastolic dysfunction, and impairment of coronary and cerebral flow. In obese children, AS also promotes fatty liver disease whitch eventually leads to fibrosis. Aim of Study: In obese children (OC), central blood pressuere, arterial stiffness and endothelial dysfunction, liver steatosis/fibrosis were evaluated and compared with control group (CG), non-obese, non-hypertensive children. Methods: Carotid-femoral pulse wave velocity (PWV) is the current non-invasive method of choice to asses AS and PWV carotid-brachial variation pre- and post-induced transient ischemia of brachial artery to evaluate ED. Fibroscan (FS) and Control Attenuation Parameter (CAP) are a non-invasive reliable examination that allows to know the degree of liver steatosis and liver stiffness (fibrosis). Carotid-femoral PWV (AS) and PWV variation of brachial artery (ED) were assessed using Complior System® (Artech-Medical France). We evaluated 31 obese children between 10 and 13 years old (BMI 28.70±3.72) and compared to CG (between 11 and 13 years old, n=16, BMI 19.89±1.75) Results: In obese children (BMI 28.70±3.72 and Z score 2.02±0.42) vs CG (BMI 19.89±0.75 and Z core 0.57±0.24), PWV-CF (arterial stiffness) was significantly increased: 5.8±1.3 m/s vs. 3.4±0.9 m/s, p&lt;0.01. PWV-CB variation were paradogical (endothelial dysfunction) after transient ischemia in obese children (△+9% compared to baseline) and it was as epected in the CG (△-12.2% compared to baseline) (P&lt;0.001). Fibroscan and CAP revealed that the degree of steatosis was significantly higher in OC but no differences were found in the degree of liver fibrosis. Conclusions: We found a significatly increase in arterial stiffness in obese children compared to CG. Arterial stiffness in obese children often precedes the development of hypertension and liver fibrosis (even in the presence of liver steatosis) suggesting that arterial stiffness is one of the earliest biomarkers for increased cardiovascular risk. Interventions aimed at attenuating obesity in chidhood are emerging as important target to improve public health outcomes.

Combined impact of myosteatosis and liver steatosis on prognosis in stage I-III colorectal cancer patients.

Myosteatosis and liver steatosis (LS) have been recognized as patient-derived image biomarkers that correlate with prognosis in colorectal cancer (CRC) patients. However, the significance of considering fat deposition in multiple body areas simultaneously has been underestimated. This study aimed to investigate the combined effect of myosteatosis and LS in stage I-III CRC patients. A total of 616 stage I-III CRC patients were included in the study. Myosteatosis was assessed using skeletal muscle radiodensity (SMD), and LS was estimated by calculating the Hounsfield unit of the liver and spleen ratio (LSR). Cox proportional hazard models were utilized to evaluate disease-free survival (DFS). A combination of myosteatosis and LS was proposed, and its discriminatory performance was compared using the C-index. Among the 616 participants, the median (interquartile) age was 64 (55-72) years, and 240 (38.9%) were female. The median and interquartile range of LSR were determined as 1.106 (0.967-1.225). The optimal cutoff value for LSR was identified as 1.181, leading to the classification of patients into low (410, 66.5%) and high LSR (206, 33.4%) groups. Among the patients, 200 were categorized into the low SMD group, while 416 were allocated to the high SMD group. Both myosteatosis and LS were identified as independent prognostic factors in the multivariable analysis. The combination of these two variables resulted in a three-group classification: high SMD with low LSR group, high SMD with high LSR group, and low SMD group. When comparing the C-index values, the three-group classification exhibited superior discriminatory performance compared with considering myosteatosis and LS separately. Myosteatosis was associated with poorer survival, while the presence of LS was linked to a better prognosis in non-metastatic CRC patients. Simultaneously considering fat infiltration can serve as a more effective prognosticator in non-metastatic CRC patients.

AI-based CT Body Composition Identifies Myosteatosis as Key Mortality Predictor in Asymptomatic Adults.

Background Body composition data have been limited to adults with disease or older age. The prognostic impact in otherwise asymptomatic adults is unclear. Purpose To use artificial intelligence-based body composition metrics from routine abdominal CT scans in asymptomatic adults to clarify the association between obesity, liver steatosis, myopenia, and myosteatosis and the risk of mortality. Materials and Methods In this retrospective single-center study, consecutive adult outpatients undergoing routine colorectal cancer screening from April 2004 to December 2016 were included. Using a U-Net algorithm, the following body composition metrics were extracted from low-dose, noncontrast, supine multidetector abdominal CT scans: total muscle area, muscle density, subcutaneous and visceral fat area, and volumetric liver density. Abnormal body composition was defined by the presence of liver steatosis, obesity, muscle fatty infiltration (myosteatosis), and/or low muscle mass (myopenia). The incidence of death and major adverse cardiovascular events were recorded during a median follow-up of 8.8 years. Multivariable analyses were performed accounting for age, sex, smoking status, myosteatosis, liver steatosis, myopenia, type 2 diabetes, obesity, visceral fat, and history of cardiovascular events. Results Overall, 8982 consecutive outpatients (mean age, 57 years ± 8 [SD]; 5008 female, 3974 male) were included. Abnormal body composition was found in 86% (434 of 507) of patients who died during follow-up. Myosteatosis was found in 278 of 507 patients (55%) who died (15.5% absolute risk at 10 years). Myosteatosis, obesity, liver steatosis, and myopenia were associated with increased mortality risk (hazard ratio [HR]: 4.33 [95% CI: 3.63, 5.16], 1.27 [95% CI: 1.06, 1.53], 1.86 [95% CI: 1.56, 2.21], and 1.75 [95% CI: 1.43, 2.14], respectively). In 8303 patients (excluding 679 patients without complete data), after multivariable adjustment, myosteatosis remained associated with increased mortality risk (HR, 1.89 [95% CI: 1.52, 2.35]; P < .001). Conclusion Artificial intelligence-based profiling of body composition from routine abdominal CT scans identified myosteatosis as a key predictor of mortality risk in asymptomatic adults. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tong and Magudia in this issue.

Monte Carlo modeling of hepatic steatosis based on stereology and spatial distribution of fat droplets

Background and ObjectiveTo model hepatic steatosis in adult humans with non-alcoholic fatty liver disease based on stereology and spatial distribution of fat droplets from liver biopsy specimens. MethodsHistological analysis was performed on 30 adult human liver biopsy specimens with varying degrees of steatosis. Morphological features of fat droplets were characterized by gamma distribution function (GDF) in both two-dimensional (2D) and three-dimensional (3D) spaces from three aspects: 1) size distribution indicating non-uniformity of fat droplets in radius; 2) nearest neighbor distance distribution indicating heterogeneous accumulation (i.e., clustering) of fat droplets; 3) regional anisotropy indicating inter-regional variability in fat fraction (FF). To generalize the morphological description of hepatic steatosis to different FFs, correlation analysis was performed among the estimated GDF parameters and FFs for all specimens. Finally, Monte Carlo modeling of hepatic steatosis was developed to simulate fat droplet distribution in tissue. ResultsMorphological features, including size and nearest neighbor distance in 2D and 3D spaces as well as regional anisotropy, statistically captured the distribution of fat droplets by the GDF fit (R2 > 0.54). The estimated GDF parameters (i.e., scale and shape parameters) and FFs were well correlated, with R2 > 0.55. In addition, simulated 3D liver morphological models demonstrated similar sections to real histological samples both visually and quantitatively. ConclusionsThe morphology of hepatic steatosis is well characterized by stereology and spatial distribution of fat droplets. Simulated models demonstrate similar appearances to real histological samples. Furthermore, the model may help understand MRI signal behavior in the presence of liver steatosis.

Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Screening for Liver Steatosis and Fibrosis in Patients with Inflammatory Bowel Disease Using Vibration Controlled Transient Elastography with Controlled Attenuation Parameter.

Background and Aims: Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, hepatic injury being of concern in these patients. Current literature reports an increased prevalence of liver steatosis and fibrosis in subjects with IBD and the pathophysiology is yet to be completely understood. The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with IBD, as well as to determine the factors that connect these two disorders. Methods: From September 2021 to June 2022, 82 consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter (CAP) was used to assess the presence of NAFLD, with a cut-off score for CAP of 248 dB/m. Significant liver fibrosis was considered at a cut-off for liver stiffness measurements (LSM) of 7.2 kPa. Results: In total, 82 IBD patients (54.8% men, mean age of 49 ± 13 years) were included, 38 (46.3%) of them being diagnosed with NAFLD, with a mean CAP score of 286 ± 35.4 vs. 203 ± 29.7 in patients with IBD only. Age (β = 0.357, p = 0.021), body mass index (BMI) (β = 0.185, p = 0.048), disease duration (β = 0.297, p = 0.041), C—reactive protein (β = 0.321, p = 0.013), fasting plasma glucose (β = 0.269, p = 0.038), and triglycerides (β = 0.273, p = 0.023) were strongly associated with the presence of liver steatosis. The multivariate analysis showed that older age, BMI, and disease duration were strongly associated with significant liver fibrosis in our group. Conclusions: NAFLD is a multifaced pathology with growing prevalence among IBD patients. Additional studies are needed to completely understand this problem and to create a solid evidence-based framework for more effective preventative and intervention strategies.

Noninvasive biomarkers of non-alcoholic fatty liver disease in patients with metabolic syndrome: insights from the RESOLVE Study.

The aim of the present study was to evaluate: 1) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from metabolic syndrome (MS); and 2) the association of FLI, HSI and LFS with the cardiometabolic risks. A total of 91 patients with MS (39 men, 52 women) and 44-age matched healthy subjects (control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis. Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (P<0.05). Also, FLI and LFS were positively associated with MetsScore (P<0.01 and P<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (P<0.001). FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

Effect of liver steatosis on liver stiffness measurement in chronic hepatitis B patients with normal serum alanine aminotransferase levels: A multicentre cohort study.

Liver steatosis is becoming increasingly common in patients with chronic hepatitis B (CHB), and its effect on liver stiffness measurement (LSM), as assessed by transient elastography, remains controversial. Seven hundred and fifty-five patients with CHB and normal serum alanine aminotransferase levels, who underwent vibration-controlled transient elastography and liver biopsy, were included in the study. We examined whether the histological degree of liver steatosis affects the accuracy of transient elastography-assessed LSM in these patients. Among the 755 CHB patients included in the study, 286 (37.9%) had liver steatosis, of whom 156had grade S1, 74had grade S2, and 56had grade S3 on histology. Presence of liver steatosis was independently associated with greater body mass index (BMI, adjusted-odds ratio [OR]=5.786, 95% CI: 3.998-8.373, p=0.018), and higher serum total cholesterol (adjusted-OR=7.944, 95% CI: 4.731-13.339, p<0.001) and triglyceride levels (adjusted-OR=2.777, 95% CI: 2.050-3.761, p<0.001). There was no significant association between liver steatosis and fibrosis stage (OR=1.016, 95% CI: 0.905-1.140, p=0.790). Age (B-coefficient = 0.020, 95% CI: 0.001-0.040, p=0.044), BMI (B-coefficient=0.060, 95% CI: 0.011-0.127, p=0.019), serum gamma-glutamyl-transpeptidase (GGT, B-coefficient=0.015, 95% CI: 0.001-0.029, p=0.032), positivity for HBeAg (B-coefficient=-0.816, 95% CI: -1.568 to -0.064, p=0.034), as well as liver fibrosis stage (B-coefficient=2.796, 95% CI: 2.501-3.090, p<0.001), and inflammation activity grade (B-coefficient=0.648, 95% CI: 0.162-1.135, p=0.009) were all independently associated with higher LSM, while no significant association was found between degree of liver steatosis and LSM. Among patients with the same histological fibrosis stage, LSM values did not show any significant difference among patients with absent, mild, moderate or severe steatosis. We conclude that liver steatosis has no significant effect on transient elastography-measured LSM in CHB patients with normal serum alanine aminotransferase levels.

Ассоциация синдрома избыточного бактериального роста и неалкогольной жировой болезни печени у детей

Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) занимает лидирующие позиции среди хронических заболеваний печени у детей в промышленно развитых странах. Известно, что для пациентов с НАЖБП характерна высокая распространенность синдрома избыточного бактериального роста (СИБР). Цель работы — изучить влияние СИБР на структурно-функциональные показатели печени у детей с избыточным весом и ожирением. Материалы и методы. Обследовано 73 ребенка в возрасте от 6 до 17 лет, средний возраст пациентов составил (11,41 ± 2,68) года. В зависимости от наличия избыточного веса/ожирения и результатов водородного дыхательного теста (ВДТ) с глюкозой пациенты были разделены на 2 группы: 1 группа — 30 детей с избыточным весом/ожирением и наличием СИБР, 2 группа — 28 детей с избыточным весом/ожирением без СИБР. Контрольную группу составили 15 практически здоровых детей с нормальным весом и без СИБР по результатам ВДТ с глюкозой. Наличие стеатоза печени устанавливали при помощи транзиентной эластографии с функцией САР. Дополнительно проводили ВДТ с лактозой и биохимический анализ крови с определением показателей биохимической гепатограммы, липидного и углеводного спектров. Результаты. Установлено, что 70 % детей 1 группы имели сопутствующую НАЖБП по сравнению с 32 % во 2 группе. В 1 группе скорость оседания эритроцитов была выше, чем во 2 и 3 группах (p &lt; 0,05). Также у детей 1 группы уровни триглицеридов и липопротеинов очень низкой плотности были в 1,5 раза выше. Отмечена тенденция к более высоким значениям инсулина и индекса НОМА в 1 группе по сравнению со второй. Мальабсорбция лактозы диагностирована у 17 (56,7 %) детей с НАЖБП, лактозозависимый СИБР — у 15 (50,0 %). При ожирении без НАЖБП мальабсорбция лактозы выявлена у 10 (35,7 %) пациентов, а лактозозависимый СИБР — у 9 (32,1 %). Таким образом, у детей с НАЖБП мальабсорбция лактозы встречалась в 1,6 раза чаще, чем у детей без НАЖБП. Выводы. Установлено, что НАЖБП является фактором риска формирования СИБР. СИБР ассоциирован с низкоуровневым воспалением, дети с СИБР на фоне ожирения характеризовались более неблагоприятным метаболическим профилем в виде изменений параметров липидного и углеводного обмена, что может приводить к прогрессированию НАЖБП. Продемонстрирована высокая частота мальабсорбции лактозы и лактозозависимого СИБР у детей с НАЖБП.

The needs of surveillance of metabolic associated fatty liver disease in Taiwan

The needs of surveillance of metabolic associated fatty liver disease in Taiwan

Vitamin D deficiency in patients with chronic intestinal failure on home parenteral nutrition.

Vitamin D deficiency is an important complication of chronic intestinal failure (CIF). Liver steatosis is a known late complication of long-term home parenteral nutrition (HPN) therapy in patients with CIF, which can progress to intestinal failure-associated liver disease (IFALD). The aim of this study was to determine the prevalence of vitamin D deficiency among Slovene HPN patients and determine any potential correlation between serum vitamin D levels and liver steatosis associated with IFALD in adult patients with CIF on HPN therapy. Adult patients, diagnosed with CIF, receiving long term HPN therapy, were included in a cross-sectional study. Vitamin D status was determined by measuring serum levels of 25-hydroxyvitamin D. The presence of liver steatosis was diagnosed using 3TS MRI scanner. The association between serum vitamin D levels and liver steatosis was calculated using univariate logistic regression. We included 63 adult patients with CIF on HPN therapy in the study. The median duration of HPN therapy was 70 weeks. The average serum concentration of 25-hydroxyvitamin D was 41.3nmol/l. Insufficient vitamin D levels were found in 45 (73%) patients. Liver steatosis was present in 18 (28.6%) patients. No statistically significant association between serum vitamin D levels and liver steatosis in the study population was found. The results of this study have shown a high prevalence of vitamin D deficiency in adult patients with CIF on HPN. We failed to demonstrate an association between serum vitamin D levels and the prevalence of liver steatosis.

Congenital disorders of glycosylation in children – Histopathological and ultrastructural changes in the liver

Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and their attachment to proteins and lipids. Histologically, liver steatosis, fibrosis and cirrhosis have been reported in CDG. The aim of the study was to characterize the histopathological and ultrastructural liver changes in CDG patients hospitalized in our Institute, and to find the most characteristic features, as articles concerning the liver microscopic features in CDG are sparse. Out of 32 CDG patients diagnosed and followed-up in our Institute, the liver biopsy was performed in 4 of them, including 2 with MPI-CDG, 1 with SRD5A3-CDG, and 1 with PGM1-CDG, as a part of diagnostic process. In one patient, diagnosed post mortem with PMM2-CDG, the histopathological study comprised liver autopsy samples. The most common histopathological liver finding was the presence of steatosis (4/5) of varying severity, the mixed macro- and microvesicular type as well as the foamy degeneration of hepatocytes. In two patients, liver steatosis was associated with fibrosis, stage 4 (cirrhosis) and 2 according to Batts and Ludwig classification, respectively. In two patients, besides steatosis, mild inflammatory infiltrates composed of lymphoid cells in portal tracts were observed. No correlation between the patient's age and histopathological features was observed. The histopathological changes in the liver of CDG patients are miscellaneous; thus, based on the microscopic examination only, we can not identify (even suspect) the exact CDG. The most common histopathologic finding in our cohort of CDG patients was the presence of liver steatosis (of various severity) and foamy degeneration of hepatocytes.

Liver fibrosis in patients with metabolic associated fatty liver disease is a risk factor for adverse outcomes in COVID-19

BackgroundMetabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AimsTo evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. MethodsRetrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. Results432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. ConclusionThe presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.

Lack of awareness of liver organ damage in patients with type 2 diabetes

AimsLiver steatosis, a typical finding in patients with type 2 diabetes (T2D), can lead to cirrhosis and hepatocellular carcinoma. The aim of the present study is to estimate the awareness of liver disease among patients with T2D and whether it differs according to the degree of liver fibrosis estimated by transient elastography (TE).MethodsThis is a population-based cross-sectional study. We included all patients with T2D that participated in the 2017–2018 cycle of the National Health and Nutrition Examination Survey and underwent a TE examination. Presence of liver steatosis and fibrosis was assessed by the median values of controlled attenuation parameter and liver stiffness measurement, respectively.ResultsAmong the 825 patients included in the analysis, 8.1% (95% CI 5.1%-12.7%) of patients with steatosis were aware of having a liver condition. Even if awareness increased proportionally with increasing severity of organ damage, it remained limited even among patients with advanced fibrosis (17.9%, 95% CI 8.8%-33.3%).ConclusionsDespite increasing evidence of a frequent hepatic involvement associated with poor prognosis, awareness of suffering of advanced liver disease in patients with T2D is remarkably low, likely reflecting little recognition also among the team of health care professionals.

Presence of Liver Steatosis Is Associated With Greater Diabetes Remission After Gastric Bypass Surgery.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and β-cell dysfunction. Ectopic fat accumulation in liver and muscle causes IR. Since bariatric and metabolic surgery significantly improves fatty liver disease, we hypothesized that coexistence of liver steatosis (i.e., when hepatic IR contributes in T2DM) would be associated with greater diabetes improvement after surgery. A total of 519 patients with T2DM who underwent Roux-en-Y gastric bypass and simultaneous liver biopsy and had a minimum 5-year follow-up were analyzed to assess the independent association between biopsy-proven liver steatosis and postoperative long-term diabetes remission (glycated hemoglobin <6.5% [48 mmol/mol] off medications). Of the 407 patients with biopsy-proven liver steatosis, long-term diabetes remission was achieved in 211 (52%) patients compared with remission in 44 out of 112 (39%) patients without steatosis (P = 0.027). In multivariable analysis, presence of liver steatosis was an independent predictor of long-term diabetes remission (odds ratio 1.96 [95% CI 1.04-3.72]; P = 0.038). Hepatocyte ballooning, lobular inflammation, or fibrosis at baseline did not predict diabetes remission. This study, for the first time, suggests that in patients with T2DM who are considering bariatric and metabolic surgery, coexistence of liver steatosis is associated with better long-term glycemic outcomes. Furthermore, our data suggest that there are distinct variants of T2DM in which metabolic responses to surgical weight loss are different. A subgroup of patients whose T2DM is characterized by the presence of hepatic steatosis (presumably associated with worse IR) experience better postoperative metabolic outcomes.

Liver steatosis and nonalcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV.

The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association [nonalcoholic fatty liver disease (NAFLD) with fibrosis] to frailty as a measure of biological age in people living with HIV (PLWH). This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. Patients with hazardous alcohol intake and viral hepatitis coinfection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP ≥248 dB/m), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM at least 7.1 kPa. Frailty was assessed using a 36-Item frailty index. Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates. We analysed 707 PLWH (mean age 53.5 years, 76.2% men, median CD4 cell count 700 cells/μl, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9 and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment [odds ratio (OR) = 5.1, 1.6-15], vitamin D insufficiency (OR = 1.94, 1.2-3.2), obesity (OR = 8.1, 4.4-14.6), diabetes (OR = 3.2, 1.9-5.6), metabolic syndrome (OR = 2.41, 1.47-3.95) and osteoporosis (OR = 0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of frailty index included steatosis (OR = 2.1, 1.3-3.5), fibrosis (OR = 2, 1-3.7), NAFLD with fibrosis (OR = 9.2, 5.2-16.8), diabetes (OR = 1.7, 1-2.7) and multimorbidity (OR = 2.5, 1.5-4). Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.

Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis.

Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18–75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of ‘junk food’. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.

Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies.

Coexistence of alcohol use and metabolic risk-the 2 commonest population risk factors for nonviral chronic liver disease-is a growing concern. Clinical evidence and mechanistic evidence point to considerable supraadditive interaction effects for the development and progression of chronic liver disease between hazardous alcohol use and metabolic abnormalities including obesity, diabetes, and the metabolic syndrome (MetS). Intermittent binge drinking once monthly or more often seems to be associated with progression of liver disease even when average alcohol intake is within the currently allowed limits for a diagnosis of nonalcoholic fatty liver disease (NAFLD), and supraadditive interaction between binge drinking and the MetS has been reported. There are contradictory findings regarding the association between low alcohol use and liver steatosis, but, clearly, the mechanisms of alcoholic hepatotoxicity extend beyond simple fat accumulation. The presence of liver steatosis seems to amplify alcoholic hepatotoxicity. Recent longitudinal studies of NAFLD subjects report low alcohol use associated with both increased fibrosis progression and an elevated risk for liver cancer and severe liver disease. There is no clear safe limit of alcohol intake in the presence of NAFLD or metabolic risk. The interaction effects between alcohol and metabolic dysfunction merit increased attention in public health policy, individual counseling, and risk stratification. Based on current evidence, a strict dichotomization of liver disease into either pure alcoholic or nonalcoholic may be inappropriate.

A126 Presence of liver steatosis is associated with greater diabetes remission after gastric bypass surgery

A126 Presence of liver steatosis is associated with greater diabetes remission after gastric bypass surgery