Presence Of Hepatic Steatosis Research Articles

Hepatic Histopathology Among Excessive Drinkers Without Advanced Liver Disease.

Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis. We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase. Among 62 patients with aspartate aminotransferase (AST)≤50U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST>50U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells. Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.

Hepatic steatosis and hepatic iron overload modify the association of iron markers with glucose metabolism disorders and metabolic syndrome.

Iron status has been linked with impaired glucose metabolism (IGM), type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MetS), but the role of hepatic steatosis or iron overload on these associations remains uncertain. We analysed data from 2310 participants without known T2DM of the population-based Study of Health in Pomerania (SHIP-TREND, Germany) through logistic regression models. We tested additive and multiplicative interactions between ferritin and hepatic steatosis or iron overload. Serum ferritin was positively associated with IGM (OR per 100µg/L: 1.11 [1.01, 1.23]), T2DM (OR per 100µg/L: 1.20 [1.06, 1.36]) and MetS (OR per 100µg/L: 1.11 [1.02, 1.20]) in the total population as well as in participants without hepatic iron overload. However, the synergistic effect of higher ferritin concentrations and hepatic iron overload showed stronger associations with IGM and T2DM. Similarly, while ferritin was positively associated with T2DM and MetS even in the absence of hepatic steatosis, the synergistic effect of higher ferritin concentrations and hepatic steatosis showed stronger associations with IGM, T2DM and MetS. Transferrin was associated with isolated impaired glucose tolerance but not with T2DM and MetS. Our study suggests that ferritin may be associated with glucose metabolism disorders and MetS even in people without hepatic steatosis or iron overload. However, in individuals with higher ferritin concentrations, the presence of hepatic steatosis may indicate stronger risk for glucose metabolism disorders and MetS, while the presence of hepatic iron overload may indicate stronger risk only for glucose metabolism disorders.

Coronary artery disease and non-alcoholic fatty liver disease: Clinical correlation using computed tomography coronary calcium scans.

Background and AimNon‐alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored using coronary angiography, which showed a link between severe NAFLD and cardiovascular disease risk. This study's aim is to determine if computed tomography (CT) coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict the presence of NAFLD.MethodsThis was a retrospective cross‐sectional study of positive CT CAC scores and liver imaging with either CT; ultrasound; magnetic resonance imaging of the abdomen; or CT of the chest, which included liver images. Drinking 7 or 14 drinks per week for a female or male, respectively, and chronic viral hepatitis diagnosis were the exclusion criteria. CT CAC scores, hepatic steatosis, age, gender, lipid and liver panels, weight, blood pressure, F‐4/BARD scores, and hemoglobin A1c were correlated to CAD severity and NAFLD by logistic regression.ResultsA total of 134 patients with a mean age of 62.3 years (σ = 9.1), with 65% males, body mass index 28.5 (σ = 6.0), and 8% diabetics, were recruited. CAD severity was not associated with the presence of hepatic steatosis (odds ratio 1.96 [95% confidence interval, confidence interval 0.74–5.23] P = 0.36). Adjusted for variables, a link between hepatic steatosis, CAD severity, body mass index over 30 (odds ratio 6.77 [95% confidence interval 1.40–32.66] P = 0.02), and diabetes (odds ratio 9.60 [95% confidence interval 0.56–165.5] P = 0.01) was observed.ConclusionsIn patients with CAD detected using a positive CT CAC scan, we determined that BMI over 30 and diabetes were correlated with the presence of NAFLD. There was no direct relationship between CAD presence and hepatic steatosis presence.

Evaluation of clinical and imaging biomarkers for the prediction of new onset diabetes following pancreatic resection.

To identify clinical and imaging biomarkers that can predict the new onset of diabetes mellitus (NODM) within 1year of pancreatic resection. A retrospective chart review was conducted of 426 non-diabetic patients who underwent a pancreaticoduodenectomy or distal pancreatectomy at the University of Pittsburgh Medical Center between 2006 and 2016. Clinical characteristics and the patient's diabetic status at 1-year post resection were collected from the EMR. Imaging biomarkers included hepatic and pancreatic fat replacement, pancreatic calcifications, pancreatic duct diameter, pancreatic volume and body composition. Univariate and multivariable analyses were performed to demonstrate any predictive biomarkers of diabetes occurrence within 1year of pancreatic resection. 135/426 (31.7%) patients developed NODM. The only significant clinical predictor was older age (OR 1.02, 95% CI 1.002-1.039, p = 0.032). Imaging characteristics found to be significant included hepatic steatosis (OR 1.777, 95% CI 1.094-2.886, p = 0.02), larger reduction in pancreas volume (OR 0.989, 95% CI 0.979-0.999, p = 0.027), and greater preoperative visceral fat (OR 1.004, 95% CI 1.001-1.006, p = 0.001). Age, presence of hepatic steatosis, change in pancreatic volume, and preoperative visceral fat are independent predictive biomarkers for NODM following pancreatic resection.

Nonalcoholic Fatty Liver Disease and Recent Guideline Updates.

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Роль васкулоэндотелиального фактора роста в патогенезе стеатоза печени и дислипидемии

Цель исследования - изучение роли васкулоэндотелиального фактора роста в патогенезе неалкогольного стеатоза печени и дислипидемии при метаболическом синдроме. Методика. Обследовано 35 пациентов с неалкогольным стеатозом печени, в том числе 22 женщины и 13 мужчин. Группу контроля составили 12 сопоставимых по полу и возрасту лиц без патологии печени и признаков метаболического синдрома. Наличие жирового гепатоза подтверждали методом ультразвукового исследования. У пациентов с патологией печени рассчитывали индексы-предикторы стеатоза: Fatty Liver Index (FLI) и Hepatic Steatosis Index (HSI). У всех участников исследования определяли уровни провоспалительных цитокинов и васкулоэндотелиального фактора роста (ВЭФР), оценивали также липидный спектр крови и функциональные печеночные пробы. Результаты. У пациентов со стеатозом печени наблюдалось значимое увеличение уровней провоспалительных цитокинов, ВЭФР, общего холестерина и липопротеинов низкой и очень низкой плотности. Индекс атерогенности также был значимо выше, чем в контрольной группе. Концентрация ВЭФР положительно коррелировала с показателями окружности талии, тимоловой пробы, уровнями общего холестерина, липопротеинов низкой плотности и индексом атерогенности. Чувствительность FLI составила 91,4%, HSI - 97,1%. При этом, значения FLI и HSI значимо коррелировали с уровнем ВЭФР. Заключение. Полученные данные позволяют предположить, что ВЭФР, один из основных маркеров эндотелиальной дисфункции, может играть немаловажную роль в патогенезе неалкогольного стеатоза печени и дислипидемии у пациентов с метаболическомим синдромом The aim of the study was to assess the role of vascular endothelial growth factor (VEGF) in the pathogenesis of nonalcoholic hepatic steatosis and dyslipidemia in patients with signs of metabolic syndrome. Methods. 35 patients with nonalcoholic fatty liver disease, including 22 women and 13 men, were evaluated. The sex- and age-matched control group consisted of 12 people without liver pathology and metabolic syndrome criteria. Presence of hepatic steatosis was confirmed by an ultrasound examination. The Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI) were calculated for patients with hepatic steatosis. Concentrations of proinflammatory cytokines and VEGF were measured for all participants. Also, blood biochemistry, including the lipid profile and liver function tests, was analyzed. Results. In patients with hepatic steatosis, levels of proinflammatory cytokines and VEGF were significantly increased. Also, concentrations of total cholesterol, low-density lipoproteins, and very low-density lipoproteins were higher in patients with the liver pathology than in the control group. Atherogenic coefficient was increased in hepatic steatosis. Significant correlations were observed between VEGF and waist circumference, thymol test, total cholesterol, low-density lipoproteins, very low-density lipoproteins, and atherogenic coefficient. Sensitivity of FLI and HIS was 91.4% and 97.1%, respectively. Also, FLI significantly correlated with HSI and VEGF level. Conclusion. The study suggested that VEGF, of the main markers of endothelial dysfunction, plays an important role in the pathogenesis of nonalcoholic hepatic steatosis and dyslipidemia in patients with signs of metabolic syndrome.

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.

Abstract 14752: Hepatic Steatosis in Patients With the Fontan Circulation

Introduction: Hepatic steatosis is a leading cause of chronic liver disease, and it is most commonly attributed to nonalcoholic fatty liver disease (NAFLD). The interplay between hepatic steatosis and the development of liver disease following the Fontan procedure is not well understood. This study examined the prevalence and associations of hepatic steatosis in patients with a Fontan circulation. Methods and Results: This was a single-center retrospective study of 95 patients with a Fontan circulation who had a liver magnetic resonance imaging (MRI) performed between 2012 and 2019. Average age at MRI was 21.5 ± 8.5 years. Percent liver fat signal was determined using magnetic resonance chemical shift-encoded proton density fat fraction imaging. Hepatic steatosis was defined as liver fat greater than or equal to 5%; this was present in 10.5% of the population. The presence of hepatic steatosis was associated with higher body mass index (BMI) (29 ± 4 vs. 24 ± 6 kg/m 2 , p = 0.01), a higher frequency of obesity (50 vs. 12%, p = 0.02), lower high density lipoprotein (HDL) cholesterol (35 ± 9 vs. 43 ± 14 mg/dL, p = 0.05), and greater subcutaneous fat (2.6 ± 0.7 vs. 1.8 ± 1.0 cm, p = 0.04). Percent liver fat was positively associated with AST, triglyceride, and alkaline phosphatase levels. There was no association between hepatic steatosis and cardiovascular imaging or hemodynamic variables. Hepatic steatosis was not associated with the development of the composite outcome of: death, heart transplant, or escalation of diuretics (10 vs. 25%, p = 0.44). Conclusions: Risk factors for hepatic steatosis in patients with Fontan circulation are similar to the general population: obesity and dyslipidemia.

(13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle

Background & AimsNon-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear.MethodsWe used orally administered (13C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle.ResultsNAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes.ConclusionsThe interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases.Lay summaryObesity is progressively increasing worldwide and is paralleled by fat accumulation in the liver (non-alcoholic fatty liver disease [NAFLD]), the most common chronic liver disease worldwide. NAFLD can alter liver structure and function, with a variety of consequences ranging from asymptomatic and subclinical alterations to cirrhosis and cancer. (13C)-Methacetin breath test, a non-invasive diagnostic tool, can reveal early subclinical alterations of liver dynamic function in individuals with obesity and in patients with NAFLD.

Association Between Subclinical Left Ventricular Myocardial Systolic Dysfunction Detected by Strain and Strain‑Rate Imaging and Liver Steatosis and Fibrosis Detected by Elastography and Controlled Attenuation Parameter in Patients with Metabolic Syndrome.

PurposeThe components of metabolic syndrome (MS) are risk factors for developing both cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Strain (SI) and strain‑rate imaging (SRI) are able to recognize early changes in cardiac function. Vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) detect and quantify liver fibrosis and steatosis. We aimed to assess whether there is any correlation between liver fibrosis and steatosis and left ventricular (LV) dysfunction in MS patients.Patients and MethodsA total of 150 adults with MS were registered in the study. They were compared with a control group of 150 age- and sex-matched adults without MS. After the classic echocardiographic assessment of LV function, two-dimensional speckle echocardiography (2D-STE) was used to evaluate LV peak systolic strain (S) and peak systolic strain rate (SR), while liver steatosis and fibrosis were evaluated by VCTE and CAP.ResultsLV diastolic dysfunction was significantly more frequent among the patients with MS. We found significant differences between the two groups regarding the presence of subtle LV systolic dysfunction, detected by reduced values of S and SR. The risk for LV diastolic dysfunction was 3.6 times higher in MS with severe steatosis and 8 times higher in patients with severe fibrosis, P<0.0001. The risk for LV systolic dysfunction was double in MS with severe steatosis and 1.7 times higher in MS with severe fibrosis, P<0.0001.ConclusionIn MS patients with normal LV ejection fraction, conventional echocardiography parameters identified diastolic LV dysfunction, while SI and SRI identified subtle impairment of systolic LV dysfunction. The presence of hepatic steatosis and fibrosis increases significantly the risk for cardiac dysfunction in MS patients (P<0.0001).

A Cross Over Trial Evaluating Combined Effect of Ruksha Virechana,Lashuna Erandadi Kashaya and Patolamooladi Kashaya in Diagnosed Patients of Non-Alcoholic Steatohepatitis

The change in living habits due to increasing popularity of fast foods, sedentary lifestyle have given rise to lifestyle disorders and Non Alcoholic Steatohepatitis is one among them. Non Alcoholic Steatohepatitis (NASH) is a spectrum of Non Alcoholic Fatty Liver Disease (NAFLD) characterized by the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis.There is no direct reference to NASH in Ayurvedic literature but based on the etiopathogenesis, signs and symptoms it can be correlated to Yakritodara.NASH has no FDA approved therapeutics, so, it is need of the hour to search an effective hepatoprotective remedy from Ayurvedic treasure of therapeutics. Hence, the present study was designed as cross over single blind clinical study with the objectives of evaluating the combined efficacy of Amapachana,Ruksha virechana and Shamanoushadhi with Lashuna Erandadi Kashaya and Patolamooladi Kashaya in the management of NASH. Overall study showed marked improvement in 60% of cases and Moderate improvement in 26.66%. Hence,it can be concluded that the combined effect of therapy with Amapachana,Ruksha virechana and Shamanoushadhis (Lashuna Erandadi Kashaya and Patolamooladi Kashaya) has shown a significant role in relieving the signs and symptoms of subjects diagnosed with Non Alcoholic Steatohepatitis

Fatty liver is associated with advanced fibrosis but does not predict adverse outcomes in patients with chronic hepatitis B.

Hepatic steatosis is increasingly common and has been implicated in progression of liver fibrosis in chronic hepatitis B (CHB) patients. We aimed to investigate the impact of hepatic steatosis on liver fibrosis and clinical outcomes in CHB patients. Consecutive CHB patients who underwent transient elastography between 2013 and 2017 at a tertiary hospital were included in this longitudinal cohort study. Presence of hepatic steatosis was defined as controlled attenuation parameter, CAP≥248dB/m, while advanced liver fibrosis was defined as liver stiffness measurement, LSM≥9.4kPa. Cardiovascular events, liver-related complications, malignancy and mortality and a composite of these outcomes were evaluated with Kaplan-Meier analysis and Cox proportional hazards regression. Our study cohort included 614 patients with median follow-up of 45 (32-63) months. Hepatic steatosis was present in 294 patients (47.9%), and advanced liver fibrosis was present in 127 patients (21.0%). Presence of hepatic steatosis (OR: 1.956, 95% CI: 1.250-3.060) and diabetes mellitus (OR: 3.507, 95% CI: 2.069-5.944) was independently associated with advanced fibrosis. Advanced fibrosis was independently associated with composite outcome (HR: 2.496, 95% CI: 1.352-4.606), liver-related complications (HR: 3.765, 95% CI: 1.380-10.271) and mortality (HR: 3.632, 95% CI: 1.342-9.826), but not cardiovascular events and malignancy. Hepatic steatosis was not associated with any adverse outcomes. We conclude that hepatic steatosis is common and associated with advanced fibrosis in CHB patients. Unlike advanced fibrosis, hepatic steatosis does not predict adverse outcomes in CHB patients.

Lipidomics in Nonalcoholic Fatty Liver Disease: Exploring Serum Lipids as Biomarkers for Pediatric Nonalcoholic Fatty Liver Disease.

Disturbances in lipid metabolism play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Using lipidomics, an analytical technique that is used to broadly survey lipid metabolism, we searched for biomarkers in plasma that are correlated with the presence of hepatic steatosis in children with obesity. Lipidomics was performed in plasma samples of 21 children with obesity in whom steatosis was detected using proton magnetic resonance spectroscopy (H-MRS) and were compared with the lipidome of 21 samples of nonsteatotic subjects with obesity. Forty-two samples were analyzed (57% boys; median age 15 years). A total of 18 lipid classes constituting 839 different lipid species were identified. A statistically significant increase in alkyldiacylglycerol (TG[O]) and phosphatidylethanolamine (PE) species and a significant decrease in alkyl/alkenyl-phosphatidylethanolamine (PE[O]), alkyl/alkenyl-lysophosphatidylethanolamine (LPE[O]) and alkyl/alkenyl-phosphatidylcholine (PC[O]) was observed in children with hepatic steatosis compared with controls. Twelve individual lipid species of 3 lipid classes were significantly increased in steatotic subjects compared with controls. In this pilot study, we found statistically significant alterations in 5 major lipid classes and 12 individual lipid species in children with steatosis. These might be potential biomarkers for pediatric NAFLD. Lipidomic studies in larger cohorts of children are needed to determine the diagnostic value of these lipids and determine whether results can be generalized for different age groups and ethnic backgrounds.

Non-alcoholic steatohepatitis and progression of carotid atherosclerosis in patients with type 2 diabetes: a Korean cohort study

BackgroundThere is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.MethodsFrom a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1–2 years. Ultrasonographic findings at baseline and after 6–8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression.ResultsOf 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6–8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025–1.832; p < 0.05). Among patients with hepatic steatosis, only individuals with fibrosis showed significant association with atherosclerosis progression (AOR: 1.615, 95% CI 1.005–2.598; p < 0.05). The association between hepatic fibrosis and atherosclerosis progression was significant in all metabolic subgroups regardless of age, body mass index, presence of metabolic syndrome, or insulin sensitivity (all p < 0.05). Furthermore, subjects with hepatic steatosis & fibrosis and ≥ 4 components of metabolic syndrome criteria showed markedly increased risk of atherosclerosis progression (AOR: 2.430, 95% CI 1.087–5.458; p < 0.05).ConclusionsHepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.

Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B

Concomitant non-alcoholic fatty liver disease is common in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to study the effect of hepatic steatosis on the risk of fibrosis progression and the likelihood of HBsAg seroclearance. Treatment-naïve patients with CHB, normal alanine aminotransferase and low viraemia (serum HBV DNA <2,000 IU/ml) were prospectively recruited for baseline and 3-year transient elastography assessment. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1 stage increment of fibrosis. Hepatic steatosis and severe hepatic steatosis were defined as controlled attenuation parameter (CAP) ≥248 dB/m and ≥280 dB/m, respectively. A total of 330 patients (median age 50.5 years, 41.2% male, median HBV DNA 189 IU/ml) were recruited. Twenty-two patients (6.7%) achieved HBsAg seroclearance during follow-up, and the presence of hepatic steatosis was associated with a significantly higher chance of HBsAg seroclearance (hazard ratio 3.246; 95% CI 1.278-8.243; p= 0.013). At baseline, 48.8% and 28.8% of patients had steatosis and severe steatosis, respectively, while 4.2% had F3/F4 fibrosis at baseline, increasing to 8.7% at 3 years. The rate of liver fibrosis progression in patients with persistent severe steatosis was higher than in those without steatosis (41.3% vs. 23%; p= 0.05). Persistent severe hepatic steatosis was independently associated with fibrosis progression (odds ratio 2.379; 95% CI 1.231-4.597; p= 0.01). CAP measurements have predictive value in patients with virologically quiescent CHB. The presence of hepatic steatosis was associated with a higher risk of fibrosis progression but, paradoxically, a 3-fold increase in HBsAg seroclearance rate. Co-existing fatty liver disease in patients with chronic viral hepatitis B infection leads to worsening liver fibrosis, but also increases the chance of cure from hepatitis B virus. Routine bedside assessment of liver fat content is important for risk assessment in treatment-naïve patients with chronic hepatitis B.

MON-597 Non-Alcoholic Fatty Liver Disease Determined by MRI and Its Association with Metabolic Variables in Non-Diabetic Subjects

Non-alcoholic fatty liver disease determined by MRI and its association with metabolic variables in non-diabetic subjectsBackground: Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis (liver fat accumulation higher than 5% of liver weight) in the absence of other causes. Liver biopsy is recognized as a gold standard for diagnosis, but it is limited by the risks of serious complications. Besides that, the increasing prevalence of NASH led to improved imaging methods, such as Magnetic Resonance Imaging (MRI), that enable quantitative assessment of steatosis by quantifying the hepatic fat fraction (HFF), even with steatosis levels as low as 5.56%.Objective: The aim of this study was to evaluate the metabolic profile of patients without T2DM according to hepatic steatosis measured by MRI.Methods: This was cross-sectional study conducted in an Endocrinology Unity in Minas Gerais, Brazil. The study complied with the WMA Declaration of Helsinki and was approved by the Ethical Committee on Human Subject Research from the Faculty Patos de Minas. We recruited non-diabetic subjects aged above 20 years with hepatic steatosis detected by liver sonography. Exclusion criteria were alcohol consumption of more than 20 grams/day for female and 30 grams/day for male, ferritin serum levels above 1000 mg/dL, positive serology for hepatitis B or C and intake of medications known to produce hepatic steatosis. Included subjects underwent HFF quantification by MRI, and the degree of liver fatty infiltration was estimated by using chemical shift imaging. The following biochemical variables were assessed: fasting glucose and HbA1c, HOMA-IR, lipids, AST, ALT and GGT. Analysis: we grouped individuals according to the quartile of HFF and compared clinical and biochemical variables between the groups.Results: A total of 30 subjects (18 male and 12 females) were included. All subjects were overweight (10% overweight and 90% obese); 7 (23.3%) had 3 criteria and 16 (53.3%) had two criteria for MS. The only variable assessed herein that was different between males and females was HDL-c (40.5 vs 50.5 mg/dL, respectively, p=0.0255). ALT serum levels were significantly higher in subjects in the fourth quartile of HFF, when compared to those in the third quartile (76 vs 47 UI/L, respectively, p=0.037). The other clinical of biochemical variables assessed did not differ between the quartiles of HFF.Conclusion: our preliminary findings indicate that the biochemical variables related to metabolic homeostasis are poor predictors of the degree of liver fat in overweight non-diabetic subjects. Although screening for NAFLD is still a matter of debate, our results suggest that future discussions about this should take into account that excess body weight per se, independently from biochemical abnormalities, should be considered in the recommendations for screening non-diabetic subjects.

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0 × 10−4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

The association of serum total bile acid with non-alcoholic fatty liver disease in Chinese adults: a cross sectional study

BackgroundNon-alcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. Bile acids (BAs) have emerged as relevant signaling molecules that are associated with NAFLD development. This study was aimed to examine the association of serum total bile acids (TBAs) with NAFLD in a large population of Chinese subjects.MethodsThis cross sectional study recruited 152,336 participants from the Second Xiangya Hospital, China. NAFLD was diagnosed based on the presence of hepatic steatosis on ultrasonography, without significant alcohol consumption and other known causes for chronic liver disease. A multivariate logistic regression model was used to test for the association of serum TBAs with NAFLD, adjusting for conventional risk factors of NAFLD.ResultsA total of 27.4% of the participants had NAFLD. Patients with NAFLD had slightly higher TBA levels than those without, 3.4 vs. 3.0 μmol/L (p < 0.001). However, TBA levels were not associated with NAFLD in the multivariate logistic regression model, which adjusted for age, gender and other acknowledged risk factors for NAFLD (OR = 1.00. 95% CI: 1.00–1.00, p = 0.797).ConclusionsWe found that the serum TBA levels were not associated with NAFLD. Future studies in a large population, focusing on serum BA composition may improve the understating of the role of BAs in NAFLD.

Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis

BackgroundIn parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial. ObjectiveThe objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals. MethodsTotal PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans. ResultsIn a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05–2.08, P = 0.02). ConclusionOur data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

Oleuropein overrides liver damage in steatotic mice

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common disease in which oxidative stress plays a main role in causing organ damage. Oleuropein (Ole) is a phenolic compound with both significant anti-inflammatory and antioxidant properties. The aim of the present work has been focused on investigating the mechanisms by which Ole is able to improve liver damage, in the presence of hepatic steatosis. We evaluated the effects of Ole in female and male mice fed normal diet (ND) or high fat diet (HFD) for 8 weeks, adding or not Ole for the following 8 weeks. Ole induced a decrease in body, liver and heart weights and had an anti-inflammatory and antioxidant effects in HFD mice. Interestingly, in presence of the unhealthy diet, antioxidant effects of Ole overcome sex-related differences, improving liver damage.