Impact Of Nonalcoholic Fatty Liver Disease Research Articles

Impact of nonalcoholic fatty liver disease on intestinal immune cells

Nonalcoholic fatty liver disease (NAFLD) interacts with the intestinal immune system due to enterohepatic circulation and immune cell recruitment and recirculation. Intestinal immune imbalance promotes liver inflammation and fibrosis in the process of NAFLD, and meanwhile, NAFLD can cause disorders in the number and function of immune cells in the liver and intestinal tract. This article mainly elaborates on the impact of NAFLD on intestinal immune cells and briefly summarizes the new treatment methods for NAFLD targeting at intestinal immune cells, in order to provide a new understanding of the pathogenesis and treatment of NAFLD.

Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease. Its role in the development of extrahepatic co-morbidities is under investigation. The impact of NAFLD on the development of chronic kidney disease (CKD) is incompletely understood. The aim of this study was to explore the potential contribution of NAFLD on CKD in Germany. The Disease Analyzer Database covering 7.49 million cases in Germany was explored for patients diagnosed with NAFLD between 2000 and 2015 and was matched 1:1 to a cohort without NAFLD. Matching criteria included age, sex, physician, index year and co-diagnoses associated with CKD. The primary outcomes of this study were incidences of CKD and end-stage renal disease. A total of 48,057 patients with NAFLD were matched to 48,057 patients without NAFLD. Within 10 years of the index date, 17.1% of patients with NAFLD and 11.6% of patients without NAFLD were diagnosed with CKD (p < 0.001). On Cox regression analysis, NAFLD was significantly associated with the incidence of CKD (hazard ratio (HR) = 1.58, p < 0.001). This association remained significant across different age groups and subgroups such as patients with diabetes mellitus or arterial hypertension. There was no association between NAFLD and emerging dialysis therapy (HR = 1.25, p = 0.245). In this large database analysis in Germany, NAFLD constitutes an independent risk factor for CKD. Patients living with NAFLD should be monitored for a change in kidney function, facilitating therapeutic measures for kidney disease at an early stage.

Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma.

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.

Non-Alcoholic Fatty Liver Disease and Vascular Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. However, notably, the primary cause of morbidity and mortality in patients with NAFLD is cardiovascular disease (CVD), with fibrosis stage being the strongest disease-specific predictor. It is globally projected that NAFLD will become increasingly prevalent, especially among children and younger adults. As such, even within the next few years, NAFLD will contribute considerably to the overall CVD burden. In this review, we discuss the role of NAFLD as an emerging risk factor for CVD. In particular, this article aims to provide an overview of pathological drivers of vascular damage in patients with NAFLD. Moreover, the impact of NAFLD on the development, severity and the progression of subclinical and clinical CVD will be discussed. Finally, the review illustrates current and potential future perspectives to screen for CVD in this high-risk population.

Abstract P5-12-14: The impact of pre-existed and SERM-induced non-alcoholic fatty liver disease on breast cancer survival: A meta-analysis

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) was a common disease and a frequent side effect of endocrine therapy for breast cancer patients. This was the first meta-analysis to investigate the impact of NAFLD on breast cancer survival. Material and Methods: We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials database for relevant studies that investigated the correlation between NAFLD and breast cancer survival. Fixed- and random-effect meta-analyses were conducted according to the heterogeneity of enrolled studies. Subgroup analyses were based on whether NAFLD was induced by Selective-estrogen receptor modulator (SERM) administration. Results: Six cohorts from five studies including 935 NAFLD and 2102 non-NAFLD patients were enrolled. NAFLD was significantly associated with advanced age (p&amp;lt; 0.001), obesity (p&amp;lt; 0.001), lymph node metastasis (p = 0.003), hormone receptor positivity (p &amp;lt; 0.001) and human epidermal growth factor receptor 2 positivity (p = 0.008). NAFLD had no significant impact on disease free survival(DFS) [hazard ratio (HR) 0.95, 95% confidence interval (CI) = 0.48-1.87, p = 0.87] and overall survival (OS) (HR 1.28, 95% CI = 0.59-2.78, p = 0.53). In subgroup analyses, SERM-associated NAFLD showed no significant impact on DFS and OS. Nonetheless, non-SERM-associated NAFLD had a strong prognostic correlation with poor OS (HR 1.92, 95% CI = 1.09-2.06, p = 0.02). Conclusion: NAFLD had no significant impact on breast cancer survival. However, non-SERM-associated NAFLD implied increasing death risk. Future large-scale studies are warranted to further elucidate the correlation between NAFLD and breast cancer prognosis. Keywords: breast cancer; non-alcoholic fatty liver disease; selective estrogen receptor modulator; liver metastasis TABLES Table 1. Characteristics of studies enrolled in meta-analysisStudyCountryDesignNMedian follow-up (month)TNM StageNAFLD AssessmentLiver Metastasis AssessmentClinical EndpointsHormone ReceptorRelationship Between SERM-treatment and NAFLDDuran(2015)TurkeyRC107NAIVContrast-enhanced/ Non-Contrast CTNAOSNANon-SERM-associated NAFLDYan(2017)ChinaRC64664(7-91)I-IIIUSGUSGDFS, OSER+ and/or PR+SERM-associated NAFLDWu(2017)ChinaRC123030.7±24.9 32.4±26.3I-IIIUSGUSG/CT/MRILiver-MFSER/PR+799 ER/PR- 331NAZheng(2015)ChinaRC78576(14-122)I-IIIUSGNADFS, OSER/PR+SERM-associated NAFLDYang(2015) Cohort A*KoreaRC28NAII/IIIUSG/ Non-Contrast CT/ Contrast CTNADFS, OSNANon-SERM-associated NAFLDYang(2015) Cohort B*KoreaRC24NAII/IIIUSG/ Non-Contrast CT/ Contrast CTNADFS, OSNANon-SERM-associated NAFLDRC, retrospective cohort; NA, not available; CT, computed tomography; OS, overall survival; DFS, disease free survival; SERM, selective estrogen receptor modular; USG, ultrasonography; MRI, Magnetic resonance imaging; MFS, metastasis free survival.*Study by Yang et al. included two cohorts Table 2. Correlation Between NAFLD Presence and Clinicopathological FeaturesNAFLD(%)Non-NAFLD(%)P valueAge (years)&amp;lt;50354(24.7%)1081(75.3%)&amp;lt;0.001*&amp;gt;50397(32.4%)829(67.6)BMI (kg/m2)&amp;lt;25431(22.5%)1487(77.5%)&amp;lt;0.001*&amp;gt;25320(43.2%)421(56.8%)Tumor Size (mm)&amp;lt;20293(27.1%)790(72.9%)0.47220-50378(28.8%)935(71.2%)&amp;gt;5080(30.3%)184(69.7%)LN MetastasisYes540(40.9%)780(59.1%)0.003*No281(36.6%)486(63.4%)MenopausePre153(33.5%)304(66.5%)0.766Post96(32.4%)200(85.9%)ER/PR StatusER/PR +630(34.9%)1173(65.1%)&amp;lt;0.001*ER&amp;PR -121(14.1%)737(85.9%)Her-2Positive285(29.1%)696(70.9%)0.008*Negative245(23.8%)783(76.2%)RadiotherapyYes215(27.5%)566(72.5%)0.608No536(28.5%)1344(71.5%)*indicates statistical significance. Citation Format: Yu Song, Changjun Wang, Wei Huang, Yidong Zhou, Ziyuan Chen, Hanjiang Zhu, Feng Mao, Yan Lin, Xiaohui Zhang, Songjie Shen, Ying Zhong, Xin Huang, Chang Chen, Qiang Sun. The impact of pre-existed and SERM-induced non-alcoholic fatty liver disease on breast cancer survival: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-14.

The Impact of NAFLD and Waist Circumference Changes on Diabetes Development in Prediabetes Subjects

The aim of this study was to investigate the association of nonalcoholic fatty liver disease (NAFLD) with diabetes and the impact of waist circumference (WC) changes in subjects with prediabetes. We enrolled 6240 subjects with prediabetes who underwent health check-ups in 2007 and revisited our hospital at least once for a follow-up examination between 2008 and 2013. Subjects were stratified by WC changes into three groups. The relative risks (RRs) for diabetes according to the NAFLD status and WC change were evaluated. The prevalence of NAFLD was 45.4% (2830/6240). During follow-up, the incidence of diabetes was 8.1% (505/6240). Subjects with NAFLD had a higher incidence of diabetes and the adjusted RRs were 1.81 (95% confidence interval [CI], 1.47 to 2.21), after adjustment for potential confounding factors. The adjusted RRs were related to WC changes. The adjusted RRs for diabetes according to tertiles of WC change (first, second, and third tertile) were 1.64 (95% CI, 1.08 to 2.49), 1.73 (95% CI, 1.28 to 2.34), and 2.04 (95% CI, 1.42 to 2.93), respectively. NAFLD has significantly increased risk of incident diabetes in subjects with prediabetes. The risk for diabetes is gradually increased with tertiles of WC change.

1013 The Effect of Steatosis on the Clinical Course of Autoimmune Hepatitis

INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) is a common liver disease in western developed countries. NAFLD is increasingly encountered alongside other chronic liver diseases, such as autoimmune hepatitis (AIH). The impact of NAFLD on the clinical course of AIH is unclear and one recent single center study suggested a worse clinical outcome for patients with AIH and concurrent steatohepatitis. We aimed to determine the frequency of steatosis and steatohepatitis in patients with AIH and the effect on treatment outcomes. METHODS: The cohort consisted of 61 AIH patients from a single, large, tertiary referral center with pre-treatment liver biopsies and available clinical data. Biliary overlap syndromes were excluded. Two liver pathologists recorded histological findings, including quantification of steatosis and steatohepatitis. One clinical reviewer recorded 96 clinical/laboratory variables. Non-parametric (Spearman rho) tests were used and correlations with P &lt; 0.05 were deemed significant. Non parametric t-tests were used to compare various degrees of steatosis (none, mild/moderate) with clinical variables and P &lt; 0.05 were deemed significant. RESULTS: Patients were followed for mean of 3.1 ± 3 years after diagnosis. Mean age at diagnosis was 49.9 ± 19.1 years and mean BMI at diagnosis was 28.3 ± 7. In this cohort, 31.7% of patients had steatosis on histology, and out of those 75.0% had mild and 25.0% had moderate degree of steatosis. Strikingly, there were no cases of steatohepatitis. The degree of steatosis was positively correlated with increasing age and BMI, (r = 0.44, CI 0.17-0.65, P ≤ 0.001and r = 0.49, CI 0.15-0.73, P = 0.01, respectively). However, there was no correlation between degree of steatosis and initial treatment failure, ALT at 12 months of treatment, chances of biochemical remission, development of cirrhosis, or the dose of steroid required for biochemical remission. Furthermore, there was no difference in these outcomes when those with versus without steatosis were compared. CONCLUSION: Data from this single center study suggest that AIH patients with mild and moderate steatosis have the same clinical course and response to treatment as those without steatosis.. The increasing prevalence of superimposed NAFLD in AIH warrants longitudinal observational multi-center studies focused on the frequency of steatohepatitis, and the impact of steatosis on the natural history of AIH.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

The Clinical and Economic Burden of Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) will be the dominant and most impactful liver disease for the next generation. As the obesity and diabetes epidemic continues and the general populations in most industrialized countries become older, NAFLD and its progressive subtype nonalcoholic steatohepatitis (NASH) will have a significant clinical and economic impact on society, both in the USA and globally. This manuscript provides a review of recently published articles that detail the impact of NAFLD and NASH. Overall, the literature shows that NAFLD is the most common liver disease globally, and that NASH is poised to become one of the dominant drivers of cirrhosis and hepatocellular carcinoma. Decompensated cirrhosis due to NASH will soon be the leading indication for liver transplantation. Costs increase significantly as patients progress to later stages of liver disease. Overall, the annual direct medical costs related to NAFLD are estimated to be near $100 billion in the USA and over €35 billion in Europe. The price tag almost triples if indirect costs are included. The global impact of NAFLD and NASH is projected to increase, with a 178% increase in liver-related deaths by 2030. The clinical and economic impact of NAFLD and NASH will be immense in the upcoming decades. This highlights the great need for better screening, surveillance, linkage to care, risk stratification, and treatment options.

Association Between Metabolic Abnormalities and Non-Alcoholic Fatty Liver in Obese Premenopausal Women

Non-alcoholic fatty liver disease (NAFLD) is frequently related to obesity and metabolic alterations. This study aimed to assess the relation between NAFLD and metabolic syndrome (MS) in obese premenopausal women and investigate the impact of NAFLD on occurrence of metabolic syndrome components. The study comprised 180 non-smoking premenopausal obese women. They were 90 with NAFLD and 90 with normal liver, aged 25 to 35 years. Abdominal ultrasonography was used to diagnose fatty liver disease. MS was diagnosed according to the Adult Treatment Panel III criteria. Metabolic syndrome was found in 22.2% and in 83.3% of the normal and fatty liver cases, respectively, with significant difference. Cases with NAFLD had significantly higher levels of triglyceride, glucose, ALT, cholesterol, HOMA-IR and waist circumference than those than those with the normal fatty liver. In fatty liver group, the majority of cases had central obesity (88.8%), followed by hypertriglyceridemia (85.5%), hyperinsulinemia (84.4 %), hyperglycemia (83.3%) and hypertension (81.1%). All metabolic syndrome components were significantly elevated in the cases with fatty liver than those with in normal liver cases. The strongest associations of an individual component of meta­bolic syndrome with NAFLD were hypertriglyceridemia and low HDL-cholesterol. A higher percentage of NAFLD was observed in cases with three components followed by four components of the metabolic syndrome. NAFLD is correlated positively with metabolic risk components. It was associated with higher ratios of metabolic components; hypertriglyceridemia and low HDL-cholesterol level had the strongest positive association. This suggests the importance of these components in screening of NAFLD among obese premenopausal women.

NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH ONSET OF ATRIAL FIBRILLATION AT A YOUNGER AGE: A NATIONWIDE STUDY

The incidence of non-alcoholic fatty liver disease (NAFLD) has been rising partly in consequence to the rising obesity epidemic. Previous studies support the link between NAFLD and the onset of atrial fibrillation (AF). We aim to assess the impact of NAFLD on patients with AF, as data is limited on

Non-alcoholic fatty liver disease as a risk factor for female sexual dysfunction in premenopausal women.

ObjectiveNon-alcoholic fatty liver disease (NAFLD) has become a common and important chronic liver disease worldwide. Previous studies have indicated that NAFLD has an adverse effect on the quality of life, but information is lacking about the impact of NAFLD on female sexual dysfunction. The aim of this study was to determine the association between NAFLD and female sexual dysfunction in premenopausal women.MethodsThis retrospective study consisted of premenopausal women who were sexually active and visited the outpatient clinic for a routine health check-up between January 2010 and December 2011. Based on the examination of the liver ultrasound scan, the study population was divided into 2 groups: cases with NAFLD and normal controls (cases without NAFLD). The female sexual function was compared between the two groups of cases. For the assessment of sexual function, a female sexual function index (FSFI) questionnaire was used.ResultsFour hundred seventy women were included, and the prevalence of NAFLD and female sexual dysfunction were 67/470 (14.3%) and 238/470 (50.6%), respectively. Cases with NAFLD had a lower total FSFI score and higher rate of female sexual dysfunction than the normal control [median score of total FSFI (interquartile range): 24.7 (21.9–27.8) in NAFLD vs. 26.7 (23.7–29.8) in normal control, p<0.005; the female sexual dysfunction: 64.2% in NAFLD vs. 48.4% in normal control, p<0.05]. This difference in female sexual dysfunction between the two groups remained significant after adjustment.ConclusionNAFLD is associated with female sexual dysfunction in premenopausal women.

Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study.

Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown. This study investigated the longitudinal association between NAFLD and CAC score. This study is a longitudinal cohort study performed in a healthcare center. Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography. CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed. More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043). NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

Nonalcoholic Steatohepatitis Score is an Independent Predictor of Right Ventricular Dysfunction in Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease and impaired left ventricular (LV) function, yet the impact of NAFLD on right ventricular (RV) function remains unclear. We investigate the RV functional properties in patients with NAFLD. Ninety consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and sex-matched controls were included. All patients underwent an echocardiographic examination. RV function was evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE). Mean fibrosis stage and nonalcoholic steatohepatitis (NASH) scores were 1.3±1.1 and 5.2±1.6, respectively. NAFLD patients displayed decreased RV function compared to controls. NAFLD patients with liver fibrosis (67 patients) had significantly lower RV function assessed by GLS (global longitudinal strain) compared to patients without liver fibrosis (18.9±3.4% vs. 21.6±2.3%, P<0.001). NASH score ≥5 was associated with lower RV-GLS (18.9±3.1% vs. 21.0±3.4%, P=0.006). NASH score inversely correlated with RV-GLS (r=-0.370, P<0.001) such as patients with impaired RV-GLS (<19%) showed significantly higher NASH score compared to normal RV-GLS group (5.8±1.4 vs. 4.8±1.7, P=0.009). Logistic regression analysis revealed that NASH score was an independent predictor of impaired RV function in patients with NAFLD. Patients with NAFLD have impaired RV function. NASH score inversely correlates with RV-GLS and independently predicts impaired RV function in patients with NAFLD.

Economic and Quality-of-Life Implications of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a very common chronic liver disease worldwide, is on the rise following the trend of increasing prevalence of obesity, is the second most common indication for liver transplantation, and is an important cause for hepatocellular carcinoma. Despite the increasing recognition of NAFLD as an important chronic liver disease, little has been published on the economic and health-related quality of life (HR-QOL) impact of NAFLD. We reviewed the current literature related to the economics and HR-QOL of NAFLD and found that increased costs and decreased HR-QOL were associated with NAFLD.

P0983 : Association between macro-nutrient intake and presence of nonalcoholic fatty liver disease in the Rotterdam study: a population-based study

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification and increased prevalence of cardiovascular disease in many cross-sectional studies. However, whether NAFLD per se affect the progression of coronary artery calcification still remains to be elucidated. The aim of this study was to investigate the prospective association between NAFLD and the incidence and progression of coronary artery calcification (CAC) in a longitudinal cohort study. Methods: Among 1732 subjects who underwent serial CAC score evaluation, we evaluated 847 subjects with NAFLD and 885 subjects without NAFLD. Only those without viral hepatitis, significant alcohol consumption and known coronary artery disease were enrolled. NAFLD was diagnosed by ultrasonography in subjects without significant alcohol consumption. CAC score was evaluated by the Agatston method with multi-detector computed tomography. Results: The baseline CAC score was higher in those with NAFLD, and greater number of these subjects showed progression (48.8% vs. 38.4%, p < 0.001 in subjects with vs. without NAFLD). NAFLD was prospectively associated with progression of CAC score (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.26–1.85, p < 0.001). Noticeably, the impact of NAFLD significantly varied with the severity of baseline coronary atherosclerosis. In those without calcification at baseline, NAFLD significantly affected progression of atherosclerosis (adjusted OR 1.54, 95%CI 1.05–2.27, p =0.028), after adjustment for age, hypertension diabetes mellitus, dyslipidemia, smoking, gender and body mass index. Analysis according to the severity of NAFLD showed that NAFLD in its more severe form promotes progression of CAC (adjusted OR 1.77, 95%CI 1.08–2.88, p =0.022). However, in subjects with baseline CAC, NAFLD did not affect progression of CAC (p =0.482). Conclusions: NAFLD plays a role in early stage of coronary atherosclerosis, and it also seems that greater degree of NAFLD affects the progression independent of traditional risk factors. Thus NAFLD does not solely show a simple association, but also plays a role in the development and progression of coronary artery disease.

Abstract P081: Increased Hepatic Fat Is Associated With A More Atherogenic Lipoprotein Profile In Adolescents

Introduction: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common liver disease in pediatrics, and it has been estimated to affect more than one third of obese adolescents in the United States. In adolescents with NAFLD, traditional markers of increased cardiovascular risk are commonly reported including elevated triglycerides and reduced HDL-cholesterol levels. Despite the fact that lipoproteins are critically involved in atherogenesis and cardiovascular disease, the independent impact of NAFLD on size and particle concentration of major lipoproteins remains less well described and studies in pediatric population are particularly scarce. Hypothesis: In the current study, we assessed the hypothesis that in adolescents, high hepatic fat would have a strong association with an atherogenic pattern of lipoprotein particle size and concentration. Methods: Hispanic-American overweight and obese adolescents (n=50) were recruited from pediatric clinics at Emory Children’s Center and from nearby community centers through flyers and presentations at community events. We evaluated their hepatic fat content by magnetic resonance spectroscopy and measured lipoprotein particles by nuclear magnetic resonance (Liposcience, Raleigh, NC). Results: Using the 5% hepatic fat to stratify subjects with low (n=13) and high hepatic fat (n=37), adolescents with high hepatic fat have undesirable lipoprotein subclass profiles, including larger VLDL particle size (51.2 ± 1.36 vs. 44.8 ± 1.31 nm, p=0.010), more large VLDL particle numbers (5.75 ± 0.93 vs. 1.32 ± 0.18 nmol/L, p&lt;0.001), and fewer large HDL particles (4.15 ± 0.33 vs. 5.69 ± 0.67 μmol/L, p=0.033). Strong correlations were found between hepatic fat and the number of large VLDL particles (r=0.521, p&lt;0.001), VLDL particle size (r=0.439, p=0.002), and small, dense LDL particle numbers (r=0.291, p=0.040). Conclusions: The amount of hepatic fat is closely related to the presence of large VLDL particle and small dense LDL, two important predictors of CVD. This suggests that hepatic fat and the associated dyslipidemia have interrelated mechanisms. Further studies with histologic assessment of NAFLD (liver biopsies) will be needed to confirm our findings and to explore causation.

Nonalcoholic Fatty Liver Disease: Its Mechanisms and Complications

Nonalcoholic Fatty Liver Disease: Its Mechanisms and Complications

How common is non‐alcoholic fatty liver disease in the Asia–Pacific region and are there local differences?

Risk factors for development of non-alcoholic steatohepatitis include obesity, especially central adiposity, glucose intolerance or type 2 diabetes mellitus (T2DM), and dyslipidemia. Non-alcoholic fatty liver disease (NAFLD) is now considered a manifestation of metabolic syndrome. During the last two decades, NAFLD has become the most common chronic liver disease in North America and Europe, but until recently was thought to be uncommon (perhaps due to the lack of study) in Asia. Fatty liver can be identified on imaging modalities (ultrasonography, computed tomography scans, and magnetic resonance imaging) with high sensitivity, but steatohepatitis and fibrosis cannot be distinguished. Thus, an inherent drawback in studying the epidemiology of NAFLD is the lack of definitive laboratory tests, no uniform definition-with different studies using cut-off values of alcohol consumption from <20 g/week to 210 g/week, and case selections where biopsy was used for definition. In studies outside the region, the prevalence of NAFLD varies from 16% to 42% by imaging, and 15-39% of liver biopsies. The major risk factors for NAFLD, central obesity, T2DM, dyslipidemia, and metabolic syndrome, are now widely prevalent and are increasing geometrically in the Asia-Pacific region. It is therefore not surprising that NAFLD is common in this region. Estimates of current prevalence range from 5% to 30%, depending on the population studied. Central obesity, diabetes, and metabolic syndrome are the major risk factors. To date, however, data on the natural history and impact of NAFLD causing serious significant chronic liver disease are lacking and there is a need for prospective, cooperative studies.

Effects of nonalcoholic fatty liver disease on the development of metabolic disorders

Nonalcoholic fatty liver disease (NAFLD) is considered to be the liver component of metabolic syndrome. However, the impact of NAFLD on metabolic syndrome is unclear. The aim of this study was to explore the influence of NAFLD on the development of metabolic disorders. Patients with NAFLD and an age, sex, and occupation-matched control group were recruited from employees of Bao-Steel Group (Shanghai, China) who had received medical check-ups biennially between 1995 and 2002. Anthropometric and laboratory data, and incidence of metabolic disorders were assessed at baseline and at follow-up of at least 4 years. SPSS 11.5 was used for statistical analysis. The study consisted of 358 patients (326 men and 32 women) and 788 matched controls (711 men and 77 women) with a similar mean age of 39.0 years and median follow-up of 6 years. At the end of follow-up, incidence of obesity (47.6% vs 19.5%), hypertension (69.6% vs 16.3%), hypertriglyceridemia (39.1% vs 16.3%), hypercholesterolemia (24.5% vs 17.3%), impaired fasting glucose (IFG) (25.1% vs 11.6%), diabetes mellitus (20.3% vs 5.2%) and multiple metabolic disorders (MMD) (56.3% vs 16.3%) were significantly higher in the fatty liver group than the control group. Interestingly, the mean alanine aminotransferase (ALT) level in patients with fatty liver significantly decreased at follow-up compared with baseline (28.56 +/- 18.86 vs 31.51 +/- 18.34 U/L, P < 0.05). To separate the effects of obesity from fatty liver, the subjects were re-classified according to the presence of obesity and fatty liver at baseline. The incidence of hypertension (61.1% vs 41.3%), hypertriglyceridemia (38.1% vs 15.0%), hypercholesterolemia (29.9% vs 16.6%), IFG (21.3% vs 10.0%) and diabetes (11.1% vs 4.3%) were significantly higher in the fatty liver group without obesity (n = 84) than in the group with without fatty liver or obesity (n = 614). In addition, the incidence of hypertension (72.9% vs 57.4%), hypertriglyceridemia (39.4% vs 22.7%) and diabetes (23.2% vs 8.4%) was higher in the group with fatty liver and obesity (n = 274) than in the group with obesity alone (n = 174). The presence of NAFLD might predict the development of metabolic disorders due to insulin resistance, rather than obesity itself. ALT levels decreased over time in patients with fatty liver.