“Hybrid exercise training improves liver steatosis and inflammation in a randomized trial of sedentary, obese women with non-alcoholic fatty liver disease”

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

BackgroundPediatric nonalcoholic fatty liver disease (NAFLD) has been recognized as a global health problem in pediatric. Owing to the limitations of the liver biopsy and the importance of screening and follow-up of NAFLD patients for hepatic steatosis and fibrosis, the noninvasive diagnostic methods are obviously needed. Abdominal ultrasonography has several limitations to assess the degree of fatty liver. Recently; transient elastography (TE, FibroScan) with controlled attenuation parameter (CAP) has been emerging as a relevant tool for assessing hepatic fibrosis and steatosis.The aim of this study was the noninvasive evaluation of hepatic fibrosis and steatosis by FibroScan with CAP through measuring liver stiffness and CAP values, respectively, in Egyptian children and adolescents with NAFLD proven by ultrasound.Patients and methods60 children and adolescents proven as NAFLD patients with ultrasound, were subjected to clinical examination and anthropometric measurements, liver enzymes (serum ALT, AST, ALP), lipid profile, fasting blood glucose (FBG) level and fasting serum insulin. Insulin resistance was calculated by homeostasis model assessment method of insulin resistance HOMA-IR. Hepatic fibrosis and steatosis were assessed by measuring liver stiffness and CAP, respectively, using FibroScan.ResultsThere were significant increasing of the laboratory data among NAFLD patients with increasing the ultrasonographic grades of liver steatosis (P=0.0001, liver steatosis score (CAP stage) by fibroscan (P=0.0001) and liver fibrosis degree by fibroscan among patients (P=0.0001). CAP values by FibroScan are significantly increasing parallel to the grades of ultrasonic steatosis in NAFLD patients with different grades of ultrasonic steatosis. Also, the values of liver stiffness by FibroScan are significantly increasing parallel to the grades of ultrasonic steatosis in NAFLD patients with different grades of ultrasonic steatosis. There were positive correlations between ultrasonic steatosis grades and each of CAP value, liver stiffness value among the studied NAFLD children.ConclusionThe data confirmed that Transient Elastography (TE) with CAP is a useful tool for detection of hepatic steatosis and fibrosis. There were positive correlations between ultrasonic steatosis grades and each of CAP value, liver stiffness value among the NAFLD children.

Nonalcoholic Fatty Liver Disease in Children: Where Are We?

We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5-5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 x 10(-5), adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% +/- 3.9) in comparison with the CG genotype (26.3% +/- 3.5) and GG genotype (33.3% +/- 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (beta 0.23 +/- 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.

Obstructive sleep apnoea and nonalcoholic fatty liver disease: risk factor or just coincidence?

Context:The perception of non-alcoholic fatty liver disease (NAFLD) as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM) patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis.Aims:To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT), new onset treatment naive T2DM and normal glucose tolerance (NGT) with and without NAFLD.Settings and Design:Cross-sectional clinic-based study.Subjects and Methods:152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients.Statistical Analysis Used:Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables), Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively.Results:NAFLD was significantly associated with higher alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT <25 U/L and GGT <15 U/L had highest negative predictivity whereas ALT >40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample.Conclusions:Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary diagnostic work-ups and early detection of NAFLD to reduce the risk of cirrhosis, hepatocellular carcinoma and classical cardiovascular disease in T2DM and IGT patients.

Where are we in the search for noninvasive nonalcoholic steatohepatitis biomarkers?

Evaluation and management of non-alcoholic steatohepatitis

Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease.

Background:Non-alcoholic fatty liver disease (NAFLD) is becoming recognized as a component of the metabolic syndrome and insulin resistance. There has been recent interest in the association between epicardial fat and atherosclerotic disease with increased risk of cardiovascular mortality and morbidity. Aim of the work: In this study we investigated the relationship between the metabolic syndrome with liver involvement and epicardial fat. Patients and methods: 85 patients who had the criteria of metabolic syndrome are subjected to thorough clinical evaluation. Abdominal circumference, body mass indexand waist/hip ratio were recorded for all patients. Laboratory investigations including urine, complete blood picture, fasting and postprandial blood glucose, uric acid, blood urea and creatinine,C-reactive protein (CRP) , lipid profile, liver enzymes and bilirubin were done to all patients. Ultrasonography was used to grade fatty liver and measure the thickness of epicardial fat. Results: Patients with high ALT levels have significantly higher (p<0.01) AST, fasting blood glucose (FBG), uric acid, triglyceride (TG) level, more epicardial fat and waist circumference (p<0.05) compared to those with normal levels. Patients with high grade of fatty liver have significantly higher total cholesterol, TG, FBG, AST, ALT, uric acid levels, more epicardial fat and waist circumference (p<0.01) compared to those with mild and moderate. ALT, FBG and TG are significantly higher in patients with detectable epicardial fat than those without (p<0.01). There were significant direct correlations between epicardial fat thickness with FBG (r= 0.324; p<0.01), TG (r= 0.217; p<0.05), AST (r= 0.493; p<0.01), ALT (r= 0.561; p<0.01), and grade of fatty liver (r= 0.479; p<0.01). Also there were significant direct correlations between FBG with waist circumference (r= 0.422; p = 0.01), TG level (r = 0.370; p<0.01), HDL-C (r = 0.284; p<0.05) and grade of fatty liver (r = 0.533; p = 0.01). There were significant direct correlations between grade of fatty liver with waist circumference (r= 0.264; p<0.05), TG (r= 0.407; p<0.01), uric acid (r= 0.288; p<0.05), and AST levels (r= 0.642 p<0.01). CRP was found correlated only with liver enzymes (r = 0.481;p<0.05). Simple logistic regression analysis revealed that epicardial fat thickness (mm) showed a trend in patients with NAFLD and metabolic syndrome. Conclusion: Echocardiographic assessment of epicardial adipose tissue, abdominal ultrasound assessment of NAFLD and transaminase level might serve as a reliable marker of visceral adiposity and more severe degree of metabolic syndrome.

Yet more evidence that MAFLD is more than a name change

Objective To study the efficacy of rosiglitazone combined with metformin on patients with non -alcoholic fatty liver diseases (NAFLD).Methods One hundred and twenty patients with non -alcoholic fatty liver disease were randomly divided into three groups:control group,rosiglitazone treatment group,and rosiglitazone combined with metformin treatment group,6 months were one cycle in all three groups.The evaluating indexes including body mass index( BMI),blood lipid,liver enzyme activities,fasting blood glucose ( FPG),fasting blood insulin ( FBI),insulin resistance index ( IRI),clinical symptoms,physical signs,and results of B - ultrasonic examination in liver.Results The patients treated with rosiglitazone or combined with metformin,levels of TC,TG,ALT,AST and IRI were obviously improved than those before treatment( P ＜ 0.05 ).The patients treated with rosightazone combined with metformin,levels of BMI were obviously improved than those before treatment( P ＜0.05).The total effective rates in these groups were significantly higher than that in control group( P ＜0.01 ).Conclusions The treatment of pioglitazone is safe and effective to NAFLD,and the therapeutic effect of combination use is superior to that of pioglitazone or metformin use alone. Key words: Rosiglitazone; Metformin; Non - alcoholic fatty live disease

Nonalcoholic Fatty Liver Disease: Its Mechanisms and Complications

Introduction: Severe obesity is often present with non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting. The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery and evaluate the association between OSA and severity of NAFLD. Methods: 141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery were investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation, and NAFLD activity score. The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI). Results: OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis in 72 (51.06%) patients. There was a statistical difference in BMI, waist circumstance, neck circumstance, high-density lipoprotein cholesterol, fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (p = 0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD (p < 0.05). Patients with steatosis of grades 1–3 had significantly elevated aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, triglycerides, fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR. Conclusion: Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.

Abnormal aminotransferase activity in women with polycystic ovary syndrome