Non-alcoholic Fatty Liver Disease Liver Fat Score Research Articles

Prospective Association between Gestational Diabetes and Subsequent Abnormal Liver Function Scores 9 to 16 Years after Pregnancy

Chronic hyperglycemia is a risk factor for liver dysfunction. Women with gestational diabetes mellitus (GDM), glucose intolerance first recognized in pregnancy, may identify a population of individuals at an increased risk for liver complications. However, large prospective studies examining liver function following a GDM pregnancy are lacking. The Diabetes & Women’s Health (DWH) Study (2012-2014) followed women with and without GDM in the Danish National Birth Cohort (DNBC). DNBC was a population-based cohort study of pregnant Danish women (1996-2002). At 9-16 years postpartum, the DWH Study conducted a clinical exam and collected bio-specimens on 607 of 1,274 women with GDM and 619 of a random sample of 1,457 women without GDM during the index DNBC pregnancy. Markers of liver function measured at follow-up included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Liver function scoring indices were used to assess liver capacity including: nonalcoholic fatty liver disease liver fat score (NAFLD-LFS), fatty liver index (FLI), hepatic steatosis index (HSI), and liver fat percentage. The mean (standard deviation) age (years) at follow-up for women without and with prior GDM was 43.4 (4.5) and 43.8 (4.6), respectively. Women with prior GDM had an increased risk at follow-up of elevated NAFLD-LFS (Adjusted Relative risk [RR], 2.34; 95% CI, 1.68-3.27), FLI (RR, 1.59; 95% CI, 1.27-1.99), and HSI (RR, 1.44; 95% CI, 1.21-1.71) adjusted for pre-pregnancy BMI and other relevant risk factors compared to women without prior GDM. Women with prior GDM also had a significantly higher fatty liver percentage (Adjusted difference (%), 1.93; 95% CI, 1.10-2.77). Women with GDM during pregnancy were at an increased risk for subsequent abnormal liver function 9-16 years postpartum. GDM may serve as another risk indicator for the early identification and prevention of liver dysfunction. Disclosure S. Donnelly: None. S. Hinkle: None. S. Rawal: None. L. Grunnet: None. J.E. Chavarro: None. A.A. Vaag: Employee; Self; AstraZeneca. J. Wu: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. M. Li: None. A.A. Bjerregaard: None. A. Thuesen: None. R.E. Gore-Langton: None. E.C. Francis: None. F. Hu: None. M.Y. Tsai: None. S.F. Olsen: None. C. Zhang: None.

Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction.

The prevalence of non-alcoholic-fatty-liver-disease (NAFLD) is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of MS after six months of follow-up and to assess the role of fiber content in metabolic outcomes. Seventy obese individuals from the RESMENA (Reduction of Metabolic Syndrome in Navarra) study were evaluated at baseline and after six months of energy-restricted nutritional intervention (American Heart Association (AHA) and RESMENA dietary groups). Dietary records, anthropometrical data, body composition by dual energy X-ray absorptiometry (DXA), and routine laboratory measurements were analyzed by standardized methods. Regarding liver status, cytokeratin-18 fragments and several non-invasive scores of fatty liver were also assessed. The RESMENA strategy was a good and complementary alternative to AHA for the treatment of obesity-related comorbidities. Participants with higher insoluble fiber consumption (≥7.5 g/day) showed improvements in fatty liver index (FLI), hepatic steatosis index (HIS), and NAFLD liver fat score (NAFLD_LFS), while gamma-glutamyl transferase (GGT) and transaminases evidenced significant improvements as a result of fruit fiber consumption (≥8.8 g/day). Remarkably, a regression model evidenced a relationship between liver status and fiber from fruits. These results support the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.

Nonalcoholic fatty liver disease liver fat score (NAFLD-LFS) could be used for the assessment of NAFLD in women with PCOS

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome.

What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)? Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS. Obesity and IR are frequently present in both women with PCOS and subjects having NAFLD. The coexistence of PCOS and NAFLD might synergistically increase the risk for both type 2 diabetes (T2DM) and cardiovascular disease (CVD). LAP, calculated from waist circumference (WC) and triglycerides (TGs) concentrations [(WC-58) × TGs], has been shown to represent an integrated marker of cardiometabolic risk in women with PCOS. This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013. The study was done at the university hospitals in Belgrade, Serbia and Thessaloniki, Greece. All subjects underwent anthropometric measurements and analyses of fasting blood glucose, insulin, lipids, total testosterone and SHBG, as well as liver tests (transaminases, γ-glutamyltransaminase, total bilirubinand alkaline phosphatase). Calculations for a NAFLD liver fat score (NAFLD-LFS) (with, accordingly, determination of metabolic syndrome and testing for T2DM) as well as homeostasis model assessment of IR (HOMA-IR), LAP as a marker of visceral adiposity, and free androgen index (FAI) were performed. We evaluated the prevance of NAFLD and analyzed associations of the above variables with NAFLD. NAFLD was more prevalent in patients with PCOS than in controls (50.6 versus 34.0%, respectively). Women with PCOS had higher readings for WC, LAP, insulin and HOMA-IR, total cholesterol and TGs than controls (P < 0.001). In PCOS women, the NAFLD-LFS significantly (P < 0.001) correlated with WC, BMI, glucose, HOMA-IR, TGs, LAP and FAI. In multivariate logistic regression, HOMA-IR and LAP were independently associated with NAFLD (P ≤ 0.001). A possible weakness of the study may be the absence of structural confirmation of liver status. Hovewer, liver biopsy is invasive, difficult to perform in large populations and carries some risk of complications while magnetic resonance spectroscopy does not provide any information regarding the presence of fibrosis and is not routinely available. Another possible limitation could be the measurement of total testosterone by radioimmunoassay, which can be inaccurate when determining low levels of testosterone. Finally, fewer controls than subjects in the study group could have affected the significance of the results. There is a debate on the most accurate clinical method for diagnosing liver disease as an early predictor of T2DM and CVD in general population and in PCOS women. There current study provided data on this issue from a cohort of Caucasian women with PCOS. The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests.

Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008-2011).

Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB-4, and Forns index. Significant liver fibrosis was defined as FIB-4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass [kg]/body mass index (kg/m(2) ]) was calculated using dual-energy X-ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P < 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76-2.68 depending on the subgroup, all P < 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52-0.67, all P < 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB-4 and Forns index) produced similar results. Sarcopenia is associated with significant liver fibrosis in subjects with NAFLD, and the association is independent of obesity and insulin resistance.

Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease.

To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD). Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to (13)C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD. Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD. H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.

The Effect of Helicobacter pylori Eradication on Liver Function Test and Metabolic Profile in Dyspeptic Patients With Non-Alcoholic Steatohepatitis

Background: Nonalcoholic steatohepatitis (NASH) is part of a broad spectrum of nonalcoholic fatty liver diseases that can lead to cirrhosis. Limited clinical data suggest that Helicobacter pylori (HP) infection might be associated with NASH. Objectives: This randomized double blind clinical trial was designed to determine the short-term effects of HP eradication on liver function tests (LFT) and metabolic profile (biochemical parameters and anthropometric measurements) in a sample of dyspeptic NASH patients. Patients and Methods: Referred dyspeptic patients, with positive antibodies to HP, and the evidence of fatty liver in ultrasonography, were included. After excluding other causes, participants with persistent elevated serum aminotransferase levels were presumed to have NAFLD. Those with NAFLD liver fat score greater than (-0.64) and positive urea breath test (UBT) were enrolled. They were randomly assigned to lifestyle modification alone or lifestyle modification plus HP eradication groups. Quadruple therapy for HP eradication was performed during two weeks. HP eradication was documented by UBT. Liver fat content, fasting serum glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triglyceride, cholesterol, high and low-density lipoprotein, homeostatic model assessment of insulin resistance and anthropometric measurements (body mass index and waist circumference) were checked at baseline and 12 week post-treatment. Results: One hundred dyspeptic NASH patients (50 male) were enrolled. Their average age in HP treatment group was 36.6 ± 6.4 and 36.7 ± 6.17 years, in control group, respectively. Repeated measure analysis of variance showed a significant reduction in anthropometric measurements and laboratory parameters, in both groups, during the study; however, no significant difference was observed between the two groups, with regard to anthropometric measurements and laboratory parameters, at the end of study. Conclusions: The eradication of HP in dyspeptic NASH patients did not provide any additional improvement in laboratory parameters and anthropometric measurements, compared to lifestyle modification alone.

Associations of coffee consumption with markers of liver injury in the insulin resistance atherosclerosis study.

BackgroundCoffee consumption has been associated with reduced risk of developing type 2 diabetes mellitus (T2DM) however, the mechanism for this association has yet to be elucidated. Non-alcoholic fatty liver disease (NAFLD) characterizes and predicts T2DM yet the relationship of coffee with this disorder remains unclear. Our aim was to investigate the associations of coffee with markers of liver injury in 1005 multi-ethnic, non-diabetic adults in the Insulin Resistance Atherosclerosis Study.MethodsDietary intake was assessed using a validated 114-item food frequency questionnaire. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and fetuin-A were determined in fasting blood samples and the validated NAFLD liver fat score was calculated. Multivariate linear regression assessed the contribution of coffee to variation in markers of liver injury.ResultsCaffeinated coffee showed significant inverse associations with ALT (β = −0.08, p = 0.0111), AST (β = −0.05, p = 0.0155) and NAFLD liver fat score (β = −0.05, p = 0.0293) but not with fetuin-A (β = 0.04, p = 0.17). When the highest alcohol consumers were excluded, these associations remained (ALT β = −0.11, p = 0.0037; AST β = −0.05, p = 0.0330; NAFLD liver fat score β = −0.06, p = 0.0298). With additional adjustment for insulin sensitivity, the relationship with ALT remained significant (ALT β = −0.08, p = 0.0400; AST β = −0.03, p = 0.20; NAFLD liver fat score β = −0.03, p = 0.27). There were no significant associations of decaffeinated coffee with liver markers.ConclusionsThese analyses indicate a beneficial impact of caffeinated coffee on liver morphology and/or function, and suggest that this relationship may mediate the well-established inverse association of coffee with risk of T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0321-3) contains supplementary material, which is available to authorized users.

Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008–2011)

Although sarcopaenia is associated with obesity-related comorbidities, its influence on non-alcoholic fatty liver disease (NAFLD) or steatohepatitis has not been fully determined. We aimed to investigate the direct relationship between sarcopaenia and NAFLD or steatohepatitis in the general population. We conducted a cross-sectional study using nationally representative samples of 15,132 subjects from the Korea National Health and Nutrition Examination Surveys 2008-2011. Subjects were defined as having NAFLD when they had higher scores from previously validated NAFLD prediction models such as the hepatic steatosis index, comprehensive NAFLD score and NAFLD liver fat score. BARD and FIB-4 scores were used to define advanced fibrosis in subjects with NAFLD. The skeletal muscle index (SMI) [SMI(%)=total appendicular skeletal muscle mass (kg)/weight (kg)×100] measured by dual-energy X-ray absorptiometry was used to diagnose sarcopaenia with cut points of 32.2% for men and 25.5% for women. SMI was inversely correlated with all NAFLD predicting scores (Ps<0.001). After stratification, sarcopaenic subjects had an increased risk of NAFLD regardless of obesity (odds ratios [ORs]=1.55 to 3.02, depending on models; all Ps<0.001) or metabolic syndrome (ORs=1.63 to 4.00, all Ps<0.001). Multiple logistic regression analysis also demonstrated this independent association between sarcopaenia and NAFLD after adjusting for confounding factors related to obesity or insulin resistance (ORs=1.18 to 1.22, all Ps<0.001). Furthermore, among the NAFLD population, subjects with lower SMIs were likely to have advanced fibrosis compared with non-sarcopaenic individuals (BARD and FIB-4: ORs=1.83 and 1.69, respectively; both Ps<0.001). Compared with non-exercised subjects, individuals who exercised regularly had a lower risk of NAFLD (p<0.001), particularly among obese people with well-preserved muscle mass. Sarcopaenia is associated with increased risks of NAFLD and advanced fibrosis, independent of obesity or metabolic control.

Higher fructose intake is inversely associated with risk of nonalcoholic fatty liver disease in older Finnish adults

High fructose intake has been suggested to be a key factor that induces nonalcoholic fatty liver disease (NAFLD), but the evidence from large epidemiologic studies is lacking. We examined the cross-sectional association between fructose intake and NAFLD by using the Fatty Liver Index (FLI) and the NAFLD liver fat score. The Helsinki Birth Cohort Study investigated 2003 Finnish men and women born in 1943-1944 in Helsinki who participated in a clinical health examination in the years 2001-2004. Trained study nurses measured weight, height, and waist circumference, and body mass index was calculated. Laboratory staff drew fasting blood for measurements of triglycerides and γ-glutamyl-transferase. The FLI and the NAFLD liver fat score were calculated on the basis of these measurements. Habitual fructose and other dietary intake over the past year were assessed by using validated and standardized 131-item food-frequency questionnaires. Data were analyzed in a cross-sectional manner by using logistic regression modeling with statistical software. In a model adjusted for age, sex, and energy intake, participants in the highest fructose intake quartile (range: 29.2-88.0 g/d) had lower risk of NAFLD assessed by using the FLI (OR: 0.56; 95% CI: 0.42, 0.75; P-trend < 0.001) and NAFLD liver fat score (OR: 0.72; 95% CI: 0.53, 0.99; P-trend < 0.001) than that of the lowest intake quartile (range: 2.2-15.2 g/d). This association remained after adjustment for educational attainment, smoking, physical activity, and other dietary variables only for the FLI (OR: 0.68; 95% CI: 0.47, 0.84; P-trend < 0.05). Our cross-sectional results did not support the current hypothesis that high intake of fructose is associated with a higher prevalence of NAFLD as assessed by using the FLI and NAFLD liver fat score.

Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.

Several steatosis biomarkers are available with limited independent validation. To determine diagnostic value and limitations of several steatosis biomarkers using liver biopsy as reference standard in a large cohort of patients with suspected NAFLD. Three hundred and twenty-four consecutive liver biopsies were included. Histological steatosis was categorised as none (<5%), mild (5-33%), moderate (33-66%) and severe (>66%). Five steatosis biomarkers were measured: fatty liver index (FLI), NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI), visceral adiposity index (VAI) and triglyceride × glucose (TyG) index. Steatosis grades prevalence was: none 5%, mild 39%, moderate 30% and severe 27%. Except for VAI, the steatosis biomarkers showed a linear trend across the steatosis grades. However, their correlation with the histological amount of steatosis was only weak-moderate. All steatosis biomarkers had an adequate diagnostic accuracy for the presence of steatosis: AUROCs for FLI, LFS, HSI, VAI and TyG were 0.83, 0.80, 0.81, 0.92 and 0.90. However, their ability to quantify steatosis was poor: none of them distinguished between moderate and severe steatosis and the AUROCs for predicting steatosis >33% were 0.65, 0.72, 0.65, 0.59 and 0.59 for FLI, LFS, HSI, VAI and TyG. Both fibrosis and inflammation significantly confounded the association between steatosis biomarkers and steatosis. The steatosis biomarkers were all correlated with HOMA-IR, independent from histological steatosis. All five steatosis biomarkers can diagnose steatosis and are correlated with insulin resistance. They are confounded by fibrosis and inflammation, and do not accurately quantify steatosis; this may limit their clinical utility. More research is needed to identify truly independent and quantitative markers of steatosis.

Non-invasive score identifies ultrasonography-diagnosed non-alcoholic fatty liver disease and predicts mortality in the USA.

BackgroundSeveral non-invasive prediction scores for non-alcoholic fatty liver disease (NAFLD) have been developed, but their performance has not been compared and validated in the same population, and whether these prediction scores can predict clinical outcomes remains unknown. In this study, we aimed to validate and compare the performance of four NAFLD prediction scores: fatty liver index, hepatic steatosis index, lipid accumulation product, and NAFLD liver fat score (LFS), and to evaluate the ability of the best NAFLD prediction score to predict mortality.MethodsWe analyzed data from the National Health and Nutrition Examination Survey conducted in 1988 to 1994, and subsequent follow-up data for mortality up to December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases.ResultsIn a group of 5,184 participants, LFS consistently showed the highest area under the curve for predicting the presence of NAFLD. During a median follow-up of 14.7 years (range 0.1 to 18.2 years) and 83,830.5 person-years, participants in the high LFS group (LFS ≥1.257) had a higher cardiovascular and liver-related mortality than participants in the low (LFS ≤ −1.413; cardiovascular hazard ratio (HR) = 2.24, 95% CI 1.03 to 4.88; liver HR = 31.25, 95% CI 3.13 to 333.33) or intermediate (−1.413 < LFS < 1.257; cardiovascular HR = 2.3, 95% CI 1.19 to 4.48; liver HR = 30.3, 95% CI 4 to 250) LFS groups in the fully adjusted model. Similar results were obtained when LFS was treated as a continuous variable.ConclusionsLFS is the best non-invasive prediction score for NAFLD, and people with a high LFS score have an increased risk for cardiovascular and liver-related mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0154-x) contains supplementary material, which is available to authorized users.

A population-based study on the prevalence of NASH using scores validated against liver histology

Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. The population prevalence of NASH in 45-74 year old Finnish subjects is ∼ 5%.

The Effect of Helicobacter Pylori Eradication on Liver Fat Content in Subjects With Non-Alcoholic Fatty Liver Disease: A Randomized Open-Label Clinical Trial

BackgroundThe role of Helicobacter pylori (HP) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is unclear.ObjectivesThe aim of this study was to evaluate the effect of HP eradication on liver fat content (LFC), liver function tests (LFT), lipid profile, and homeostasis model assessment-IR (HOMA-IR) index in NAFLD.Patients and MethodsDyspeptic patients with increased serum aminotransferase levels were enrolled in the study. The exclusion criteria were factors affecting serum aminotransferase or HP treatment strategy. Participants with persistent elevated serum aminotransferase level and ultrasound criteria for identification of fatty liver were presumed to have NAFLD. “NAFLD liver fat score” was used to classify NAFLD. Those with “NAFLD liver fat score” greater than -0.64 and positive results for urea breath test (UBT), were included. Lifestyle modification was provided to all participants. HP eradication was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein (HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of eight weeks and twenty four weeks.ResultsOne hundred (49 males) patients with the mean age of 43.46 (± 11.52) were studied. Repeated measure ANOVA showed a significant reduction in LFC, anthropometric measurements, and laboratory parameters (except for HDL) in the both groups during the study; however, no significant difference was observed between the groups.ConclusionsIt seems that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin resistance in dyspeptic NAFLD patients.

Early growth and non-alcoholic fatty liver disease in adulthood—the NAFLD liver fat score and equation applied on the Helsinki Birth Cohort Study

Introduction. Prenatal and childhood growth influence the risk of developing the metabolic syndrome and type 2 diabetes. Both conditions are associated with non-alcoholic fatty liver disease (NAFLD). Our aim was to explore the associations between early growth and adult NAFLD.Methods. We studied 1587 individuals from the Helsinki Birth Cohort Study (HBCS) born 1934–44 for whom birth, childhood, and adult clinical data were available. NAFLD was defined using the NAFLD liver fat score and equation. The score was converted into a dichotomous variable, with outcomes defined as either a positive or negative score. The equation predicts liver fat percentage.Results. A positive score was found in 43% of men and 22.5% of women. Several measurements of birth and childhood body size were negatively associated with both NAFLD outcomes after adjustment for adult BMI. Those from the smallest BMI tertile at age 2 who were obese in adulthood had an OR of 18.5 for a positive score compared to those from the same group who were normal weight in adulthood.Conclusions. A larger childhood body size was negatively associated with NAFLD outcomes. Individuals who are small during early childhood and obese as adults seem to be at the highest risk of developing NAFLD.

The Effect of Pioglitazone and Metformin on Liver Function Tests, Insulin Resistance, and Liver Fat Content in Nonalcoholic Fatty Liver Disease: A Randomized Double Blinded Clinical Trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of insulin resistance (IR) syndrome. The effect of insulin sensitizers on liver function tests and metabolic indices in NAFLD patients is a matter of debate.ObjectivesThe aim of study was to compare the effects of two different insulin sensitizers, pioglitazone, and metformin, on liver function tests (LFT), lipid profile, homeostasis model assessment-IR (HOMA-IR) index, and liver fat content (LFC) in NAFLD patients.Materials and MethodsThis double blind clinical trial was performed on patients who were referred to a gastroenterology clinic with evidence of fatty liver in ultrasonography. After excluding other causes, participants with persistent elevated alanine aminotransferase (ALT) levels and “NAFLD liver fat score” greater than -0.64 were presumed to have NAFLD and were enrolled. They were randomly assigned to take metformin (1 g/day) or pioglitazone (30 mg/day) for four months. Fasting serum glucose (FSG), ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, cholesterol (CHOL), high and low density lipoprotein (HDL, LDL), HOMA-IR, and LFC were checked at the baseline, two and four months post-treatment. LFC was measured by a validated formula.ResultsEighty patients (68 males) with mean age of 35.27 (± 7.98) were included. After 2 months, LFT was improved significantly in the pioglitazone group and did not change in the metformin group. After four months, both medications significantly decreased serum levels of LFT, FSG, CHOL, LDL, HOMA-IR, and LFC, and increased serum level of HDL. No statistically significant differences were seen between the two treatment groups with regard to the changes of laboratory parameters and LFC from baseline to four months post-treatment.ConclusionsDuring the four months, the use of metformin (1 g/day) and pioglitazone (30 mg/day) were safe and might have equally affected LFT, HOMA-IR, lipid profile, and LFC in NAFLD patients.

Importance of liver fat indices for diagnosis of hepatic steatosis

Nonalcoholic fatty liver disease (NAFLD) strongly associates with obesity and type 2 diabetes and may lead to cirrhosis and hepatocellular carcinoma. Fatty liver indices based on laboratory and anthropometric parameters are increasingly used to predict steatosis in clinical studies, which requires solid validation. To this end, we examined the accuracy of three recently published indices – NAFLD liver fat score, fatty liver index and hepatic steatosis index – by comparison with exact quantification of liver fat content (HCL) by 1H-magnetic resonance spectroscopy (1H-MRS) in 92 non-diabetic humans (58 ± 12 years, BMI 26 ± 4 kg/m2). A 4-point 75-g oral glucose tolerance test was performed to assess insulin sensitivity and β-cell function. Employing 1H-MRS, 17 out of 92 subjects had fatty liver. HCL ranged from 0.03 to 39.01% with a median of 2.5 [0.6;4.2] and correlated with insulin sensitivity (composite whole body insulin sensitivity index, ISIcomp; r =-0.46, p < 0.001) and β-cell function (Disposition Index, DI; r = 0.36, p < 0.001). The tested indices yielded areas under the receiver operating curve (AROCs) from 0.70 to 0.79 and correlated with HCL (r = 0.40, 0.50 and 0.46, all p < 0.001), ISIcomp (r =-0.70, -0.62 and -0.53, all p < 0.001) and DI (r = 0.56, 0.47 and 0.48, all p < 0.001). Even after adjustments for age, sex and HCL, the indices remained independently associated with insulin sensitivity (β=-0.33, -0.19 and -0.04, all p < 0.001) and β cell function (β= 0.23, 0.13 and 0.03, all p < 0.001).

Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children

Accurate prediction scores for liver steatosis are demanded to enable clinicians to noninvasively screen for nonalcoholic fatty liver disease (NAFLD). Several prediction scores have been developed, however external validation is lacking. The aim was to determine the diagnostic accuracy of four existing prediction scores in severely obese children, to develop a new prediction score using novel biomarkers and to compare these results to the performance of ultrasonography. Liver steatosis was measured using proton magnetic resonance spectroscopy in 119 severely obese children (mean age 14.3 ± 2.1 years, BMI z-score 3.35 ± 0.35). Prevalence of steatosis was 47%. The four existing predictions scores ("NAFLD liver fat score," "fatty liver index," "hepatic steatosis index," and the pediatric prediction score) had only moderate diagnostic accuracy in this cohort (positive predictive value (PPV): 70, 61, 61, 69% and negative predictive value (NPV) 77, 69, 68, 75%, respectively). A new prediction score was built using anthropometry, routine biochemistry and novel biomarkers (leptin, adiponectin, TNF-alpha, IL-6, CK-18, FGF-21, and adiponutrin polymorphisms). The final model included ALT, HOMA, sex, and leptin. This equation (PPV 79% and NPV 80%) did not perform substantially better than the four other equations and did not outperform ultrasonography for excluding NAFLD (NPV 82%). The conclusion is in severely obese children and adolescents existing prediction scores and the tested novel biomarkers have insufficient diagnostic accuracy for diagnosing or excluding NAFLD.

Prediction of Non-Alcoholic Fatty Liver Disease and Liver Fat Using Metabolic and Genetic Factors

Our aims were to develop a method to accurately predict non-alcoholic fatty liver disease (NAFLD) and liver fat content based on routinely available clinical and laboratory data and to test whether knowledge of the recently discovered genetic variant in the PNPLA3 gene (rs738409) increases accuracy of the prediction. Liver fat content was measured using proton magnetic resonance spectroscopy in 470 subjects, who were randomly divided into estimation (two thirds of the subjects, n = 313) and validation (one third of the subjects, n = 157) groups. Multivariate logistic and linear regression analyses were used to create an NAFLD liver fat score to diagnose NAFLD and liver fat equation to estimate liver fat percentage in each individual. The presence of the metabolic syndrome and type 2 diabetes, fasting serum (fS) insulin, fS-aspartate aminotransferase (AST), and the AST/alanine aminotransferase ratio were independent predictors of NAFLD. The score had an area under the receiver operating characteristic curve of 0.87 in the estimation and 0.86 in the validation group. The optimal cut-off point of -0.640 predicted increased liver fat content with sensitivity of 86% and specificity of 71%. Addition of the genetic information to the score improved the accuracy of the prediction by only <1%. Using the same variables, we developed a liver fat equation from which liver fat percentage of each individual could be estimated. The NAFLD liver fat score and liver fat equation provide simple and noninvasive tools to predict NAFLD and liver fat content.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: assessment of non-invasive indices predicting hepatic steatosis and fibrosis.

Insulin resistance contributes to the pathogenesis of both polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). The main aim of the present study was the evaluation of non-invasive indices of hepatic steatosis and fibrosis in PCOS women with or without metabolic syndrome (MetS). In this cross-sectional study, three non-invasive indices for hepatic steatosis [NAFLD liver fat score, lipid accumulation product (LAP) and hepatic steatosis index (HIS)] and four for fibrosis [FIB-4, aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), body mass index (BMI)-Age-Alanine aminotransferase (ALT)-Triglycerides (BAAT) and BMI AST/ALT Ratio Diabetes (BARD)] were calculated in 314 PCOS women (77 with, 237 without MetS) and 78 controls. All steatosis indices were significantly higher in the PCOS than the control group (NAFLD liver fat score: -0.139 ± 0.117 vs. -0.976 ± 0.159, p<0.001; LAP: 43.3 ± 1.9 vs. 34.7 ± 3.1, p=0.036; HIS: 44.6 ± 0.5 vs. 42.1 ± 0.8, p=0.016). FIB-4 and BAAT [fibrosis stage (F)2-4] were higher in the PCOS group (0.480 ± 0.020 vs. 0.400 ± 0.013, p<0.001; and 15.6% vs. 5.1%, respectively), whereas APRI and BARD were not. All steatosis indices were significantly higher in PCOS women with than without MetS (NAFLD liver fat score: 1.874 ± 0.258 vs. -0.793 ± 0.099, p<0.001; LAP: 76.8 ± 4.9 vs. 33.4 ± 1.4, p<0.001; and HIS: 49.8 ± 1 vs. 43 ± 0.5, p<0.001). Of the fibrosis indices, only BAAT (F2-4: 50.6% vs. 4.2%) was higher in PCOS women with MetS. Non-invasive indices of hepatic steatosis were significantly higher in PCOS, especially in the presence of MetS, whereas indices of hepatic fibrosis yielded controversial results. Further studies are warranted to evaluate the long-term outcomes of hepatic steatosis and fibrosis indices in PCOS women.