Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease

AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden’s index.RESULTS: The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden’s index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden’s index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Effect of Compound 962 Capsule on Liver Lipid Peroxidation and Indexes of Thymus Gland and Spleen in Rats

Objective: To investigate the effect of compound 962 capsule (abbre. as 962) on liver lipid peroxidation and indexes of thymus and spleen in aged rats. Methods: Rats were divided into young control, aged model, Piracetam, 962 middle dose (0.9 g/kg) and high dose (1.8 g/kg) groups. All test drugs were administrated for 1 month by gastrogavage. The liver lipid peroxidation was determined by thiobarbituric (TBA) method. The thymus index and spleen index were determined by weighing method. Results: 962 (middle and high dose) attenuated liver lipid peroxidation, increased the thymus index of aged rats. There was no effect on spleen index in all drug-treated groups. Conclusion: 962 could decrease liver lipid peroxidation and increase thymus index. It suggested that 962 might be beneficial in retarding aging process.

Liver Fat Scores for Noninvasive Diagnosis and Monitoring of Nonalcoholic Fatty Liver Disease in Epidemiological and Clinical Studies

Nonalcoholic fatty liver disease(NAFLD)is strongly associated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term complications.Being often asymptomatic but reversible,it would require population-wide screening,but direct diagnostics are either too invasive(liver biopsy),costly(MRI)or depending on the examiner’s expertise(ultrasonography).Hepatosteatosis is usually accommodated by features of the metabolic syndrome(e.g.obesity,disturbances in triglyceride and glucose metabolism),and signs of hepatocellular damage,all of which are reflected by biomarkers,which poorly predict NAFLD as single item,but provide a cheap diagnostic alternative when integrated into composite liver fat indices.Fatty liver index,NAFLD LFS,and hepatic steatosis index are common and accurate indices for NAFLD prediction,but show limited accuracy for liver fat quantification.Other indices are rarely used.Hepatic fibrosis scores are commonly used in clinical practice,but their mandatory reflection of fibrotic reorganization,hepatic injury or systemic sequelae reduces sensitivity for the diagnosis of simple steatosis.Diet-induced liver fat changes are poorly reflected by liver fat indices,depending on the intervention and its specific impact of weight loss on NAFLD.This limited validity in longitudinal settings stimulates research for new equations.Adipokines,hepatokines,markers of cellular integrity,genetic variants but also simple and inexpensive routine parameters might be potential components.Currently,liver fat indices lack precision for NAFLD prediction or monitoring in individual patients,but in large cohorts they may substitute nonexistent imaging data and serve as a compound biomarker of metabolic syndrome and its cardiometabolic sequelae.

A novel model for predicting fatty liver disease by means of an artificial neural network

Background:The artificial neural network(ANN)emerged recently as a potent diagnostic tool,especially for complicated systemic diseases.This study aimed to establish a diagnostic model for the recognition of fatty liver disease(FLD)by virtue of the ANN.Methods:A total of 7,396 pairs of gender-and age-matched subjects who underwent health check-ups at the First Affiliated Hospital,College of Medicine,Zhejiang University(Hangzhou,China)were enrolled to establish the ANN model.Indices available in health check-up reports were utilized as potential input variables.The performance of our model was evaluated through a receiver-operating characteristic(ROC)curve analysis.Other outcome measures included diagnostic accuracy,sensitivity,specificity,Cohen’s k coefficient,Brier score,and Hosmer-Lemeshow test.The Fatty Liver Index(FLI)and the Hepatic Steatosis Index(HSI),retrained using our training-group data with its original designated input variables,were used as comparisons in the capability of FLD diagnosis.Results:Eight variables(age,gender,body mass index,alanine aminotransferase,aspartate aminotransferase,uric acid,total triglyceride,and fasting plasma glucose)were eventually adopted as input nodes of the ANN model.By applying a cut-off point of 0.51,the area under ROC curves of our ANN model in predicting FLD in the testing group was 0.908[95%confidence interval(CI),0.901-0.915]—significantly higher(P<0.05)than that of the FLI model(0.881,95%CI,0.872-0.891)and that of the HSI model(0.885;95%CI,0.877-0.893).Our ANN model exhibited higher diagnostic accuracy,better concordance with ultrasonography results,and superior capability of calibration than the FLI model and the HSI model.Conclusions:Our ANN system showed good capability in the diagnosis of FLD.It is anticipated that our ANN model will be of both clinical and epidemiological use in the future.

Discrepancies between Nonalcoholic and Metabolic-associated Fatty Liver Disease by Multiple Steatosis Assessment

Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain unclear.The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.Methods:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020.Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave elastography.Results:The study enrolled 14,985 Chi-nese adults.The agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver biopsy.The body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.Conclusions:The new MAFLD definition ruled out 5-17%of NAFLD cases.NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD.Non-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal range.Attention should be paid to its progression.

Non-alcoholic fatty liver disease:a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines

Non-alcoholic fatty liver disease(NAFLD)is among the most frequently encountered chronic liver diseases in everyday clinical practice.It is considered the hepatic manifestation of metabolic syndrome.Today,liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD’s possible progression to non-alcoholic steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures,it is of great interest to recruit the patients for liver biopsy.However,as the presence of liver fibrosis determines the further clinical course,liver biopsy is expectedly reserved for those with increased fibrosis risk.The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners,gastroenterologists,and endocrinologists.As a result,the quality of liver biopsy recruitment and patients monitoring could be significantly improved.Here,we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients.

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.