Fatty Liver Disease Fibrosis Score Research Articles

Whole-liver histogram and texture analysis on T1 maps improves the risk stratification of advanced fibrosis in NAFLD

ObjectivesTo assess whole-liver texture analysis on T1 maps for risk stratification of advanced fibrosis in patients with suspected nonalcoholic fatty liver disease (NAFLD).MethodsThis retrospective study included 53 patients. Histogram and texture parameters (volume, mean, SD, median, 5th percentile, 95th percentile, skewness, kurtosis, diff-entropy, diff-variance, contrast, and entropy) of T1 maps were calculated based on the semi-automatically segmented whole-liver volume. A two-step approach combining the Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) and Fibrosis-4 Index (FIB-4) with the liver stiffness measurement (LSM) for the risk stratification was used. Univariate analysis was performed to identify significant parameters. Logistic regression models were then run on the significant features. Diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis.ResultsIn total, 33 (62%) subjects had a low risk and 20 (38%) subjects had an intermediate-to-high risk of advanced fibrosis. The following significantly different parameters with the best performance were diff-entropy, entropy, and diff-variance, with AUROC 0.837 (95% CI 0.73–0.95), 0.821 (95% CI 0.71–0.94), and 0.807 (95% CI 0.69–0.93). The optimal combination of median, 5th percentile, and diff-entropy as a multivariate model improved the diagnostic performance to diagnose an intermediate-to-high risk of advanced fibrosis with AUROC 0.902(95% CI 0.79–0.97).ConclusionsParameters obtained by histogram and texture analysis of T1 maps may be a noninvasive analytical approach for stratifying the risk of advanced fibrosis in NAFLD.Key Points• Variable flip angle (VFA) T1 mapping can be used to acquire 3D T1 maps within a clinically acceptable duration.• Whole-liver histogram and texture parameters on T1 maps in patients with NAFLD can distinguish those with an intermediate-to-high risk of advanced fibrosis.• The multivariate model of combination of texture parameters improved the diagnostic performance for a high risk of advanced fibrosis and clinical parameters offer no added value to the multivariate model.

THU003 - Non-alcoholic fatty liver disease fibrosis score predicts cardiovascular mortality in post percutaneous coronary intervention patients: 5-year results from an observational registry

THU003 - Non-alcoholic fatty liver disease fibrosis score predicts cardiovascular mortality in post percutaneous coronary intervention patients: 5-year results from an observational registry

Issue Highlights

Issue Highlights

Association between steatohepatitis biomarkers and hepatocellular carcinoma after hepatitis C elimination.

A strong association between chronic hepatitis C (CHC) and hepatic steatosis has been reported. However, the influence of steatohepatitis on hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) elimination remains unclear. To evaluate the development of HCC after HCV cure using a new steatohepatitis-related biomarker. This cohort study analysed the prospective database of 290 CHC patients without a history of HCC who achieved HCV elimination by direct-acting antivirals. We calculated the FibroScan-aspartate aminotransferase (FAST) score 12weeks after the end of treatment (pw12). The risk of HCC was analysed using the multivariable Cox proportional hazard model. HCV genotype (GT)1 was most prevalent at 72.4%, followed by GT2 (26.6%). Median follow-up period was 4.2years (IQR 3.1-4.5). The cumulative HCC incidence for a FAST score≥0.35 was significantly higher than that for a FAST score<0.35 (log-rank test: P<0.001). The annual HCC incidence rate for a FAST score≥0.35 was significantly higher than that for a FAST score<0.35, in patients with liver stiffness measurement (LSM) ≥10kPa (adjusted hazard ratio [HR] 4.41, 95% confidence interval [CI] 1.30-15.0, P=0.018). After adjusting for variables, including age, albumin, alpha-fetoprotein, the patatin-like phospholipase domain-containing the 3 (PNPLA3) rs738409 genotype, and pw12 fibrosis markers with FIB-4, non-alcoholic fatty liver disease fibrosis score, and LSM, FAST score≥0.35 was associated with the development of HCC (adjusted HR 4.42, 95% CI 1.02-19.9, P=0.043). Steatohepatitis-related biomarkers with the FAST score are helpful for predicting the development of HCC after HCV elimination.

Gemcabene as a Potential Therapeutic for NASH: Lessons Learnt from its Clinical Trials in Dyslipidemia

Elevated hepatic lipogenesis and inflammation are associated with the progression of non-alcoholic steatohepatitis (NASH) and cardiovascular disease. Gemcabene, a small molecule in development for dyslipidemia, reduces plasma very low-density lipoprotein cholesterol (VLDL-C), lowdensity lipoprotein cholesterol (LDL-C), triglycerides (TG) and C-reactive protein (CRP) in animal models and humans. An analysis of the clinical information available for gemcabene and translational research substantiates the potential of gemcabene as a therapeutic agent for NASH. Specifically, gemcabene showed positive effects in clinical trials in severe hypertriglyceridemia and in subsets of obese, diabetic patients, particularly reductions in triglycerides, cholesterol and proatherogenic and inflammation markers. In nonclinical models, gemcabene showed significant improvement in non-alcoholic fatty liver disease (NAFLD) activity and fibrosis scores and affected beneficially the hepatic expression of many lipid regulating and inflammatory genes.

The diagnostic utility of fibrosis-4 or nonalcoholic fatty liver disease fibrosis score combined with liver stiffness measurement by fibroscan in assessment of advanced liver fibrosis: a biopsy-proven nonalcoholic fatty liver disease study

The clinical guidelines recommend the use of nonalcoholic fatty liver disease fibrosis score and fibrosis-4 score for estimating the advanced liver fibrosis in nonalcoholic fatty liver disease. However, these scores are used confidently in eliminating advanced fibrosis, rather than detecting it. Therefore, paired combination with liver stiffness measurement by transient elastography is recommended. In this study, we aimed to validate this combined algorithm in our study population. A total of 139 consecutive biopsy-proven nonalcoholic fatty liver disease patients were enrolled in the study. We calculated the noninvasive scores and performed liver stiffness measurement examination for each patient. The optimal cutoff of liver stiffness measurement for advanced fibrosis was 11.0 kPa (area under curve: 0.856) with a sensitivity of 84% and a specificity of 78%. Using the fibrosis-4 score (< 1.45 for low risk of advanced fibrosis and > 3.25 for high risk of advanced fibrosis) in combination with the liver stiffness measurement cutoffs revealed the best diagnostic performance (< 8.8 kPa for low risk of advanced fibrosis and > 10.9 kPa for high risk of advanced fibrosis). This paired combination had the positive predictive value of 0.735 at a sensitivity of 89% and the negative predictive value of 0.932 at a specificity of 82%. A paired combination of the fibrosis-4 score and liver stiffness measurement (< 8.8 kPa for exclusion of advanced fibrosis and > 10.9 kPa for inclusion of advanced fibrosis) is able to diagnose the patients with advanced fibrosis with the highest diagnostic accuracy.

Intragastric Balloon Placement Induces Significant Metabolic and Histologic Improvement in Patients With Nonalcoholic Steatohepatitis

Obese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. Twenty-one patients with early hepatic fibrosis (81% female; mean age, 54 years; average body mass index, 44 kg/m2) underwent magnetic resonance elastography (MRE) and endoscopic ultrasound with core liver biopsy collection at time IGB placement and removal at a single center from October 2016 through March 2018. The primary outcome measure was the changes in liver histology parameters after IGB, including change in nonalcoholic fatty liver disease activity score (NAS) and fibrosis score. We also evaluated changes in weight, body mass index, waist to hip ratio, aminotransaminases, fasting levels of lipids, fasting glucose, glycosylated hemoglobin, and MRE-detected liver stiffness. Six months after IGB, patients' mean total body weight loss was 11.7% ± 7.7%, with significant reductions in HbA1c (1.3% ± 0.5%) (P = .02). Waist circumference decreased by 14.4 ± 2.2 cm (P = .001). NAS improved in 18 of 20 patients (90%), with a median decrease of 3 points (range, 1-4 points); 16 of 20 patients (80%) had improvements of 2 points or more. Fibrosis improved by 1.17 stages in 15% of patients, and MRE-detected fibrosis improved by 1.5 stages in 10 of 20 patients (50%). Half of patients reached endpoints approved by the Food and Drug Administration of for NASH resolution and fibrosis improvement. Percent total body weight loss did not correlate with reductions in NAS or fibrosis. Other than post-procedural pain (in 5% of patients), no serious adverse events were reported. In a prospective study, IGB facilitated significant metabolic and histologic improvements in NASH. IGB appears to be safe and effective for NASH management when combined with a prescribed diet and exercise program. ClinicalTrials.gov no: NCT02880189.

The Prevalence of NAFLD and Fibrosis in Bariatric Surgery Patients and the Reliability of Noninvasive Diagnostic Methods.

Background Bariatric surgery patients have a higher prevalence of nonalcoholic fatty liver (NAFL) than the general population; however, its assessment and the accurate staging of fibrosis are often complicated because noninvasive tests are not very accurate in patients with morbid obesity, and liver biopsy cannot be performed as a routine exam. The aim of this study was to evaluate (A) the histological prevalence of NAFL, nonalcoholic steatohepatitis (NASH), and fibrosis in patients undergoing bariatric surgery; (B) the reliability of ultrasound (US) in diagnosing NAFL; and (C) the reliability of various fibrosis scoring systems for defining fibrosis. Methods US and intraoperative liver biopsy results were reviewed in 57 bariatric surgery patients. NAFL, NASH, and fibrosis were diagnosed according to the Kleiner scoring system. US diagnosis of liver steatosis was based on the bright liver. Fibrosis scores used were (i) the BMI, AST/ALT Ratio, Diabetes (BARD) scoring system; (ii) the nonalcoholic fatty liver disease (NAFLD) fibrosis score; and (iii) the fibrosis-4 (FIB-4) index. Results The prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94% (F3 5.7%, cirrhosis 2.8%). The sensitivity of US was 95%, specificity 50%, and likelihood ratio (LR+, LR-) 1.91 and 0.1. The reliability of fibrosis scores for F ≥ 2 were as follows: BARD score: sensitivity 46%, specificity 54%, and area under the receiver-operating characteristics (AUROC) curve 0.5; NAFLD score: sensitivity 30%, specificity 89%, and AUROC 0.5; and FIB-4: sensitivity 68%, specificity 67%, and AUROC 0.7. Conclusions In bariatric surgery patients, the prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94%. US is able to rule out the presence of NAFL, while the commonly used scores may be inaccurate in defining fibrosis in patients with morbid obesity.

The Association between Non-Alcoholic Fatty Liver Disease Fibrosis Score and Serum Low Density Lipoprotein-Cholesterol Levels in Adults with Non-Alcoholic Fatty Liver Disease

The Association between Non-Alcoholic Fatty Liver Disease Fibrosis Score and Serum Low Density Lipoprotein-Cholesterol Levels in Adults with Non-Alcoholic Fatty Liver Disease

Insulin resistance is related with liver fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease proven biopsy and Mediterranean diet pattern as a protective factor.

The prevalence of the non-alcoholic fatty liver disease (NAFLD) in developed countries is up to 30% of the general population, and 50% of patients present type 2 diabetes mellitus (DM2). Fibrosis is the most important prognostic factor in NAFLD. The aim of this study was to search evidence for an early diagnosis of liver fibrosis in subjects with DM2 and to evaluate potential risk and protective factors. This study was conducted among 160 diabetic patients with NAFLD proven biopsy. Anthropometric assessments, laboratory test, liver histological features and follow-up of a Mediterranean diet were evaluated. Diabetic patients with liver fibrosis showed a greater number of positive metabolic criteria than diabetic patients without liver fibrosis. Patients with hepatic fibrosis have a lower score on the PREDIMED test (9.0 (2.4) vs. 6.2 (2.3); p < 0.05). Diabetic patients with liver fibrosis showed higher glucose levels (delta: 10.1 (4.5) mg/dl), fasting insulin levels (delta: 3.1 (1.5) UI/L), HOMA-IR (delta: 2.1 (0.3) units) and HbA1c (delta: 0.6 (0.2)%). Non-invasive tests showed a higher score (non-alcoholic fatty liver disease fibrosis score and fibrosis-4) in liver fibrosis subjects than no liver fibrosis subjects. A logistic regression analysis adjusted by age, gender, HbA1c and body mass index showed independent significant direct association between liver fibrosis and homeostatic model assessment of insulin resistance as indicator of insulin resistance (odds ratio (OR) = 1.53: 95% confidence interval (CI): 1.1-2.2; p = 0.026) and inverse association with PREDIMED score as an indicator of adherence to Mediterranean diet (OR = 0.6; 95% CI: 0.4-0.8; p = 0.01). In patients with DM2, insulin resistance is an independent risk factor associated with liver fibrosis, and the adherence of a Mediterranean diet is a protective factor associated with absence of liver fibrosis.

Association between liver fibrosis scores and the risk of mortality among patients with coronary artery disease

Background and aimsFatty liver diseases are highly prevalent in patients with coronary artery disease (CAD) and might progress to irreversible liver fibrosis. Whether baseline liver fibrosis (LF) scores are associated with long-term mortality among patients with CAD requires investigation. MethodsThe analysis was conducted based on a prospective cohort study among 3263 patients with CAD in China. Cox models were used to assess the association of baseline levels of LF scores, including non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 score (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyltransferase to platelet ratio (GPR), and Forns score, with the risk of all-cause and cardiovascular mortality among CAD patients. ResultsDuring a median follow-up period of 7.56 (inter-quartile range: 6.86–8.31) years, 538 deaths were identified, 319 of those were due to cardiovascular diseases. Compared with patients with lowest score levels, multivariable-adjusted HRs (95% CI) for those with highest levels of NFS, FIB-4, APRI, GPR and Forns score were 2.89 (2.14–3.91), 2.84 (2.14–3.76), 1.77 (1.33–2.36), 1.47 (1.19–1.83) and 3.10 (1.88–5.11) for all-cause mortality, 3.02 (2.05–4.45), 3.34 (2.29–4.86), 1.99 (1.40–2.83), 1.80 (1.36–2.39) and 2.43 (1.28–4.61) for cardiovascular mortality, respectively. These associations were consistent when we excluded those who died within the first year of follow-up or stratified patients by different sex, age, BMI, diabetes status, metabolic syndrome status, CAD type and hsCRP level. ConclusionsHigher LF scores are associated with increased risks of all-cause and cardiovascular mortality among CAD patients. LF scores might play a potential role in CAD prognosis prediction.

Accuracy of Noninvasive Fibrosis Scores to Detect Advanced Fibrosis in Patients With Type-2 Diabetes With Biopsy-proven Nonalcoholic Fatty Liver Disease.

Recent guidelines have recommended screening for nonalcoholic fatty liver disease (NAFLD) and case finding of advanced disease with fibrosis in patients with type-2 diabetes (T2D). The aim of this study is to assess the accuracy of commonly used noninvasive scores to predict the presence of advanced fibrosis (AF) in a large cohort of diabetics in real-life settings. Using International Classification of Diseases, Ninth Revision (ICD-9) codes, all patients with the diagnosis of T2D who had a liver biopsy for suspected NAFLD between January 2000 and December 2015, were identified and analyzed. Patients with secondary causes of hepatic steatosis were excluded. AST/ALT ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and Nonalcoholic fatty liver disease Fibrosis Score (NFS) were calculated to predict advanced disease. Sensitivity, specificity, and area under the receiver operator curve were calculated and compared with liver biopsies to predict the overall accuracy of each score. A total of 1319 patients with T2D underwent liver biopsy for suspected NAFLD. After exclusions, 1,157 subjects were included in the final analysis. Our cohort consisted of 64.6% females and 88.4% were whites. Overall, 85% of the population was overweight or obese (body mass index>25 kg/m). Liver biopsy showed 31.7% with AF [Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) stage 3 to 4]. In comparison to liver biopsy, for the diagnosis of AF, AST/ALT>1.4, APRI>1.5, FIB-4>2.67, and NFS>0.676 had reasonable specificities of 84.2%, 97.4%, 69.9%, and 93% but poor sensitivities of 27.4%, 16.5%, 6.7%, and 44.1%, respectively. Even at lower cutoff values of AST/ALT≥1, APRI≥1, and FIB-4≥1.45 sensitivities remained low at 60.7%, 27.9%, and 72.6%, respectively, except for NFS ≥-1.455 with sensitivity of 94.6%, but at this cutoff, its specificity decreased to 16.9%. The area under the receiver operator curve to detect AF was 0.62, 0.74, 0.77, and 0.72, respectively. In this large cohort of adult patients with T2D and NAFLD, commonly used fibrosis scores had reasonable specificity, but poor sensitivity for detecting AF in diabetics. The development of reliable biomarkers for NAFLD/NASH in diabetics is urgently needed.

A188 COMPARING THE PERFORMANCE OF FIBROSIS-4 (FIB-4) AND NON-ALCOHOLIC FATTY LIVER DISEASE FIBROSIS SCORE (NFS) WITH FIBROSCAN SCORES IN NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract Background With the rates of non-alcoholic fatty liver disease (NAFLD) on the rise, the necessity of identifying patients at risk of cirrhosis and its complications is becoming ever more important. Liver biopsy remains the gold standard for assessing fibrosis, although the costs, risks, and availability prohibit its widespread use for at-risk patients. Fibroscan has proven to be a non-invasive and accurate way of assessing fibrosis, although the availability of this modality is often limited in the primary care setting. The Fibrosis-4 (FIB-4) and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) are scoring systems which incorporate commonly measured lab parameters and BMI to predict fibrosis. In this study, we compared FIB-4 and NFS values to fibroscan scores to assess the accuracy of these inexpensive and readily available scoring systems for detecting fibrosis. Aims The aim of this study was to determine if non-invasive and inexpensive scoring systems (FIB-4 and NFS) can be used to rule out fibrosis in non-alcoholic fatty liver disease with comparable efficacy to fibroscan. Ultimately, we aim to demonstrate that these scoring systems can be used as an alternative to fibroscan in some patients. Methods Data was collected from 317 patient charts from the Vancouver General Hepatology Clinic. 93 patients were removed from the study due to insufficient data (missing Fibroscan score or lab work necessary for FIB-4/NFS). For the remaining 224 patients, FIB-4 and NFS were calculated and compared to fibrosis scores both independently and in combination. Results: Using a NFS score cut-off of -1.455 and a fibroscan score cut-off of ≥8.7kPa, the NFS had a sensitivity of 71.9%, a specificity of 75%, and a negative predictive value of 94.1%. For a fibroscan score cut-off of ≥8.0kPa, the NFS had a sensitivity of 66.7%, a specificity of 75.7%, and a negative predictive value of 91.5%. Using a fibroscan score cut-off of ≥8.7kPa, the FIB-4 score had a sensitivity of 53.1%, specificity of 84.9%, and a negative predictive value of 91.6%. For a cut-off of ≥8.0kPa, it had a sensitivity of 51.3%, and 85.9%, and a negative predictive value of 89.3%. Conclusions: The NFS and FIB-4 are non-invasive scoring systems that have high sensitivity and negative predictive value for fibrosis when compared to fibroscan scores. These findings suggest that the NFS and FIB-4 can provide adequate reassurance to rule-out fibrosis in select patients, and has promising use in the primary care setting where fibroscan access is often limited. Funding Agencies None

Liver Fibrosis Indices and Outcomes After Primary Intracerebral Hemorrhage.

Background and Purpose- Cirrhosis-clinically overt, advanced liver disease-is associated with an increased risk of hemorrhagic stroke and poor stroke outcomes. We sought to investigate whether subclinical liver disease, specifically liver fibrosis, is associated with clinical and radiological outcomes in patients with primary intracerebral hemorrhage. Methods- We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-Intracerebral Hemorrhage. We included adult patients with primary intracerebral hemorrhage presenting within 6 hours of symptom onset. We calculated 3 validated fibrosis indices-Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4 score, and Nonalcoholic Fatty Liver Disease Fibrosis Score-and modeled them as continuous exposure variables. Primary outcomes were admission hematoma volume and hematoma expansion. Secondary outcomes were mortality, and the composite of major disability or death, at 90 days. We used linear and logistic regression models adjusted for previously established risk factors. Results- Among 432 patients with intracerebral hemorrhage, the mean Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4, and Nonalcoholic Fatty Liver Disease Fibrosis Score values on admission reflected intermediate probabilities of fibrosis, whereas standard hepatic assays and coagulation parameters were largely normal. After adjusting for potential confounders, Aspartate Aminotransferase-Platelet Ratio Index was associated with hematoma volume (β, 0.20 [95% CI, 0.04-0.36]), hematoma expansion (odds ratio, 1.6 [95% CI, 1.1-2.3]), and mortality (odds ratio, 1.8 [95% CI, 1.1-2.7]). Fibrosis-4 was also associated with hematoma volume (β, 0.27 [95% CI, 0.07-0.47]), hematoma expansion (odds ratio, 1.9 [95% CI, 1.2-3.0]), and mortality (odds ratio, 2.0 [95% CI, 1.1-3.6]). Nonalcoholic Fatty Liver Disease Fibrosis Score was not associated with any outcome. Indices were not associated with the composite of major disability or death. Conclusions- In patients with largely normal liver chemistries, 2 liver fibrosis indices were associated with admission hematoma volume, hematoma expansion, and mortality after intracerebral hemorrhage.

Effective Detection of Compensated Cirrhosis Using Machine Learning

Background: Cirrhosis is often diagnosed once complications such as ascites, encephalopathy and variceal bleeding have occurred. Current non-invasive tests to detect cirrhosis have limited performance, with many patients falling into the indeterminate category. Objectives: To identify patients with well-compensated liver cirrhosis of all-causes using machine learning algorithms (MLAs) trained on routinely measured clinical and laboratory parameters. Design, Setting, and Participants: Retrospective, cross-sectional study on patients with F0, F1, and F4 fibrosis staged via biopsy at the Toronto Liver Clinic, validated on 508 patients with F0 to F4 fibrosis staged via biopsy locally as well as at the McGill University Health Centre. Patients with decompensated cirrhosis were excluded. We trained 7 MLAs to identify patients with compensated cirrhosis. Performance was benchmarked against the Aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), Fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), Transient Elastography (TE), and an independent panel of 5 experts. Results: The best MLA achieved a cross-validation area under the receiver operating characteristic curve (AUROC) of 0.88 for identifying patients with well-compensated cirrhosis, with less than 8% indeterminate classifications. The MLA achieved higher or comparable AUROC to FIB-4 on both validation sets with 20% fewer indeterminate classifications. Additionally, we show that by altering cutoffs, the MLA outperformed expert hepatologists and the NFS score and achieved superior specificity to transient elastography. Conclusion: In this study, we have demonstrated that an MLA outperforms non-imaging based methods in detecting well-compensated cirrhosis across multiple etiologies of liver disease. Our MLA was superior to APRI, FIB-4, and NFS with significantly fewer indeterminate classifications, while achieving performance comparable to an independent panel of experts. MLAs using routinely collected data could flag patients with well-compensated liver cirrhosis among patients with chronic liver disease, allowing intervention prior to onset of decompensation and associated complications. Funding Statement: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Declaration of Interests: We have no competing interests to declare. Ethics Approval Statement: Ethics approval was obtained from the Research Ethics Boards at the University Health Network, SickKids Research Institute, and MUHC.

Clinical utility of noninvasive scores in assessing advanced hepatic fibrosis in patients with type 2 diabetes mellitus: a study in biopsy-proven non-alcoholic fatty liver disease.

Simple noninvasive fibrosis scores based on routine blood tests have been increasingly investigated as screening tools in different clinical settings. Here, we sought to examine whether the Fibrosis-4 Index (FIB-4) and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) could perform differently in diabetic versus non-diabetic patients with biopsy-proven NAFLD. We examined 349 patients with biopsy-proven NAFLD (166 with type 2 diabetes and 183 without). Patients with FIB-4 scores < 1.3 and > 2.67 or NFS scores < - 1.455 and > 0.676 were considered at low and high risk of advanced fibrosis, respectively. A FIB-4 cutoff value of 1.3-which denotes a low risk of advanced fibrosis-had a specificity of 67% in patients with diabetes and 69% in those without. Conversely, a FIB-4 cutoff value of 2.67-which denotes a high risk of advanced fibrosis-had a sensitivity of 22% in patients with diabetes and 0% in those without. NFS performed similar to FIB-4. Both FIB-4 and NFS scores have an acceptable clinical utility in the exclusion of advanced fibrosis in patients with NAFLD, regardless of the presence of type 2 diabetes. However, their usefulness in identifying advanced fibrosis is limited-especially in the absence of diabetes.

Correlation between nonalcoholic fatty liver disease fibrosis score and unstable plaques of carotid in elderly patients with nonalcoholic fatty liver disease

Objective To investigate the correlation between nonalcoholic fatty liver disease(NAFLD)fibrosis score(NFS)and unstable plaques of carotid in elderly NAFLD patients. Methods The clinical and carotid plaques data of 191 elderly(≥60 years old)admitted into our department between July 2016 and January 2018 were retrospectively collected.With NFS 0.676 as a cut-off point, the patients were divided into a liver fibrosis group(NFS ≥0.676, n=65)and a non-liver fibrosis group(NFS<0.676, n=126). Based on quartiles of NFS, the patients were divided into four groups: the Q1 group(NFS<-0.865, n=48), the Q2 group(-0.865≤NFS<0.100, n=48), the Q3 group(0.1≤NFS<1.070, n=47), the Q4 group(NFS≥1.070, n=48). The correlation of NFS with the property of carotid plaques was analyzed. Results The detection rate of unstable carotid plaques was increased along with the increase of NFS(F=8.573, P=0.004). The detection rate of unstable carotid plaques was higher in the liver fibrosis group than in the non-liver fibrosis group(78.5% or 51/65 vs.60.3% or 76/126, χ2=5.883, P=0.015). Multiple logistic regression analysis showed that liver fibrosis(NFS≥0.676)was independently correlated with unstable carotid plaques(β=0.816, 95%CI: 1.110~4.607, OR=2.261, P=0.025)after adjusting for possible confounding factors including age, gender, diabetes mellitus, hypertension, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein. Conclusions NFS is correlated with unstable carotid plaques in elderly NAFLD patients, and the higher NFS is the independent risk factor for unstable carotid plaques for elderly NAFLD patients with NFS higher than 0.676.We should pay more attention to the evaluation of unstable carotid plaques. Key words: Fatty liver; Liver cirrhosis; Carotid arteries

Poor Concordance Between Liver Stiffness and Noninvasive Fibrosis Scores in HIV Infection Without Viral Hepatitis

People living with human immunodeficiency virus (PLWH) are at higher risk of liver fibrosis compared with the general population. As liver fibrosis is independently associated with poor long-term liver related outcomes and mortality,1 early detection is extremely important. Liver biopsy is considered gold standard for the diagnosis of liver fibrosis. However, this invasive procedure is only suitable for a selected group of patients because of the risk of serious complications. We aimed to estimate the concordance between vibration-controlled transient elastography (VCTE) and simple noninvasive liver fibrosis scores-Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), and nonalcoholic fatty liver disease fibrosis score (NFS)-in PLWH without viral hepatitis.

P737Endothelial ERK2/thromboxane receptor pathway induces endothelial dysfunction, insulin resistance and steatohepatosis through superoxide with high fat high sucrose diet

Abstract Introduction Metabolic syndrome (MetS) is well known as the risk of cardiovascular diseases associated with endothelial dysfunction and induces steatohepatosis. Insulin resistance is a major character of MetS, which affects intracellular signaling pathways and endothelial function. Extracellular signal-regulated kinase (ERK) is a major component of insulin signal and many of vasoactive peptides, which were released in MetS, can activate it in endothelium. However, the role of endothelial ERK in nitric oxide (NO) bioactivity in MetS in in vivo has been unknown. Purpose The aim of this study is to clarify the role of endothelial ERK2 on NO bioactivity in mice model of MetS. Methods and results We created endothelial specific ERK2 knock out mice (EE2KO) crossing Tie2-Cre mice and ERK2 flox mice and fed them with normal or high-fat/high-sucrose diet (HFHSD) for 24 weeks. Serum glucose and insulin levels and HOMA-IR were lowered in EE2KO with HFHSD without changing body weight. In wild type mice (WT) with HFHSD, nonalcoholic fatty liver disease (NAFLD) activity score, fibrosis score and serum ALT level were increased, all of which were blunted in EE2KO. EE2KO with HFHSD lowered systolic blood pressure (WT: 123.7±5.83 mmHg, EE2KO: 101.4±3.66 mmHg, P&lt;0.01, N=8) without changing heart rate, which was increased to the same levels with L-NAME, an endothelial NO synthase inhibitor, in both groups. Serum NO levels measured with serum nitrite/nitrate concentrations were increased in EE2KO with HFHSD (WT: 23.10±3.74 μmol/l, EE2KO: 41.71±6.73 μmol/l, P&lt;0.05, N=12). Endothelial function was assessed with the isometric tension measurement of aortic rings with acetylcholine (ACh). ACh-induced relaxation was improved in EE2KO with HFHSD. Superoxide production of aorta from EE2KO was lowered than WT with HFHSD in dihydroethidium (DHE) staining. S18886, an antagonist of the thromboxane A2-prostanoid (TP) receptor, decreased superoxide production of aorta in DHE staining resulting in improving endothelial function in the isometric tension measurement of aortic rings. Oral administrations of S18886 decreased systolic blood pressure, serum fasting glucose and insulin levels, and surprisingly improved steatohepatosis by decreasing NAFLD activity score and fibrosis score. Relaxation of aortic rings with ACh Conclusions Endothelial ERK2/TP receptor pathway increases superoxide production and decreased NO bioactivity, resulting in deteriorating endothelial function, insulin resistance and steatohepatosis, which were improved by antagonist of the TP receptor in mice model of MetS. The present study indicates that ERK2/TP pathway could be a therapeutic target for complications of MetS.

Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease

Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n= 127,302), BARD (n= 75,303), FIB-4 (n= 126,941), Forns (n= 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n= 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine whichscoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patientswere followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.