Fatty Liver Disease Fibrosis Score Research Articles

Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis.

Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood. Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30IU/L for men and >19IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score. Of the 6738 participants (mean age 46.3years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively). In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors.

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe

ObjectiveThe nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. MethodsWe applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. ResultsAmong 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19–1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74–0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91–1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < −1.455 = 1.55 [1.32–1.81]; p < 0.001). ConclusionStratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy.Clinical trials.gov: NCT00202878.

Nonalcoholic fatty liver disease is associated with decreased lung function.

The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross-sectional and longitudinal analysis. Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3years' follow-up were included. In cross-sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching. Of 11892 eligible participants (mean age, 47.7years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross-sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1-second (men, 3.52 vs 3.44L, P<.001; women, 2.62 vs 2.45L, P<.001) and forced vital capacity (men, 4.33 vs 4.24L, P<.001; women, 3.11 vs 2.97L, P<.001) than the control group. In longitudinal analysis, during the mean follow-up period of 6.6years, there were no significant differences in forced expiratory volume in 1-second or forced vital capacity decline rates between two groups in the propensity score-matched cohorts (n=4558). However, those with high nonalcoholic fatty liver disease fibrosis score and fibrosis-4 (men, -21.7 vs -27.4mL/y, P=.001; women, -22.4 vs -27.9mL/y, P=.016) showed significantly faster decline in forced vital capacity compared to those with low scores. Nonalcoholic fatty liver disease was associated with decreased lung function at baseline but was not associated with accelerated lung function decline in the propensity score-matched cohort. However, hepatic fibrosis was significantly associated with rapid forced vital capacity decline.

FRI-450 - Temporal assessment of the non-invasive fibrosis scores FIB-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) in a retrospective cohort study among patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

FRI-450 - Temporal assessment of the non-invasive fibrosis scores FIB-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) in a retrospective cohort study among patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

Leukocyte extracellular vesicle concentration is inversely associated with liver fibrosis severity in NAFLD.

The enhanced liver fibrosis (LFS) score and the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are algorithmic-derived scores for diagnosing severe (F3/F4) liver fibrosis. In a pilot, substudy of the Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy (WELCOME) trial, we tested whether measurements of plasma platelet-, endothelial-, and leukocyte-derived extracellular vesicles (EVs) counts are (a) associated with, and predict, F3/F4 fibrosis and (b) able to improve risk prediction of F3/F4 fibrosis in NAFLD, building upon LFS or NFS algorithms. Twenty-six individuals with NAFLD had liver fibrosis severity determined by Kleiner scoring after liver biopsy. Plasma samples stained with CD41a, CD42b, CD31, CD105, CD14, CD16, and CD284 antibodies were analyzed using flow cytometry to measure platelet-, endothelial-, and leukocyte-derived EVs counts. The independence of associations between EVs and F3/F4 fibrosis were tested using logistic regression. Receiver operator characteristic (ROC) curves were used to evaluate F3/F4 fibrosis prediction models. LFS was more strongly associated with F3/F4 fibrosis than NFS (χ2=15.403, P<0.0001, and χ2=6.300, P=0.012, respectively). The association between LFS and F3/F4 fibrosis was further improved by addition of CD14+ EVs (χ2=20.847,P=0.016 vs. χ2=12.803,P=0.015, respectively) or CD16+ EVs (χ2=22.205,P=0.009 vs. χ2=17.559,P=0.001, respectively), and the area under the ROC for LFS (AUC=0.915, se=0.055, P=0.001) was increased by the addition of CD14+ or CD16+ EVs (AUC=0.948, se=0.042, and P<0.001 and AUC=0.967, se=0.055, P<0.001, respectively) as predictor variables. In this small preliminary study, CD14+ and CD16+ EV counts show potential to predict liver fibrosis severity with either marker improving the ability of the LFS to identify F3/F4 fibrosis in this small preliminary cohort study.

Race affects SVR12 in a large and ethnically diverse hepatitis C-infected patient population following treatment with direct-acting antivirals: Analysis of a single-center Department of Veterans Affairs cohort.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct‐acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African‐Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non‐CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA‐treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single‐center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African‐American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non‐SVR. African‐Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5‐4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26‐0.68) was also a significant predictor of non‐SVR. In a single‐center VA population on DAAs, African‐Americans were less likely than White people to reach SVR12 when adjusting for covariates.

Diagnosis of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Non-invasive tests are enough.

Non-alcoholic fatty liver disease is a major cause of liver disease worldwide and the most common liver disorder in Western countries, affecting around 25% of the general population. Fibrosis is the major long-term histological prognostic criteria of this disease. Liver biopsy cannot be realistically performed in such a huge population and, moreover, has well-known limitations (invasiveness, rare but potentially life-threatening complications and sampling variability). Over the past decade, there has been a growing interest in alternative novel strategies for the non-invasive evaluation of fibrosis. These tests rely on two different but complementary approaches: either measuring the levels of serum biomarkers, or liver stiffness, using ultrasound-based elastography techniques. In non-alcoholic fatty liver disease patients, transient elastography, FIB-4 and the non-alcoholic fatty liver disease fibrosis score are the best validated tests, with summary area under the ROC curve values for diagnosing severe fibrosis-cirrhosis of 0.88, 0.84 and 0.84 respectively. They can also identify the subgroup of non-alcoholic fatty liver disease patients at high risk of developing liver-related complications and death. As a result, non-invasive tests are now widely used in routine clinical practice and included in national and international guidelines. The next step is the use of non-invasive tests as first-line tools for screening non-alcoholic fatty liver disease in the general population to identify patients who should be referred to specialized centres.

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes.

To evaluate the application of the recently proposed recommendations by the European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease in people with Type 2 diabetes. A total of 179 people with Type 2 diabetes were included in this study. Liver fat content (assessed using proton magnetic resonance spectroscopy), fatty liver index score, non-alcoholic fatty liver disease fibrosis score, and SteatoTest and FibroTest scores were determined. According to proton magnetic resonance spectroscopy, 68.7% of participants had steatosis (liver fat content >5.5%). The application of the guidelines using several combinations (fatty liver index + non-alcoholic fatty liver disease fibrosis scores, Steatotest + FibroTest scores, proton magnetic resonance spectroscopy + non-alcoholic fatty liver disease fibrosis score, proton magnetic resonance spectroscopy + FibroTest) resulted in a referral to a liver clinic for 33.5-84.9% people with Type 2 diabetes. The application of these new algorithms for the diagnosis, and follow-up of non-alcoholic fatty liver disease would lead to an excessive number of people with Type 2 diabetes being referred to a liver clinic. We suggest that new clinical and/or biological biomarkers of steatosis and fibrosis be specifically validated in people with Type 2 diabetes.

Vegetarian diet, food substitution, and nonalcoholic fatty liver.

Objectives:Vegetarian diets have been shown to improve insulin resistance and reduce body weight, but the effects on nonalcoholic fatty liver require further confirmation. We aim to investigate the association between vegetarian diets, major food groups, and nonalcoholic fatty liver, and to compare the degree of liver fibrosis between vegetarians and nonvegetarians in those with fatty liver.Materials and Methods:We analyzed cross-sectional data from the Tzu Chi Health Study which included 2127 nonvegetarians and 1273 vegetarians who did not smoke or habitually drink alcohol and had no hepatitis B or hepatitis C. Fatty liver and liver fibrosis were determined using ultrasonography and the nonalcoholic fatty liver disease fibrosis score, respectively. Diet was assessed through a validated food frequency questionnaire.Results:Vegetarian diets were associated with lower odds of fatty liver (odds ratio = 0.79, 95% confidence interval: 0.68–0.91) after adjusting for age, gender, education, history of smoking and alcohol drinking. Adjustment for body mass index (BMI) attenuated the protective association. Vegetarians had less severe fibrosis than nonvegetarians. Replacing a serving of soy with a serving of meat or fish was associated with 12%–13% increased risk, and replacing a serving of whole grains with a serving of refined grains, fruits, and fruit juice was associated with 3%–12% increased the risk of fatty liver.Conclusion:Vegetarian diets, replacing meat and fish with soy, and replacing refined carbohydrates with whole grains, may be inversely associated with nonalcoholic fatty liver related to BMI.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction.

AimsHeart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non‐alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid.Methods and resultsWe performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first–fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B‐type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B‐type natriuretic peptide, and NFS (P < 0.001 each). In the follow‐up period (mean 1107 days), 93 deaths occurred. All‐cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all‐cause mortality in the HFpEF patients.ConclusionsNFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all‐cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients.

Degree of Estimated Fibrosis in Asymptomatic Subjects With Non-Alcoholic Fatty Liver Disease Correlates With Higher Cardiovascular Risk

Introduction: Our aim is to assess the estimated 10-year atherosclerotic cardiovascular (ASCVD) risk scores in patients with NAFLD according to the degree of estimated fibrosis by Non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Methods: Cross-sectional observational study from a single center in Mexico conducted as a case control analysis in asymptomatic outpatients. NAFLD cases were defined by a positive ultrasound. Estimated 10-year ASCVD risk was calculated with the 2013 American College of Cardiology and the American Heart Association (2013 ACC/AHA) risk equation, Framingham risk score for coronary heart disease (FRS-CHD). High ASCVD risk was defined according to standardized cutoff points: for 2013 ACC/AHA (>= 7.5%) and Framingham (> =20%). NFS was stratified according to the following cut-off points into three groups with progressive degree of fibrosis (<-1.455: F0-F2, >=-1.455-≤ 0.675: indeterminate score, >0.675: F3-F4 fibrosis). Results: We included data from 141 patients with NAFLD by ultrasound and 354 healthy controls. 62% were males, BMI of 25.9 (SD ± 3.9) Kg/m2, 45 (SD ± 11.5) years old. We previously excluded patients with significant alcohol consumption (defined by >30 gr/day in men, >20 g/day in women). NAFLD vs. controls patients had higher mean cardiovascular risk assesed by FRS and 2013 ACC/AHA with 7.1 vs 4.1%(p=0.05) and 5.7 vs 4.4% (p=0.05), respectively, additionally a selected cutoff point for FRS (=>10%) showed a strong association with NAFLD [OR = 5.05 (95% CI 2.1 - 11.9, p < 0.01)]. Global 10-year ASCVD risk was in the case group: for ACC/AHA 5.8% (CI: 95% 4.6-6.9), FRS-CHD 7.2% (CI: 95% 6.1-8.2). Higher degree of fibrosis by NFS correlated with higher FRS risk with a median of 3.5 (RIQ 1.3-7.5), 3.9 (RIQ 2.0-5.7), 8.7 (RIQ 5.3-13.1), for NFS cut-off points F0-F2, indeterminate score, F3-F4 fibrosis, respectively (p < 0.01). High cardiovascular risk estimated for FRS was strongly associated with F3-F4 fibrosis [OR = 9.8 (95% CI 1.17 - 81, p=0.011)]. Total NFS and FRS scores showed correlation with a spearman's Rho of 0.49, (p < 0.001).Figure: Comparison between estimated 10-year risk by Framingham score and NAFLD fibrosis score in patients with ultrasonographic fatty liver disease (n=141).Conclusion: NAFLD patients have higher ASCVD risk than healthy subjects. Higher estimated fibrosis by NAFLD score correlated with higher 10-year ASCVD risk in asymptomatic patients with ultrasonographic fatty liver disease. Presence of higher estimated NFS in fatty liver disease should prompt cardiovascular risk assessment and intervention.

P19-2 - Liver Fibrosis Predicts Mortality in Heart Failure Patients With Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects including stiffness of multiple organs. According to recent research, liver stiffness assessed by transient elastography predicts adverse prognosis in heart failure patients. Liver fibrosis can be assessed by nonalcoholic fatty liver disease (NAFLD) fibrosis score (−1.675 + 0.037 × age [years] + 0.094 × body mass index + 1.13 × diabetes mellitus [if presence, given 1] + 0.95 × AST [IU/L]/ALT [IU/L] − 0.013 × platelet count [10−9/L] − 0.66 × albumin [g/dL]) in patients with NAFLD. We aimed to investigate the impact of NAFLD fibrosis score (NFS) on prognosis of HFpEF patients. Methods and Results: We analyzed consecutive 492 patients with HFpEF who admitted to our hospital without chronic liver disease. These patients were divided into 4 groups based on the NFS: 1st (NFS < −1.12, n = 123), 2nd (−1.13 < NFS < 0.19, n = 123), 3rd (0.20 < NFS < 1.55, n = 123) and 4th (1.56 < NFS, n = 123) quartiles. In the follow-up period (mean 1107 days), 93 deaths (33 cardiac and 60 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1st to 2nd, 3rd and 4th groups (8.1%, 12.2%, 23.6% and 31.7%, log rank P < .001). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, NFS was an independent predictor of all-cause mortality in HFpEF patients (hazard ratio 1.98, 95% confidence interval 1.43–3.19, P < .001). Conclusion: NAFLD fibrosis score, a marker of liver fibrosis, can identify high risk patients with HFpEF.

Non-alcoholic fatty liver and advanced fibrosis in the elderly: Results from a community-based Polish survey.

Development of non-alcoholic fatty liver (NAFL) is dependent on metabolic factors occurring at an increased frequency with advancing age. Until now, few studies have explored the prevalence of NAFL in aged populations. Our study aimed to determine the prevalence of NAFL and advanced fibrosis in the elderly population participating in a national survey of a community-based elderly cohort. A total of 3003 participants (mean age 79.6years, 46.8% male) were enrolled in the study, after applying the following exclusion criteria: individuals younger than 65years old (n=829) and those with positive serological biomarkers of HBV or HCV infection (n=391), chronic alcohol ingestion (n=727) or incomplete data records (n=745). Based on the fatty liver index (FLI), the participants were classified into three categories: FLI<30 (no NAFL), 30≤FLI<60 (borderline) and FLI≥60 (NAFL). According to the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), the participants were divided into three advanced fibrosis risk categories: NFS<-1.455 (low risk), -1.455≤NFS≤0.676 (intermediate risk) and NFS>0.676 (high risk). The prevalence of NAFL in the general population was 37.2%; the prevalence reached 51.4% in participants 65-70years of age and decreased with advancing age (P<.0001). The prevalence of advanced fibrosis was 7.79% (14.8% in the NAFL population) and increased with advancing age (P<.005). The prevalence of NAFL and metabolically driven advanced fibrosis are relatively common in the elderly population, and these hepatic conditions run in adverse directions with advancing age.

External validation of the non-alcoholic fatty liver disease fibrosis score for assessing advanced fibrosis in Korean patients.

The degree of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) is a critical predictive factor for patient prognosis. This study was intended to perform external validation of the various fibrosis prediction models for assessing advanced fibrosis in Korean NAFLD patients. A retrospective study of 412 patients with NAFLD confirmed by liver biopsy in hospitals affiliated with the Koran NAFLD study group was conducted and the predictive ability of existing liver fibrosis prediction models including NAFLD fibrosis score (NFS), BARD, and fibrosis-4 were compared. Among 412 samples, 328 liver slides were suitable for evaluation. Advanced fibrosis was present in 60 (18.3%) of the patient samples. Univariate analysis found that the group with advanced fibrosis showed low alanine aminotransferase values and high aspartate aminotransferase/alanine aminotransferase ratios as well as a high incidence of diabetes. However, multivariate analysis showed that only the presence of diabetes and triglycerides was independent risk factors. The receiver operating characteristic was 0.64 in NFS, 0.58 in fibrosis-4, and 0.594 in the BARD model. The NFS was found to be the best at predicting advanced fibrosis among the three prediction models. The negative predictive value which predicts advanced fibrosis using the low cutoff (<-1.455) was high (86.6%). However, the positive predictive value which predicts advanced fibrosis using the high cutoff (>0.676) was 50.0% when we applied the NFS. Negative predictive value using the low cutoff value was high, but positive predictive value using the high cutoff value was low in a Korean NAFLD cohort using NFS.

Non-alcoholic fatty liver disease fibrosis score predicts hematological toxicity of chemotherapy including irinotecan for colorectal cancer.

Liver dysfunction that may affect drug metabolism is a major concern in patients treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is crucial for predicting the adverse events of chemotherapy. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring system constructed from routine clinical and laboratory variables. The aim of this study was to evaluate whether NFS was useful for predicting the adverse events of chemotherapy including irinotecan (CPT-11) for colorectal cancer. Between January, 2007 and May, 2013, a total of 87 patients with unresectable/recurrent colorectal cancer who received first-line chemotherapy including CPT-11 were reviewed. Demographic variables, including pretreatment NFS, were retrospectively collected from medical records. The primary outcome was the association between pretreatment NFS and adverse events, such as hematological and non-hematological toxicity, of chemotherapy including CPT-11. The median pretreatment NFS was 1.302 (range, 5.158-2.620). Pretreatment NFS was an independent risk factor for hematological toxicity in a multivariate analysis (coefficient=0.932, 95% CI: 0.083-1.781; P=0.031). Receiver operating characteristic curve analysis identified 0.347 as the optimal cut-off value associated with hematological toxicity. Using this cut-off, high NFS was found to be a significant risk factor for hematological toxicity (coefficient=2.019, 95% CI: 0.239-3.798, P=0.026), but not for non-hematological toxicity (P=0.546). Therefore, based on these results, NFS appears to be a significant predictor of hematological adverse events in chemotherapy including CPT-11 for colorectal cancer and it is a non-invasive, useful tool that may be used for determining regimens or doses of chemotherapy including CPT-11.

Abstract 13894: Prediction of Mode of Death by Model of End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System in Patients Admitted for Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction; a Comparison With Nonalcoholic Fatty Liver Disease Fibrosis Score

Backgrounds: Cardiohepatic interactions have been a focus of attention among heart failure. A model of end-stage liver disease excluding INR (MELD-XI), a robust scoring system of liver dysfunction, has been shown to provide prognostic information in heart failure patients (pts). Furthermore, it was reported that nonalcoholic fatty liver disease (NAFLD) is a risk factor for cardiovascular disease. There is a difference in mode of death (cardiac vs non-cardiac death) between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). We sought to investigate the prognostic significance of MELD-XI and NAFLD in the prediction of mode of death in pts admitted for acute decompensated heart failure (ADHF), relating to HFpEF and HFrEF. Methods and Results: We studied 303 consecutive ADHF pts (HFrEF[LVEF&lt;50%]; n=163, HFpEF[LVEF≥50%];n=140). MELD-XI score was calculated by the formula: 5.11х ln(bilirubin)+11.79х ln(creatinine)+9.44. NAFLD fibrosis score (NFS) was obtained by the formula: -1.675 + 0.037 х age + 0.094 х BMI + 1.13 х hyperglycemia or diabetes (yes = 1, no = 0) + 0.99 х AST/ALT - 0.013 х platelet ( х 10 9 /L) - 0.66 х albumin. During a follow-up period of 5.1±4.3 yrs, 65 pts had cardiac death and 56 pts had non-cardiac death. At multivariate Cox analysis, MELD-XI score, but not NFS, was significantly associated with cardiac death independently of prior heart failure hospitalization, BMI, systolic blood pressure and serum sodium level, while neither MELD-XI score nor NFS showed the association with non-cardiac death. MELD-XI of 13 was a fair discriminator for cardiac death (AUC 0.737[0.670-0.805]). In both groups with HFrEF and HFpEF, pts with higher MELD-XI score had a significantly higher risk of cardiac death than those with lower MELD-XI score. Conclusion: A MELD-XI scoring system might predict cardiac death but not non-cardiac death in ADHF pts, regardless of HFrEF or HFpEF, although NAFLD fibrosis score did not.

Abstract 11590: Liver Fibrosis Score Predicts Mortality in Heart Failure Patients With Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects including stiffness of multiple organs. It has been recently reported that liver stiffness assessed by transient elastography predicts adverse prognosis in heart failure patients. Liver fibrosis is assessed by nonalcoholic fatty liver disease (NAFLD) fibrosis score (based on age, body mass index, aspartate aminotransferase [AST] to alanine aminotransferase [ALT] ratio, platelet counts and albumin) in patients with NAFLD. We aimed to investigate the impact of NAFLD fibrosis score on prognosis of HFpEF patients. Methods and Results: We analyzed consecutive 510 patients with HFpEF who admitted to our hospital. Out of these 510 HFpEF patients, patients with hepatitis and chronic liver disease were excluded, and 492 patients were finally analyzed. Liver fibrosis was estimated by NAFLD fibrosis score (= - 1.675 + 0.037 х age [years] + 0.094 х body mass index + 1.13 х diabetes mellitus [if presence, given 1] + 0.95 х AST [IU/L]/ ALT [IU/L] - 0.013 х platelet count [10- 9 /L] - 0.66 х albumin [mg/L]). These patients were divided into 4 groups based on the NAFLD fibrosis score: 1 st (NAFLD fibrosis score &lt; -1.13, n = 123), 2 nd (-1.13 ≤ NAFLD fibrosis score &lt; 0.20, n = 123), 3 rd (0.20 ≤ NAFLD fibrosis score &lt;1.56, n = 123) and 4 th (1.56 ≤ NAFLD fibrosis score, n = 123) quartiles. In the follow-up period (mean 1107 days), 93 deaths (33 cardiac deaths and 60 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1 st to 2 nd , 3 rd and 4 th groups (8.1%, 12.2%, 23.6% and 31.7%, P &lt;0.001). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, NAFLD fibrosis score was an independent predictor of all-cause mortality in HFpEF patients (hazard ratio 1.98, 95% confidence interval 1.43-3.19, P &lt; 0.001). Conclusion: NAFLD fibrosis score, a marker of liver fibrosis, can identify high risk patients with HFpEF.

The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer.

Background:The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC.Methods:Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses.Results:A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4–94.7 vs NL 96.0%, 95% CI 94.3–97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23–7.21; P=0.02).Conclusion:HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC.

Non-alcoholic fatty liver disease fibrosis score and preclinical vascular damage in morbidly obese patients

BackgroundNon-alcoholic fatty liver disease (NAFLD) is strongly related with enhanced morbidity and mortality from cardiovascular disease. In obese patients with both NAFLD and features of the metabolic syndrome, the cardiovascular risk is further increased. AimThe aim of this study is to investigate the relationship between severity of liver fibrosis evaluated by NAFLD fibrosis score (NAFLD-FS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), other obesity-related markers and preclinical atherosclerosis in morbidly obese patients with previously diagnosed NAFLD. MethodsLaboratory parameters, visceral fat area (VFA), flow-mediated dilatation (FMD), intima-media thickness (IMT), HOMA-IR and NAFLD-FS were determined in 196 morbidly obese patients. ResultsPatients with higher NAFLD-FS or HOMA-IR show higher left max-IMT and lower FMD (p<0.001). VFA and NAFLD-FS, but not HOMA-IR, were independent predictors of reduced FMD (respectively β −0.268, p=0.001 and β −0.165, p=0.039, p of the model<0.001) and increased left max-IMT (respectively β 0.165, p=0.031 and β 0.301, p<0.001, p of the model<0.001). ConclusionsIn morbidly obese patients, NAFLD-FS correlates with markers of early vascular damage. NAFLD-FS, easier to obtain than VFA, seems to be a better score than HOMA-IR to categorize such subjects who are potentially at risk of future cardiovascular events.