Fatty Liver Disease Fibrosis Score Research Articles

Liver fibrosis scores and coronary atherosclerosis: novel findings in patients with stable coronary artery disease

Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up. A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively. During a median follow-up of 7years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012]. The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs. None.

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score>0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.

Factors Associated with Prognosis of Non-Alcoholic Fatty Liver Disease

Background: At the junction between obesity, metabolic syndrome and liver failure, lies Non-alcoholic fatty liver disease. Recent studies elaborated on role of metformin in patients with non-alcoholic fatty liver disease. This observation has not been studied at a global scale, neither it was investigated in different ethnical groups.&#x0D; Objectives: We aim at determining the risk factors associated with prognosis of non-alcoholic fatty liver disease among a cohort of patients in Southern West Bank, Palestine.&#x0D; Methods: A retrospective cohort study involving 300 NAFLD patients who visited the internal medicine department at Hebron Governmental Hospital from October 2017 till September 2018. Two hundred and three patients diagnosed with non-alcoholic fatty liver disease, were included in this study. Lab test results within the past 6 months, comorbidity and medication history were collected from patients` profiles. Data was analyzed using SPSS V20. Liver Fibrosis score was determined by using non-alcoholic fatty liver disease fibrosis score calculator.&#x0D; Results: Two hundred and three non-alcoholic fatty liver disease patients (58.6% females), 54.78 (±12.27) years old were included in the study. Almost 65.5% of these patients have BMI &gt;30 Kg/m2. It was found that, 62.25% of the 58 diabetic patients in this study had liver fibrosis score &gt; 0.676 comparing to non-alcoholic fatty liver disease patients who are non-diabetic. There was a significant relationship between diabetes and fibrosis score, α=0.000. There was also a significant relationship between hyperlipidemia and fibrosis score of non-alcoholic fatty liver disease patients, α=0.023. We found a significant relationship between fibrosis score and hypertension, α=0.000. In the same context, there was a significant relationship between NAFLD patients who were on statin therapy and those who were not using statin therapy, α= 0.015. Metformin was not associated with significant relationship between users and non-users non-alcoholic fatty liver disease subjects.&#x0D; Conclusion: Diabetes mellitus, hypertension, hyperlipidemia and statin use were associated with NAFLD prognosis.

The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan.

PurposeTo examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver.Patients and MethodsThis cross-sectional study included 1817 participants aged ≥65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and >0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤2.67 and >2.67, respectively).ResultsCompared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50–3.93), 2.35 (1.25–4.41), and 6.11 (3.90–9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83–2.18), 2.37 (1.36–4.13), and 1.38 (0.82–2.31) in the MUNO, MHO, and MUO groups, respectively.ConclusionBoth metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.

Efficacy and Safety of Luseogliflozin in Patients with Type2 Diabetes Complicated by Hepatic Dysfunction: A Single-Site, Single-Arm, Open-Label, Exploratory Trial.

IntroductionImprovements in glycemic control and hepatic function are clinically important goals in the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by hepatic dysfunction. The favorable effects of the sodium–glucose co-transporter inhibitor luseogliflozin on hepatic dysfunction were anticipated for humans. Nevertheless, few clinical studies have confirmed its real-world efficacy on hepatic dysfunction. This trial assessed the efficacy and safety of luseogliflozin in patients with T2DM complicated by hepatic dysfunction.MethodsThis prospective, single-site, single-arm, open-label, exploratory trial included 55 subjects with T2DM complicated by hepatic dysfunction. Subjects were administered luseogliflozin and observed for 52 weeks. The primary endpoints were the change in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), and hemoglobin A1c (HbA1c) from baseline to week 52. The secondary endpoints included body weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), homeostatic model assessment beta (HOMA-β), homeostatic model assessment of insulin resistance (HOMA-IR), ferritin, Mac-2 binding protein (M2-BP), fatty liver index (FLI), fibrosis-4 (FIB-4) index, type IV collagen 7S domain, nonalcoholic fatty liver disease (NAFLD) fibrosis score, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6).ResultsAST, ALT, γ-GTP, and HbA1c significantly decreased from baseline to week 52. Body weight, BMI, waist circumference, and FPG also significantly decreased. HOMA-IR significantly decreased but HOMA-β was unchanged. FLI, ferritin, M2-BP, and NAFLD fibrosis scores significantly decreased whereas the FIB-4 index and type IV collagen 7S domain did not significantly change. The hs-CRP and IL-6 levels did not significantly change.ConclusionLuseogliflozin administration in patients with T2DM complicated by hepatic dysfunction was well tolerated, did not worsen the hepatic condition, and might even be beneficial to improve hepatic function, reduce liver fat, and attenuate liver injury and fibrosis.Trial RegistrationThis study was registered under the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (No. UMIN000025808) and the Japan Registry of Clinical Trials (jRCT) (No. jRCTs021180017).

Association of liver fibrosis risk scores with clinical outcomes in patients with heart failure with preserved ejection fraction: findings from TOPCAT.

AimsNon‐alcoholic fatty liver disease leads to progressive liver fibrosis and appears to be a frequent co‐morbid disease in heart failure with preserved ejection fraction (HFpEF). It is well known that liver fibrosis severity predicts future liver‐related morbidity and mortality, but its impact on outcomes in patients with HFpEF remains unknown. This analysis aimed to describe the prevalence of liver fibrosis, as assessed using surrogate biomarkers, in patients with HFpEF and the association of such biomarkers in predicting clinical outcomes in these patients.Methods and resultsPatients with HFpEF from TOPCAT Americas were included in the analysis. The non‐alcoholic fatty liver disease fibrosis score (NFS) and fibrosis‐4 (FIB‐4) scores were calculated using a combination of clinical characteristics and laboratory parameters. Risk of advanced fibrosis was classified as low, intermediate, and high. For the 1423 with sufficient data, we used Cox regression analysis to test the association between the risk of fibrosis severity and the combined primary endpoint of all cardiovascular death, aborted cardiac arrest, and hospitalization for heart failure. Advanced fibrosis, as determined by high fibrosis scores, was present in 37.57% by the NFS and 8.02% by the FIB‐4. Higher risk of advanced hepatic fibrosis was associated with older age. In unadjusted models, the risk of advanced fibrosis was associated with the primary cardiovascular outcome [NFS high vs. low, hazard ratio (HR) 1.709 (95% confidence interval, CI 1.238–2.358, P = 0.0011) and FIB‐4 high vs. low, HR 1.561 (95% CI 1.139–2.140, P = 0.0056)]. After multivariable adjustment, this association was diminished [NFS high vs. low, HR 1.349 (95% CI 0.938–1.939, P = 0.1064) and FIB‐4 high vs. low, HR 1.415 (95% CI 0.995–2.010, P = 0.0531)].ConclusionsOur study suggests that advanced liver fibrosis, as estimated by fibrosis risk scores, may not be uncommon in patients with HFpEF, and there appears to be a limited independent association between liver fibrosis risk scores and clinical outcomes related to heart failure events.

Importance of non-invasive liver fibrosis scores for mortality and complications development in individuals with type 2 diabetes.

To evaluate the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 score (FIB4) as predictors of complications development and mortality in a cohort of type 2 diabetes. 554 type 2 diabetic subjects had NFS and FIB4 calculated at baseline. Multivariate Cox and Poisson analyses evaluated the associations between fibrosis scores and the occurrence of microvascular and cardiovascular complications, and all-cause mortality. According to recommended cut-offs of NFS, 12.8% had advanced fibrosis and 45.9% had absence of advanced fibrosis and of FIB4, 3.8% and 86.1%, respectively. During a median follow-up of 11 years, 217subjects died, 172 had cardiovascular events (CVEs), 184 had renal events, and 139 had retinopathy and 185 neuropathy events. As continuous variables, both scores predicted all-cause mortality: NFS, HR: 1.30 (p = 0.032) and FIB4, HR: 1.24 (p = 0.021); an increased NFS implied in a significant 90% excess risk of mortality, whereas a higher FIB4 in a borderline 69% higher risk. The scores were mainly predictors of mortality in women and for non-cardiovascular deaths. The NFS was a predictor of renal events, mainly for renal function deterioration. The NFS and FIB4 predicted all-cause mortality, particularly in women and for non-cardiovascular causes. The NFS predicted adverse renal outcomes. These liver fibrosis scores may improve stratification risk in individuals with diabetes and NAFLD.

Liver Fibrosis Scoring Systems as Novel Tools for Predicting Cardiovascular Outcomes in Patients Following Elective Percutaneous Coronary Intervention.

BackgroundPrevious studies have suggested a strong association of liver fibrosis scores (LFSs) with cardiovascular outcomes in patients with different cardiovascular diseases. Nonetheless, it is basically blank regarding the prognostic significance of LFSs in patients following percutaneous coronary intervention (PCI). This study sought to examine the potential role of LFSs in predicting long‐term outcomes in a large cohort of patients with stable coronary artery disease after elective PCI.Methods and ResultsIn this multicenter, prospective study, we consecutively enrolled 4003 patients with stable coronary artery disease undergoing PCI. Eight currently available noninvasive LFSs were assessed for each subject. All patients were followed up for the occurrence of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average follow‐up of 5.0±1.6 years, 315 (7.87%) major cardiovascular events were recorded. Subjects who developed cardiovascular events were more likely to have intermediate or high LFSs, including nonalcoholic fatty liver disease fibrosis score; fibrosis‐4 score; body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score (BARD); and aspartate aminotransferase/alanine aminotransferase ratio. Furthermore, compared with subjects with low scores, those with intermediate plus high score levels had significantly increased risk of cardiovascular events (adjusted hazard ratios ranging 1.57–1.92). Moreover, the addition of non‐alcoholic fatty liver disease fibrosis score; fibrosis‐4 score; or body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score into a model with established cardiovascular risk factors significantly improved the prediction ability.ConclusionsHigh LFSs levels might be useful for predicting adverse prognosis in patients with stable coronary artery disease following PCI, suggesting the possibility of the application of LFSs in the risk stratification before elective PCI.

SOMAscan Proteomics Identifies Serum Biomarkers Associated With Liver Fibrosis in Patients With NASH.

Nonalcoholic steatohepatitis (NASH) is a major cause of liver‐related morbidity and mortality worldwide. Liver fibrosis stage, a key component of NASH, has been linked to the risk of mortality and liver‐related clinical outcomes. Currently there are no validated noninvasive diagnostics that can differentiate between fibrosis stages in patients with NASH; many existing tests do not reflect underlying disease pathophysiology. Noninvasive biomarkers are needed to identify patients at high‐risk of NASH with advanced fibrosis. This was a retrospective study of patients with histologically proven NASH with fibrosis stages 0‐4. The SOMAscan proteomics platform was used to quantify 1,305 serum proteins in a discovery cohort (n = 113). In patients with advanced (stages 3‐4) versus early fibrosis (stages 0‐2), 97 proteins with diverse biological functions were differentially expressed. Next, fibrosis‐stage classification models were explored using a machine learning–based approach to prioritize the biomarkers for further evaluation. A four‐protein model differentiated patients with stage 0‐1 versus stage 2‐4 fibrosis (area under the receiver operating characteristic curve [AUROC] = 0.74), while a 12‐protein classifier differentiated advanced versus early fibrosis (AUROC = 0.83). Subsequently, the model’s performance was validated in two independent cohorts (n = 71 and n = 32) with similar results (AUROC = 0.74‐0.78). Our advanced fibrosis model performed similarly to or better than Fibrosis‐4 index, aspartate aminotransferase–to‐platelet ratio index, and nonalcoholic fatty liver disease (NAFLD) fibrosis score–based models for all three cohorts. Conclusion: A SOMAscan proteomics‐based exploratory classifier for advanced fibrosis, consisting of biomarkers that reflect the complexity of NASH pathophysiology, demonstrated similar performance in independent validation cohorts and performed similarly or better than Fibrosis‐4 index, aspartate aminotransferase–to‐platelet ratio index, and NAFLD fibrosis score. Further studies are warranted to evaluate the clinical utility of these biomarker panels in patients with NAFLD.

Association between the severity of liver fibrosis and cardiovascular outcomes in patients with type 2 diabetes.

Cardiovascular disease (CVD) is the principal cause of death in patients with type 2 diabetes (T2D). In this study, we assessed whether liver fibrosis predicted the risk of CVD in patients with T2D. A total of 1481 patients who had commenced oral antidiabetic drugs to treat newly diagnosed T2D between 2006 and 2010 were recruited. The fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), and BARD score were used to assess fibrotic burden at the time of T2D diagnosis. During the follow-up period (median 88.1 [interquartile range 36.6-113.6] months), 242 (16.3%) patients developed CVD. CVD occurred frequently in older patients and was associated with hypertension; metabolic syndrome; obesity; smoking; administration of statin, which is an antihyperlipidemic drug; lower platelet counts; lower alanine aminotransferase, total cholesterol, and HbA1c levels; higher C-peptide and homeostatic model assessment of insulin resistance levels; and higher FIB-4, NFS, and BARD score (all P<0.05). FIB-4 (hazard ratio [HR]=1.163), NFS (HR=1.322), BARD score (HR=1.564), metabolic syndrome (HR=1.556), smoking (HR=2.829), and statin use (HR=0.603) independently predicted the risk of CVD (all P<0.05). The cumulative incidence of CVD was significantly different among groups stratified by liver fibrotic burden (all P<0.05, log-rank test). Competing risk analysis showed a significant association between the severity of liver fibrosis and CVD development (all P<0.001, Gray's test). The severity of liver fibrosis independently predicted CVD in patients with T2D. Thus, assessment of liver fibrosis might allow physicians to optimize the timing of appropriate cardiovascular interventions in such patients.

Impact of liver fibrosis score on prognosis in patients with previous myocardial infarction: A prospective cohort study.

Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. We aimed to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score were used. The CVOs covered major adverse cardiac event (MACEs), cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). During a mean follow-up of 47.4±24.8months, 431 (11.6%) MACEs occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CIs) of the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.75 (1.32-2.33), 2.37 (1.70-3.33), 2.44 (1.61-3.73), 1.58 (1.16-2.14) and 1.27 (1.03-1.57) respectively. These LFSs were also independent predictors of cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. The present study firstly demonstrated that LFS could be used as a risk stratification tool for predicting CVOs in patients with previous MI, which should be evaluated further.

Association of the Non-Alcoholic Fatty Liver Disease Fibrosis Score with subclinical myocardial remodeling in patients with type2 diabetes: A cross-sectional study in China.

Aims/IntroductionNon‐alcoholic fatty liver disease, especially with liver fibrosis, is associated with cardiovascular diseases. The Non‐Alcoholic Fatty Liver Disease Fibrosis Score (NFS), a non‐invasive marker of advanced fibrosis, was found to be associated with cardiovascular diseases in different populations. The aim of the present study was to determine whether the NFS is associated with subclinical myocardial remodeling in type 2 diabetes patients.Materials and MethodsA cross‐sectional study was carried out in type 2 diabetes patients. The NFS derived from available parameters was calculated, and the participants were divided according to the quartiles of the NFS and grades of the NFS (low, intermediate and high). Fibrosis‐4 and Aspartate Aminotransferase to Platelet Ratio Index, another two liver fibrosis scores, were also calculated. Subclinical myocardial remodeling was examined by echocardiography, and its associations with NFS, Fibrosis‐4 and Aspartate Aminotransferase to Platelet Ratio Index were analyzed.ResultsA total of 1,878 type 2 diabetes patients were enrolled in the present study. The NFS was independently associated with sex, age, body mass index, low‐density lipoprotein cholesterol and glycated hemoglobin in type 2 diabetes patients. Parameters of subclinical myocardial remodeling including left atrial dimension, interventricular septum thickness, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, left ventricular posterior wall thickness (LVPWT) and left ventricular mass index were all gradually increased with the increment of the NFS. Linear regression analysis further showed that the NFS was positively associated with left atrial dimension, interventricular septum thickness, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, LVPWT and left ventricular mass index after adjustment for the confounding factors. Similarly, Fibrosis‐4 was associated with left atrial dimension, interventricular septum thickness, LVPWT and left ventricular mass index. In contrast, the Aspartate Aminotransferase to Platelet Ratio Index was only associated with LVPWT.ConclusionsNon‐invasive liver fibrosis scores, especially the NFS, are independently associated with subclinical myocardial remodeling in type 2 diabetes patients.

Association of PNPLA3 I148M with Liver Disease Biomarkers in Latinos

Introduction: Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help to estimate liver damage, including AST-to-ALT ratio, AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. The aims of the present study were to (1) perform an association analysis of the patatin-like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) variant with ALT, AST, and various liver fibrosis indices, and (2) determine whether there are gender-related differences in these associations. Methods: We obtained demographic, anthropometric, and metabolic phenotypes from Latino adult participants (n = 503, 64% female, 36.4 ± 0.5 years) from the Arizona Insulin Resistance (AIR) registry. SNP genotyping of I148M was performed using the TaqMan allelic discrimination assay. We used linear regression for the association analyses of the genotypes with ALT, AST, and the various liver fibrosis indices. We included genotype, age, body mass index, and alcohol status in the linear regression model. Results: The variant I148M was in Hardy-Weinberg equilibrium, with genotype distribution: non-risk CC 118, heterozygous CG 246, and risk GG 139. The G allele was significantly associated with increased ALT and AST levels (p = 7.8 × 10^–7 and p = 9.7 × 10^–6, respectively). Moreover, we showed that the G allele was significantly associated with higher APRI (p = 3.7 × 10^–7) and FIB-4 score (p = 4.1 × 10^–3). When we analyzed the data by gender, we observed similar significant trends for ALT, AST, and APRI (all, p < 0.01). In females, the G allele was significantly associated with increased FIB-4 score (p = 6.9 × 10^–3), which was not observed in the males (p > 0.05). There was no association of the I148M variant with AST/ALT ratio nor NAFLD risk score, whether analyzed in all adults or by gender. Discussion/Conclusion: Our findings provide additional evidence of an association of PNPLA3 I148M with several liver disease biomarkers in male and female Latinos residing in the Southwest of the United States.

The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis

Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 ± 14.2 kPa in F4 disease and 14.6 ± 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 ± 1.2 in F4 disease and 10.3 ± 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, ≥10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, ≥1.80; Fibrotest score, ≥0.54; liver stiffness, ≥23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).

An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study.

So far, no study has investigated the association between subclinical hepatic fibrosis and sepsis, especially in terms of prognosis. The purpose of our study was to explore the association of liver fibrosis indexes with the outcomes of septic patients without overt chronic liver disease. We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care III (version 1.4) database. External validation was obtained from the First Affiliated Hospital of Wenzhou Medical University, China. We calculated the Aspartate Aminotransferase-to-Platelet Ratio Index, the Fibrosis‑4 (FIB‑4) score, and the Nonalcoholic Fatty Liver Disease Fibrosis Score using the existing formulas. The primary outcome was 28‑day mortality. We assessed the associations of these 3 indexes with patient outcomes using logistic regression analysis. In the FIB‑4 sepsis cohort (n = 1560), there was a significant stepwise increase from quartile 1 to quartile 4 in the risk of 28‑day mortality (quartile 1: reference; quartile 2: odds ratio [OR], 1.57, P = 0.06, 95% CI, 0.98-2.515; quartile 3: OR, 2.363, P <0.001, 95% CI, 1.512-3.692; quartile 4: OR, 2.933, P <0.001, 95% CI, 1.895-4.538). The results of multivariable regression, Kaplan-Meier, and Cox regression analyses as well as external validation exhibited good consistency. The FIB‑4 index is associated with 28‑day, 90‑day, and in‑hospital mortality as well as with renal replacement therapy in septic patients without overt chronic liver disease. In other words, an advanced stage of subclinical hepatic fibrosis as represented by the FIB‑4 score indicates poor outcomes in patients with sepsis.

A Sequential Algorithm Combining ADAPT and Liver Stiffness Can Stage Metabolic-Associated Fatty Liver Disease in Hospital-Based and Primary Care Patients.

Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking. Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs, n = 254 and 65) and a population sample (n = 713), were studied. The performance of a recently developed noninvasive algorithm (ADAPT [age, diabetes, PRO-C3 and platelets panel]) as well as aspartate aminotransferase-to-platelet ratio index, fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and LSM was used to stage patients for significant (≥F2) and advanced (≥F3) fibrosis. In the hospital-based cohorts, the N-terminal propeptide of type 3 collagen (Pro-C3) increased with fibrosis stage (P < 0.0001) and independently associated with advanced fibrosis (odds ratio = 1.091, 95% confidence interval [CI]: 1.053-1.113, P = 0.0001). ADAPT showed areas under the receiver operating characteristics curve of 0.831 (95% CI: 0.779-0.875) in the derivation and 0.879 (95% CI: 0.774-0.946) in the validation cohort for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase-to-platelet ratio index, fibrosis-4, BARD (BMI, aspartate aminotransferase to alanine aminotransferase ratio [AAR], diabetes), and nonalcoholic fatty liver disease fibrosis score in most comparisons and comparable with LSM. Serial use of ADAPT and LSM had diagnostic accuracy of 92.5%, with 98% and 100% negative predictive value in the derivation and validation cohorts, respectively. In the population cohort, PRO-C3 associated with advanced fibrosis (P = 0.04), while ADAPT had a negative predictive value of 98% for excluding advanced fibrosis. PRO-C3 and ADAPT reliably exclude advanced fibrosis in low-risk populations. The serial combination of ADAPT with LSM has high diagnostic accuracy with a low requirement for liver biopsy. The proposed algorithm would help stratify those who need biopsies and narrow down those patients who would need to be referred to specialty clinics.

Abstract 12917: Prognostic Value of the Combination of Model for End-stage Liver Disease Excluding Inr Score and Non-alcoholic Fatty Liver Disease Fibrosis Score in Patients Admitted for Acute Heart Failure

Background: Cardiohepatic interactions have been a focus of attention in heart failure(HF), and the model for end-stage liver disease excluding INR (MELD-XI) has been shown to be useful for prediction of poor outcome in patients (pts) with acute decompensated heart failure (ADHF). Furthermore, it has been reported that liver stiffness predicts adverse prognosis in pts with HF. Liver fibrosis is assessed by non-invasive fibrosis markers such as Fibrosis-4 (FIB4) index, non-alcoholic fatty liver disease fibrosis score (NFS) and aminotransferase to platelet ratio index (APRI). Recently, a new group of HF pts with mid-range ejection fraction (HFmrEF) has been defined, separated from reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, there is little information available on the comparison of prognostic significance of MELD-XI and liver fibrosis scores in ADHF pts, relating to LVEF. Methods: We prospectively studied 466 consecutive ADHF pts (HFrEF (LVEF≦40%): n=164, HFmrEF (40&lt;LVEF&lt;50): n=104 and HFpEF (LVEF≧50%): n=198). At the discharge, we calculated MELD-XI, FIB4 index , NFS, and APRI. The endpoint was all cause death (ACD). Results: During a follow-up period of 2.8±1.5 years, 143 pts had ACD. At multivariate Cox analysis, MELD-XI and FIB4 index was independently associated with ACD irrespective of LVEF. The pts with both greater MELD-XI ([HFrEF]≥25.8, [HFmrEF]≥33.2, [HFpEF]≥30.1) and greater FIB4 index ([HFrEF]≥2.58, [HFmrEF]≥2.58, [HFpEF]≥2.22) had a significantly increased risk of ACD than those with either and none of them in all three groups. Conclusions: The combination of MELD-XI and FIB4 index might be useful for stratifying pts at risk for ACD in ADHF pts with irrespective of LVEF.

Abstract 15135: Liver Fibrosis Scores Predict Cardiovascular Outcomes in Patients With Previous Myocardial Infarction

Introduction: Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. Hypothesis: The aim of the present study was to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. Methods: A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs were used including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score in the current study. The CVOs covered major adverse cardiac event (MACE), hard endpoint, cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: During a mean follow-up of 47.4±24.8 months, 431 (11.6%) MACE occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CI) for the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.76 (1.33-2.34), 2.39 (1.71-3.34), 2.46 (1.62-3.74), 1.60 (1.18-2.17) and 1.28 (1.03-1.58), respectively. These LFSs were also independent predictors of hard endpoint, cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. Conclusions: The present study firstly demonstrated that LF scores might affect the prognosis in patients with previous MI, suggesting that LF scores may be helpful to further risk stratification and supporting LF scores screening in patients with previous MI.

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

Abstract Background and aims The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of metabolic risk indicators that may accurately predict residual cardiovascular risk in patients with CAD. Method This is a nested case control study of the post PCI registry from single tertiary hospital. Among 5589 patients who underwent PCI from 2010 through 2014, previously diagnosed 1510 NAFLD patients and 296 consecutive NAFLD patients who had undergone both PCI and ultrasonography of abdomen within 1 year between the tests were enrolled. (median age, 64y (IQR 55–73)). We applied the NFS to the patients at baseline, using validated NFS cut-offs and 201 patients with higher NFS, defined as NFS &amp;gt;0.67 at PCI, were 1:1 matched with controls, based on propensity scores for higher NFS &amp;gt;0.67. Results Higher NFS (NFS &amp;gt;0.67) was more prevalent in patients with left ventricle (LV) dysfuction (LVEF at PCI &amp;lt;40%) than in those without (81.0% vs 33.6%, p&amp;lt;0.001). Baseline higher NFS was significantly associated with LV dysfunction (adjusted OR 1.86, 95% CI 1.36 to 2.55, p&amp;lt;0.001), and baseline higher NFS and persistent higher NFS at 1 year after PCI were independent predictor of a 5-years CV death, after adjustment for LVEF (adjusted HR 1.42, 95% CI 1.03 to 1.95, p=0.023; adjusted HR 1.52, 95% CI 1.08 to 2.64, p=0.033). Conclusion With a longitudinal assessment of the association between NAFLD status by NFS and the risk of CV death, we found post-PCI patients with persistent higher NFS were at higher risk of CV death compared with those without. KM rates of CV death according to NFS Funding Acknowledgement Type of funding source: None

Accuracy of Fibrosis-4 index and non-alcoholic fatty liver disease fibrosis scores in metabolic (dysfunction) associated fatty liver disease according to body mass index: failure in the prediction of advanced fibrosis in lean and morbidly obese individuals.

While non-invasive scores are increasingly being used to screen for advanced fibrosis in metabolic (dysfunction) associated fatty liver disease (MAFLD), the effect of BMI on their clinical utility remains uncertain. This study assessed the usefulness of the Fibrosis-4 index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS) in lean, overweight, obese, severely obese, and morbidly obese patients with biopsy-proven MAFLD. A total of 560 patients (28 lean, 174 overweight, 229 obese, 89 severely obese, 40 morbidly obese) were included. Diagnostic performances and optimal cut-off values for FIB-4 and NFS were calculated using receiver operating characteristic (ROC) curve analysis. In both lean and morbidly obese patients with MAFLD, both FIB-4 and NFS failed to discriminate advanced fibrosis. Conversely, both scores showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients (area under the ROC curve: 0.829, 95% confidence interval: 0.738-0.919). FIB-4 and NFS can confidently be used to exclude advanced fibrosis in overweight, obese, and severely obese patients. However, they do not appear clinically useful in lean and morbidly obese patients.