Higher Fibrosis Research Articles

Itemization difference of patient-reported outcome in patients with chronic liver disease.

Background and aimsThe itemization difference of patient-reported outcome (PRO) in hepatitis patients with different etiologies remains elusive in Asia. We aimed to assess the characteristics and the difference of health-related quality of life (HRQoL) in chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) patients.MethodsWe conducted the study in an outpatient setting. The 36-Item Short Form Health Survey (SF-36) was completed by the patients upon the initial diagnosis and recruitment for a long-term follow-up purpose. The PRO results were also assessed by disease severity.ResultsThere were 244 patients (198 males) of CHB, 54 patients (29 males) of CHC, and 129 patients (85 males) of NAFLD, respectively. CHC patient had the mean score of 67.1 ± 23.3 in physical component summary (PCS) of the SF-36 health survey, which was significantly lower than CHB patients (76.4 ± 19.5), and NAFLD patients (77.5 ± 13.7), respectively (p = 0.001). The significantly lower performance of PCS in CHC patients was mainly attributed to the lower performance in physical functioning and bodily pain components. Higher fibrosis 4 index scores were significantly associated with lower PCS scores in all patient groups. There was no significant difference of mean mental component summary (MCS) between groups. However, NAFLD patients had significantly lower mental health scores than other groups (p = 0.02).ConclusionsThe significant difference of HRQoL exists in hepatitis patients with different etiologies. Disease severity leads to a lower PCS performance.

Poorly Differentiated Hepatocellular Carcinoma: Resection is Equivalent to Transplantation in Patients with Low Liver Fibrosis

Introduction: Organ allocation criteria for liver transplantation (e.g. Milan) focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). Methods: The National Cancer Database was queried between 2004-2016 for solitary HCC meeting Milan criteria undergoing SX vs. LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. Results: 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P<.001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stay, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs. LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. Discussion: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs. LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Severe Hepatic Steatosis Is Associated With Low-Level Viremia and Advanced Fibrosis in Patients With Chronic Hepatitis B in North America.

The obesity epidemic has increased the risk of nonalcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in patients with CHB based on controlled attenuation parameter (CAP) and the epidemiological, clinical, and virological factors associated with severe hepatic steatosis. The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and hepatits B virus (HBV) tests. Liver fibrosis and steatosis were measured by transient elastography and CAP, respectively. Any grade and severe steatosis were defined as CAP >248 and>280 dB/m, respectively. Advanced liver fibrosis was defined as transient elastography measurement >10.7 kPa. In 1178 patients with CHB (median age: 47.4%, 57.7% males, 75.7% Asian, 13% African, 6.5% White, 86% HBV e antigen negative, median HBV DNA of 2.44 log10IU/mL, 42.7% receiving treatment), the prevalence of any grade and severe steatosis was 53% and 36%, respectively. In the multivariate analysis, obesity was a significant predictor for severe steatosis (adjusted odds ratio: 5.046, 95% confidence interval: 1.22-20.93). Severe steatosis was a determinant associated with viral load (adjusted odds ratio: 0.385, 95% confidence interval: 0.20-0.75, P<.01; r=-0.096, P=.007) regardless of antiviral therapy, age, and alanine aminotransferase levels. In this large multiethnic CHB population, hepatic steatosis is common. Severe steatosis is independently associated with higher fibrosis, but negatively with HBV DNA, regardless of antiviral therapy history.

The Relationship between Hepatic High FIB-4 Score and COVID-19 Pneumonia.

We aimed to compare the level of hepatic FIB-4 scores between COVID-19 patients who had pneumonia and COVID-19 patients who had no pneumonia in an attempt to develop a risk assessment after the treatment and recovery of active COVID-19 infection. The study included 80 patients who were consecutively selected and admitted to an internal medicine outpatient clinic for a control examination after COVID-19 infection. Chest tomography was performed on all patients during the COVID-19 infection. Patients were divided into two groups as those with and without lung involvement on CT. COVID-19 infection was diagnosed using real-time reverse transcription-polymerase chain reaction (RT-PCR). The hepatic fibrosis 4 (FIB-4) index score was calculated for each patient. The statistical analyses were performed using Student's t-test and chi-squared tests. We found that the increased hepatic FIB-4 index score in patients with pneumonia group was statistically significant compared to the control group (p < 0.001). The regression analysis showed that the hepatic FIB-4 index has significant prognostic efficiencies in both uni- and multivariate models (p < 0.05). The hepatic FIB-4 index appears to be a simple parameter with a good prognostic value in patients with COVID-19 infection.

Implications of Elevated Fibrosis-4 Index in Patients Receiving Trans-Catheter Aortic Valve Replacement.

Background: The prognostic implication of the fibrosis-4 index, which represents the degree of hepatic injury, on patients receiving trans-catheter aortic valve replacement (TAVR) remains unknown. Methods: Patients who underwent TAVR to treat severe aortic stenosis at our institute between 2015 and 2020 were included in this retrospective study and followed for 2 years from the index discharge. The impact of the fibrosis-4 index, which was calculated using age, hepatic enzymes, and platelet count, on 2-year heart failure readmissions was investigated. Results: A total of 272 patients (median age 85 (82, 88) years old, 76 (28%) men) were included. The median baseline fibrosis-4 index was 2.8 (2.2, 3.7). A high fibrosis-4 index (>3.79) was associated with higher cumulative incidence of the primary endpoint (18% versus 4%, p < 0.001) and higher event rates (0.1041 versus 0.0222 events/year, p < 0.001), with an adjusted hazard ratio of 1.27 (95% confidence interval 1.04–1.54, p = 0.019). Conclusion: an elevated fibrosis-4 index at baseline, indicating the existence of persistent hepatic congestion, was associated with incidences of heart failure following TAVR. Calculating the fibrosis-4 index before TAVR is highly encouraged for risk stratification and shared decision making.

Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study.

Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

Abstract 9610: High Levels of Myeloperoxidase Are Similar Across ASCVD Risk Groups and Are Associated with Markers of Liver Fibrosis and Kidney Function in a Workforce Population

Background: High blood levels of free myeloperoxidase (MPO) identify patients at risk for cardiovascular disease. We investigated levels of MPO according to 10-year ASCVD risk and the association between high MPO and markers of liver fibrosis and kidney disease. Methods: The study included participants in employer-sponsored annual health assessment (August 2020 to March 2021, n=33,984, 63% women, median age 47, IQR 36 to 56). Age and sex adjusted logistic models assessed the association between high MPO and non-alcoholic fatty liver disease (NAFLD) fibrosis score, liver Fibrosis-4 (FIB4) score, and estimated glomerular filtration rate (eGFR), stratified by 10-year ASCVD risk groups. Results: High MPO (&gt;540 pmol/L) was found in 3% (n =925), 4% (n=184), and 5% (n =63) of the low (&lt;7.5%), intermediate (7.5% to 20%), and high (&gt;20% or prevalent disease) ASCVD risk groups, respectively. High MPO (&gt;540 vs. ≤540 pmol/L) was associated with high NAFLD fibrosis score (&gt;0.676 vs. &lt;-1.455): OR = 4.7, 95%CI 3.5 to 6.2, high FIB4 score (&gt;3.25 vs. ≤3.25): OR =3.4, 95%CI 1.8 to 6.4 and low eGFR (&lt;60 vs. ≥60 mL/min/1.73m 2 ): OR =1.8, 95%CI 1.4 to 2.4. The associations varied according to ASCVD risk (Figure). In the high ASCVD risk group, MPO was not associated with either NAFLD fibrosis score, FIB4 score, or eGFR (P ≥0.2 for all) and the risk differed according to ASCVD risk group (&gt;20% vs. ≤20%) for NAFLD fibrosis score (P int =0.03) and eGFR (P int =0.01). Conclusion: The fraction of those with high MPO did not appreciably differ across ASCVD risk groups and most participants with high MPO levels in this workforce population were in the low ASCVD risk group. This observation is consistent with the hypothesis that subjects in the high ASCVD risk group are more likely to be receiving preventive therapies, whereas guidelines dictate that those in moderate and low risk groups may not. Investigating the association of MPO levels in ASCVD risk groups according to preventive therapy intensity is warranted.

The Liver and Heart: How the Two Most Beloved “Babies” in the Human Body Communicate

The Liver and Heart: How the Two Most Beloved “Babies” in the Human Body Communicate

Liver Fibrosis Scoring Systems as Novel Tools for Predicting Recurrent Cardiovascular Events in Patients with a Prior Cardiovascular Event

Abstract Objective: Regarding the secondary prevention of cardiovascular disease (CVD), there is great interest in preventing recurrent cardiovascular events (RCVEs). The prognostic importance of liver fibrosis scores (LFSs) has previously been reported in various CVDs. We hypothesized that LFSs might also be useful predictors for RCVEs in patients with prior cardiovascular events (CVEs). Herein, we aimed to evaluate the associations of LFSs with RCVEs in a large, real-world cohort of coronary artery disease (CAD) patients with a prior CVE. Methods: In this multicenter prospective study, 6527 consecutive patients with angiography-diagnosed CAD who had experienced a prior CVE (acute coronary syndrome, stroke, percutaneous coronary intervention, or coronary artery bypass grafting) were enrolled. LFSs were computed according to the published formulas: non-alcoholic fatty liver disease fibrosis score (NFS) includes age, body mass index (BMI), impaired fasting glycemia or diabetes mellitus (DM), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, platelets, and albumin; fibrosis-4 (FIB-4) includes age, AST, ALT, and platelets; Forns score includes age, gamma-glutamyltransferase (GGT), and platelets; BARD includes BMI, AST/ALT ratio, and DM; GGT/platelet ratio includes GGT and platelets; AST/ALT ratio includes AST and ALT; and AST/platelet ratio index includes AST and platelets. The originally reported cutoffs were used for the categorization of low-, intermediate-, and high-score subgroups. All patients were followed up for the occurrence of RCVEs (comprising cardiovascular death, non-fatal myocardial infarction, and stroke). Cox and Poisson regression analyses were used to assess the relationship of baseline LFSs with the risk of RCVE. Results: During a mean follow-up of (54.67 ± 18.80) months, 532 (8.2%) RCVEs were recorded. Intermediate and high NFS, FIB-4, Forns, and BARD scores were independently associated with an increased risk of RCVE (hazard ratios ranging from 1.42 to 1.75 for intermediate scores and 1.35 to 2.52 for high scores). In the subgroup analyses of sex, age, BMI, DM, and hypertension status, the increased risk of RCVEs with high LFSs (NFS, FIB-4, Forns, and BARD) was maintained across the different subgroups (all P &lt; 0.05). Conclusion: This study showed that LFSs are indeed independently associated with RCVEs, suggesting that LFSs may be used as novel tools for risk stratification in CAD patients with a prior CVE.

High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study.

BackgroundBased on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.MethodsThis multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.ResultsThe patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.ConclusionBoth DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

Muscle Inflammation Susceptibility: A Potential Prognostic Factor For Optimal Post-surgical Rehabilitation

Many individuals with end-stage osteoarthritis undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain and improve mobility and quality of life. However, ~35% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt pro-inflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some TKA/THA patients. PURPOSE: We are interrogating the hypotheses that a) MuIS+/- status will result in a differential perioperative expression profile that may partially explain low functional outcomes, and b) resistance training rehabilitation will more effectively overcome MuIS+ status than usual care for successful recovery post-surgery. METHODS: Muscle, serum, and functional data were leveraged from our ongoing two-site, randomized, controlled trial (N = 75 randomized). Participants were dichotomized based on surgical (SX) muscle gene expression of TNFRSF1A (TNFαR). MuIS+/- samples were probed for transcript expression and indices of skeletal muscle integrity. Preliminary perioperative comparisons were made using two-tailed T-tests; alpha P < 0.05. Preliminary miRNA-seq data were analyzed using Partek Flow; differentially expressed (DE) miRNAs were defined as Fold change (FC) ≥ 1.5 and P ≤ 0.05. RESULTS: 70 participants (27 M/43F; mean age 62 ± 9 yrs; mean BMI 31.3 ± 4.9 kg/m2) undergoing THA/TKA were clustered as MuIS+ (n = 24) or MuIS- (n = 46). MuIS+ muscle exhibited significantly higher pro-inflammatory (IL-6R) and catabolic (TRIM63) gene expression (P = 0.0001 and 0.03, respectively) compared to MuIS-. Further, significantly lower skeletal muscle integrity exists on the SX vs non-SX limb, illustrated by 20% higher fibrosis (P = 0.0003), and 3.5% lower thigh muscle mass (P = 0.005). Preliminary serum miRNA-seq (for N = 9) indicate 193 DE miRNAs (P ≤ 0.05, FC ≥ 1.5) following the intervention. CONCLUSIONS: Preliminary results suggest MuIS+ patients exhibit more inflammation and catabolic signaling in skeletal muscle of the SX limb, accompanied by decreased skeletal muscle integrity. This highlights the profound impact of MuIS+ status and emphasizes the potential value of perioperative MuIS assessment to inform optimal post-surgical care. Funding: T32HD071866, R01HD084124

Clinical Significance of the Fibrosis-4 Index in Patients with Acute Heart Failure Requiring Intensive Care.

The Fibrosis-4 (FIB4) index could indicate the liver fibrosis in patients with chronic hepatic diseases. It was calculated using the following formula: (age × aspartate aminotransferase [U/L]) / (platelet count [103/μL] × √alanine aminotransferase [U/L]). However, the clinical impact of the FIB4 index in the acute phase of acute heart failure (AHF) has not been sufficiently investigated.A total 1,468 AHF patients were analyzed. The median FIB4 index was 2.71 [1.85-4.22]. The patients were divided into three groups according to the quartiles of their FIB4 index (low-FIB4 [Q1, ≤ 1.847], middle-FIB4 [Q2/Q3, 1.848-4.216], and high-FIB4 [Q4, ≥ 4.216] groups). A Kaplan-Meier curve analysis showed that the prognosis, such as all-cause mortality and HF events within 365 days, was significantly poorer in the high-FIB4 group than in the middle-FIB4 and low-FIB4 groups. A multivariate Cox regression model identified high FIB4 index as an independent predictor of 365-day all-cause death (hazard ratio (HR): 1.660, 95% CI: 1.136-2.427) and HF events (HR: 1.505, 95% CI: 1.145-1.978). The multivariate logistic regression analysis showed that the high plasma volume status (PVS) (Q4, odds ratio [OR]: 2.099, 95% CI: 1.429-3.082), low systolic blood pressure (SBP) (< 100 mmHg, OR: 3.825, 95% CI: 2.504-5.840), and low left ventricular ejection fraction (< 40%, OR: 1.321, 95% CI: 1.002-1.741) were associated with a high FIB4 index.A high FIB4 index can predict adverse outcomes in AHF patients, which indicate that congestive liver and liver hypoperfusion occur due to low cardiac output in the acute phase of AHF.

Risk stratification of anastomotic leakage using eGFR and FIB-4 index in patients undergoing esophageal cancer surgery

Renal insufficiency and liver cirrhosis are identified as independent risk factors for anastomotic leakage (AL) after esophagectomy. However, research evaluating the incidence of AL using quantitative data to measure renal function and liver fibrosis remain to be limited. Therefore, this study was conducted to evaluate postoperative AL after esophagectomy using estimated glomerular filtration rate (eGFR) and fibrosis-4 (FIB-4) index. In total, 184 patients who underwent esophagectomy were included in this study; then, they were divided into the non-AL group (n = 161) and AL group (n = 23), after which their background data and intraoperative and postoperative outcomes were compared. In addition, risk factors for AL were evaluated using a logistic regression model. Preoperative body mass index of ≥21.5kg/m2, hemoglobin A1c level of ≥7.3%, FIB-4 index of ≥1.44, and eGFR of <59ml/min/1.73m2 were found to be significantly frequent in the AL group compared with the non-AL group. Multivariate analysis revealed FIB-4 index of ≥1.44 (p = 0.013; OR, 3.780; 95% CI, 1.320-10.800) and eGFR of <59ml/min/1.73m2 (p = 0.018; OR, 3.110; 95% CI, 1.220-8.020) as the independent risk factors for AL. In addition, we stratified the patients into three groups based on the incidence of AL as follows: low risk (5.5%, low FIB-4 index), intermediate risk (13.0%, high FIB-4 index and eGFR), and high risk (37.5%, high FIB-4 index and low eGFR). Preoperative eGFR and FIB-4 index were found to be useful markers to predict AL after esophagectomy.

Impact of Fibrosis-4 Index Prior to COVID-19 on Outcomes in Patients at Risk of Non-alcoholic Fatty Liver Disease.

BackgroundSeverity of disease and outcomes in patient with COVID-19 has been associated with several risk factors tied to the metabolic syndrome.AimsWe conducted a study with the objective of describing the association between the baseline Fibrosis-4 (FIB-4) index prior to SARS-CoV-2 infection and the severity of COVID-19 among patients at risk of non-alcoholic fatty liver disease (NAFLD).MethodsThis was a retrospective cohort study of patients with at least two risk factors for metabolic syndrome diagnosed with COVID-19. The main exposure of interest was FIB-4 index prior to infection, categorized into three previously validated age-specific levels. The main outcomes of interest were disease requiring hospitalization and in-hospital mortality.ResultsWe included 373 patients [median age, 62 years; 194 male (52%); median number of metabolic syndrome risk factors, 3]. The median FIB-4 index was 1.10 (interquartile range 0.78–1.61). In models adjusting for diabetes mellitus and chronic kidney disease, patients with intermediate FIB-4 index had 67% higher odds of hospitalization compared to those in the low category {odds ratio (OR) 1.67 [(95% CI 1.06–2.64); p = 0.03]} and patients with high FIB-4 index had higher odds of mortality compared to intermediate and low category with an OR 2.22 (95% CI 1.20–4.12; p = 0.01). However, when we evaluated components of FIB-4 (age and AST/ALT ratio), we found that age alone was the best predictor of hospitalization and mortality.ConclusionsAmong patients at risk of NAFLD with COVID-19 infection, elevated pre-infection FIB-4 index was associated with worsened clinical outcomes, but age was the strongest predictor.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10620-021-07120-0.

Preoperative Fibrosis-4 (FIB-4) Evaluation May Be Helpful to Evaluate Prognosis of Gastric Cancer Patients Undergoing Operation: A Retrospective Study.

BackgroundLiver dysfunction and chronic inflammation influence the prognosis of many tumors and surgical outcomes. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, originally defined as a noninvasive fibrosis marker, can predict the prognosis of patients with gastric cancer undergoing radical gastric cancer surgery.MethodsWe have retrospectively analyzed 594 consecutive patients with gastric cancer who underwent gastrectomy in our database. The FIB-4 index was calculated using laboratory data and age before gastrectomy. The clinical utility of FIB-4 was evaluated by X-tile. Patients were divided into two groups (high and low FIB-4 index groups), and their overall survival (OS) was investigated. Cox regression analysis was used to identify the independent parameters associated with prognosis. Finally, we developed a prognostic prediction model by using R statistical software.ResultsA total of 556 patients, including 422 men and 134 women, were enrolled. Of these, 61 (11.0%) and 495 (89.0%) patients had low and FIB-4 indexes, respectively. In addition to the indicators of FIB-4, preoperative age, tumor site, surgical procedure, TNM stage, and postoperative complications were found to be independent predictors of prognosis (P < 0.05). Among patients, the FIB-4 index group had significantly shorter OS (log-rank P = 0.01) than the low FIB-4 index group. This association was also confirmed in the multivariate analysis (hazard ratio, 4.65; 95% confidence interval, 1.07-4.29; P = 0.031).ConclusionsPreoperative FIB-4 index can predict long-term outcomes of gastric cancer patients who had undergone gastrectomy.

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.

Predictors of Sarcopenia in an Obese Asian Population

Sarcopenia is associated with obesity and might also be responsible for other disorders. Here, we investigated the prevalence of sarcopenia and its predictors in obese subjects. Subjects who underwent a medical health checkup and living-related liver donors were recruited. Obesity was defined as body mass index (BMI) ≥25 kg/m2. Muscle mass was assessed using computed tomography at the 3rd lumbar vertebra. The lowest quartile of the lumbar skeletal muscle index (LSMI) was considered sarcopenia. Among 466 obese subjects, 53 (11.4%) had sarcopenia. Subjects with sarcopenia were significantly older (mean 66.6 vs. 53.3 years) and had a significantly higher prevalence of hypertension (62.3 vs. 46.0%) and diabetes (45.3 vs. 31.0%), higher fibrosis-4 (FIB-4) index (mean 1.57 vs. 1.16), and higher atherosclerotic cardiovascular disease (ASCVD) risk score (mean 22.86% vs. 11.15%), whereas they had a significantly lower prevalence of female gender (13.2% vs. 27.8%), lower BMI (mean 26.4 vs. 27.4 kg/m2), and lower LSMI (mean 43 vs. 56 cm2/m2) than subjects without sarcopenia (all P < 0.05). On multivariate analysis, higher BMI (odd ratio [OR] = 0.599, P = 0.001) was independently associated with a reduced risk of sarcopenia, whereas higher ASCVD risk scores (OR = 1.045, P < 0.001) were independently associated with an increased risk of sarcopenia. Sarcopenia is significantly associated with lower BMI and higher cardiovascular risk in an obese Asian population.

A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation

Nonalcoholic Fatty Liver Disease and Fibrosis Risk in Patients With Obstructive Sleep Apnea: A Retrospective Analysis.

ObjectivesObstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are prevalent and commonly associated conditions. We aimed to estimate the prevalence of NAFLD and identify liver fibrosis risk using noninvasive scoring methods in a cohort of patients with OSA.MethodologyIn this retrospective study of patients with confirmed OSA, patients who underwent abdominal ultrasonography were recruited. The primary outcome was the prevalence of suspected NAFLD (steatosis on ultrasound and/or elevated alanine transaminase [ALT]). The secondary outcomes included the prevalence and predictors of liver fibrosis risk as assessed by the NAFLD fibrosis score (NFS) and fibrosis-4 (FIB-4) score.ResultsA total of 133 patients fulfilled the study inclusion criteria. The average age was 49.8±15.1 years, and 57.1% were females. The average BMI was 37.3±14.5. According to the apnea-hypopnea index (AHI) scores, 37.9%, 29.6%, and 32.6% of participants had mild (5-14), moderate (15-29), and severe (>=30) OSA, respectively. Radiologically defined NAFLD was detected in 44.4% of the participants, and elevated liver enzymes were detected in 63.9% of the patients. High NFS and FIB-4 scores were recorded in 9% and 3.8% of the patients, respectively. According to logistic regression analysis, age and BMI significantly predicted high NFS scores.ConclusionNAFLD appears to be common among OSA patients. Age and obesity, but not OSA severity, predicted high liver fibrosis risk as assessed by noninvasive scoring systems.

Multimodality approach by cardiac magnetic resonance and biological markers in left ventricular non-compaction with heart failure with preserved ejection fraction - revealing the unknown

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PN-III-P1-1-TE-2016-0669, within PNCDI III Background Left ventricular non-compaction (LVNC) is associated with an increased risk of heart failure (HF). The presence of a real LVNC with HF with preserved ejection fraction (HFpEF), is still controverted. Methods We evaluated prospectively 42 patients with HFpEF, 21 with LVNC (61 ± 9 years) and 21 without LVNC (LVC), aged and risk factor matched, by cardiac magnetic resonance (CMR) 1.5T. LVNC diagnosis was confirmed by Petersen and Jacquier criteria (NC/C ratio and the percentage of NC myocardium). We performed myocardial T1 mapping (normal value of 950 ± 21ms). We calculated a mean value of all native T1 (T1mean), and also for apical (apicalT1) and basal segments (basalT1). We also calculated ECV mean, basal and apical. All patients had NTproBNP and biomarkers for systemic inflammation (hsCRP, IL6, cystatin C and sST2), endothelial dysfunction: VCAM, von Willebrand factor (vWf), vWF metalloproteinase-ADAMTS13, and myocardial fibrosis: vascular peroxidase (VPO), and Galectin-3. Results In the LVNC, mean NC/C ratio was 2.9 ± 0.5 mm and the percentage of NC myocardium was 24.41 ± 8.8%. LVNC patients had significantly higher T1apical, higher ECVmean, ECV basal and apical (Table) by comparison with LVC group, suggesting an extensive fibrosis in LVNC group with significantly higher apical fibrosis. Inflammatory markers were similar between groups, LVNC patients had lower values of ADAMTS13, suggesting endothelial dysfunction, and higher values of Galectin-3, suggesting increased myocardial fibrosis (Table). Galectin-3 correlated positively only with apicalT1 (R = 0.49, p = 0.04). NTproBNP significantly correlated with VPO, a promotor of fibrosis (r = 0.61, p = 0.009) in LVNC group, whereas in LVC group correlated with cystatin C (r = 0.62, p = 0003) and VCAM (r = 0.4, p = 0.05). Native apical T1 cut off &amp;gt;1021 ms provided the highest sensibility and specificity to differentiate segments with and without NC in HFpEF (p = 0.002) (Figure). Conclusion HFpEF patients with LVNC have significant higher NTproBNP, higher fibrosis than patients without LVNC, more extensive in non-compacted apical segments. Galectin-3 level correlates only with apical fibrosis on CMR, expressed by apicalT1 time. Moreover, endothelial dysfunction seems to play an important role in HFpEF generation in LVNC. All findings suggests that LVNC is a stand alone condition, not an adaptive hyper-trabeculation in HFpEF. Table.Comparison between groups NTproBNP (pg/ml) Galectin3 (ng/ml) ADAMTS13 (ng/ml) T1mean (ms) basalT1 (ms) apicalT1 (ms) ECV mean (%) ECV basal (%) ECV apical (%) LVNC 294 ± 282 8.44 ± 3.45 767.35 ± 335.56 1013.8 ± 31.8 1002.8 ± 27.2 1059 ± 73 27.2 ± 2.9 26.2 ± 2.9 29.6 ± 3.9 LVC 163 ± 71 6.67 ± 2.88 962.33 ± 253.78 1003.2 ± 28.1 1004.3 ± 29.5 1007 ± 40 24.3 ± 2.5 24.2 ± 2.7 25.2 ± 2.8 P value 0.031 0.048 0.049 0.26 0.865 0.007 0.002 0.033 &amp;lt;0.001 Abstract Figure