High Fibrosis-4 Index Research Articles

FIB-4 index and liver fibrosis are risk factors for long-term outcomes in atrial fibrillation-related stroke

ObjectiveLiver fibrosis (LF) is associated with a poor prognosis in patients with ischemic stroke (IS). We aimed to assess whether LF affects long-term outcomes in patients with atrial fibrillation-related stroke or such effects vary according to sex. MethodsWe conducted a multicenter prospective cohort study of Korean patients with atrial fibrillation-related IS. We calculated the fibrosis-4 (FIB-4) index, and LF degree was categorized into two groups (non-advanced vs. advanced) based on the FIB-4 index. Recurrent IS, major adverse cardiac events (MACEs), and all-cause mortality were evaluated using Cox proportional hazard model. ResultsA total of 2897 patients were included; the median age was 75 (interquartile range 68–80) years, and 51.8% were men. The median follow-up period was 16.3 months. Of these patients, 23% had advanced LF indicated by FIB-4 index. Multivariable analysis in all populations demonstrated that the FIB-4 index and advanced LF were significantly associated with MACEs and all-cause mortality but not with recurrent IS. Furthermore, a sex disparity was observed in the outcomes of the patients. A high FIB-4 index in men was a significant predictor of recurrent IS [subdistribution hazard ratio (95% confidence interval): 1.08 (1.02–1.14)]. However, the significance of advanced LF disappeared in MACEs in women and in all-cause mortality in men. ConclusionThe FIB-4 index and advanced LF indicated by FIB-4 index are independent prognostic factors for long-term outcomes in Asian patients with atrial fibrillation-related IS. However, these predictors may contribute differently to patient outcomes depending on the sex.

Type III procollagen peptide level can indicate liver dysfunction associated with volume overload in acute heart failure.

AimThe role of serum type III procollagen peptide (P3P) level in the acute phase of acute heart failure (AHF) requires clarification. We hypothesized that serum P3P level is temporarily higher during the acute phase, reflecting liver dysfunction due to congestion.Methods and resultsA total of 800 AHF patients were screened, and data from 643 patients were analysed. Heart failure was diagnosed by the treating physician according to the European Society of Cardiology (ESC) guidelines, and included patients being treated with high‐concentration oxygen inhalation (including mechanical support) for orthopnea, inotrope administration, or mechanical support for low blood pressure, and various types of diuretics for peripheral or pulmonary oedema. In all cases, diuretics or vasodilators were administered to treat AHF. The patients were divided into three groups according to their quartile (Q) serum P3P level: low‐P3P (Q1, P3P ≤ 0.6 U/mL), mid‐P3P (Q2/Q3, 0.6 < P3P <1.2 U/mL), and high‐P3P (Q4, P3P ≥ 1.2 U/mL). The plasma volume status (PVS) was calculated using the following formula: ([actual PV − ideal PV]/ideal PV) × 100 (%). The primary endpoint was 365 day mortality. A Kaplan–Meier curve analysis showed that prognoses, including all‐cause mortality and heart failure events within 365 days, were significantly (P < 0.001) worse in the high‐P3P group when compared with the mid‐P3P and low‐P3P groups. A multivariate logistic regression analysis showed that high PVS (Q4, odds ratio [OR]: 4.702, 95% CI: 2.012–20.989, P < 0.001), high fibrosis‐4 index (Q4, OR: 2.627, 95% CI: 1.311–5.261, P = 0.006), and low estimated glomerular filtration rate per 10 mL/min/1.73 m2 decrease (OR: 1.996, 95% CI: 1.718–2.326, P < 0.001) were associated with high P3P values. The Kaplan–Meier curve analysis demonstrated a significantly lower survival rate, as well as a higher rate of heart failure events, in the high‐P3P and high‐PVS groups when compared with the other groups. A multivariate Cox regression model identified high P3P level and high PVS as an independent predictor of 365 day all‐cause mortality (hazard ratio [HR]: 2.249; 95% CI: 1.081–3.356; P = 0.026) and heart failure events (HR: 1.586, 95% CI: 1.005–2.503, P = 0.048).ConclusionA high P3P level during the acute phase of AHF served as a comprehensive biomarker of liver dysfunction with volume overload (i.e. liver congestion) and renal dysfunction. A high P3P level at admission may be able to predict adverse outcomes in AHF patients.

Abnormal liver tests and non-alcoholic fatty liver disease predict disease progression and outcome of patients with COVID-19

Background and aimsCoronavirus disease 2019 (COVID-19) is a serious public health issue that became rapidly pandemic. Liver injury and comorbidities, including metabolic syndrome, are associated with severe forms of the disease. This study sought to investigate liver injury, clinical features, and risk factors in patients with mild, moderate, and severe COVID-19. MethodsWe retrospectively included all consecutive patients hospitalized with laboratory-confirmed COVID-19 between February, 22 and May 15, 2020 at the emergency rooms of a French tertiary hospital. Medical history, symptoms, biological and imaging data were collected. ResultsAmong the 1381 hospitalizations for COVID-19, 719 patients underwent liver tests on admission and 496 (68.9%) patients displayed abnormal liver tests. Aspartate aminotransferase was most commonly abnormal in 57% of cases, followed by gamma-glutamyl transferase, alanine aminotransferase, albumin, alkaline phosphatase, and total bilirubin in 56.5%, 35.9%, 18.4%, 11.4%, and 5.8%. The presence of hepatocellular type more than 2xULN was associated with a higher risk of hospitalization and a worse course of severe disease (odd ratio [OR] 5.599; 95%CI: 1.27–23.86; p = 0.021; OR 3.404; 95% CI: 2.12–5.47; p < 0.001, respectively). A higher NAFLD fibrosis score was associated with a higher risk of hospitalization (OR 1.754; 95%CI: 1.27–2.43, p < 0.001). In multivariate analyses, patients with high fibrosis-4 index had a 3-fold greater risk of severe disease (p < 0.001). ConclusionAbnormal liver tests are common in patients with COVID-19 and could predict the outcome. Patients with non-alcoholic fatty liver disease and liver fibrosis are at higher risk of progressing to severe COVID-19.

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.

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.

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.

FIB-4 index associated with mortality risk of patients with systemic lupus erythematosus: a large retrospective cohort study

IntroductionA considerable proportion of patients with systemic lupus ery­thematosus (SLE) have liver enzyme abnormalities. We evaluated whether fibrosis-4 (FIB-4) was associated with increased mortality of SLE patients.Material and methodsA multicenter retrospective cohort study was conducted based on medical records of first-admission SLE patients who were hospitalized during 1999–2009 in Jiangsu province. FIB-4 was estimated by age, platelet (PLT) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and FIB-4. A Cox model and a restricted cubic spline (RCS) model were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI).ResultsDuring up to 15 years of follow-up, 226 deaths were observed among 2331 SLE patients. Increased overall mortality was associated with abnormal groups of PLT, ALT, AST, and high FIB-4 (≥ 1.92), with adjusted HRs (95% CI) of 1.58 (1.19–2.11), 1.54 (1.14–2.07), 1.58 (1.17–2.12), and 1.88 (1.42–2.50), respectively. Moreover, significant dose-response relationships were found between mortality of SLE and those indexes, and it was nonlinear for PLT (p &lt; 0.001), ALT (p = 0.046) and FIB-4 (p &lt; 0.001), but not AST (p = 0.109). In cause-specific analyses, high FIB-4 index was directly associated with death from liver failure and indirectly associated with other death from infection and neuropsychiatric impairment. We found no significant differences of areas under curves (AUCs) between FIB-4 index and the disease activity index score of SLE.ConclusionsThis is the first report to describe the nonlinear association between FIB-4 index and increased mortality of SLE patients. The FIB-4 index may be used as an independent prognostic indicator for SLE patients.

Fibrosis-4 index as a predictor for mortality in hospitalised patients with COVID-19: a retrospective multicentre cohort study

ObjectiveThe reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with...

Fibrosis-4 Index, a Noninvasive Fibrosis Marker, Predicts Survival Outcomes After Hepatectomy for Colorectal Cancer Liver Metastases.

Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39-3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3months, log-rank p = 0.047) and OS (23.9 vs. 55.0months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46-12.6; p = 0.008). Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose.

Background/AimsSofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection.MethodsFrom January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention-to-treat (ITT) and per-protocol (PP) analyses.ResultsThe mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatment-experienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT 95.5% and 92.3%, PP 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea.ConclusionsSOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Gamma-glutamyl transpeptidase-to-platelet ratio and the fibrosis-4 index in predicting hepatitis B virus-related hepatocellular carcinoma development in elderly chronic hepatitis B patients in China: A single-center retrospective study.

Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and fibrosis-4 (FIB-4) index have been reported to be useful predictors in predicting hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients. However, their predictive performances on HCC development have not been validated in elderly patients. Thus, the aim of this study was to evaluate the predictive values of the GPR and FIB-4 index on HCC in elderly CHB patients with in China.Between January 2007 and December 2016, 1011 CHB patients older than 60 years were enrolled in the study, and their data were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cutoff points of GPR and the FIB-4 index. Cumulative HCC incidence rates were calculated by the Kaplan–Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to detect risk factors for HCC development. The prediction performances of GPR and FIB-4 index were compared based on time-dependent ROC analyses.After a median follow-up of 6.8 (interquartile range 3.9–8.4) years, 39 (3.9%) patients developed HCC. The ROC analysis of GPR and the FIB-4 index at the 5-year time point revealed that the optimal cutoff point was 0.23 for GPR and 4.15 for the FIB-4 index. When stratified by low and high GPR values and FIB-4 indices, the patients’ subgroups showed significantly different cumulative incidences of HCC. The multivariate analysis revealed that high GPR (hazard ratio [HR] 4.224; 95% confidence interval [CI] 1.891–9.434, P < .001) was an independent risk factor for HCC development, whereas a high FIB-4 index was not (HR 0.470; 95% CI 0.212–1.043; P = .063). In the time-dependent ROC analysis, GPR showed higher area under curve (AUC) values than the FIB-4 index did at all time points and reached statistical significance at the 5-, 7-, and 10-year time points (GPR vs FIB-4 index, AUC 0.725 vs 0.549 at 5 years, P = .005; GPR vs FIB-4 index, AUC 0.733 vs 0.578 at 7 years, P = .001; GPR vs FIB-4 index, AUC 0.837 vs 0.475 at 10 years, P < .001).In conclusion, our study suggests GPR is superior to the FIB-4 index in predicting HCC development in elderly CHB patients in China.

P5410Combination assessment of renal and hepatic dysfunction improves the predictability of prognosis in patients with acute decompensated heart failure

Abstract Background Renal dysfunction is associated with poor mortality in patients with heart failure (HF). Hepatic dysfunction, assessed by Fibrosis-4 (FIB4) index, has also prediction ability in acute decompensated HF (ADHF) patients. We investigated whether the assessment of the combination of FIB4 index and renal dysfunction improves predictability in patients with ADHF. Methods We retrospectively enrolled consecutive 758 patients who admitted due to ADHF from January 2011 to February 2018 and followed up for one year. FIB4 index on admission was calculated by the formula: age (yrs) × AST[U/L] / (platelets [103/μL] × (ALT[U/L])1/2). Study subjects were divided into high FIB4 index (&gt;3.25) and low FIB4 index (≤3.25), furthermore each group were classified by the presence/absence of CKD (estimated glomerular filtration rate &lt;60 ml/min/1.73m). We have generated four groups; low FIB4/without CKD (n=154), low FIB4/with CKD (n=294), high FIB4/without CKD (n=56), and high FIB4/with CKD (n=254). The primary outcome was defined as all-cause mortality in one year. We performed Kaplan-Meyer analysis and multivariable Cox regression models. Furthermore, we evaluated the incremental value with C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) when FIB4 index and renal dysfunction added to a baseline model. Results In total, 106 patients died in one year. High FIB4 index and CKD showed significantly higher 1-year mortality (high FIB4 index: 19.7% vs 10.3%, p&lt;0.001, CKD: 17.0% vs 6.7%, p&lt;0.001, respectively). Kaplan-Meyer analysis shows that high FIB4 index with CKD showed statistically higher mortality than the others (vs low FIB4/without CKD, p&lt;0.001, vs high FIB4/without CKD, p=0.031, vs low FIB4/with CKD, p&lt;0.001, respectively). Multivariate Cox regression model revealed that both high FIB4 index and CKD were an independent risk predictor of 1-year mortality (FIB4 index: p&lt;0.001, HR 1.06, 95% CI 1.035–1.087, CKD: p=0.004, HR 1.834, 95% CI 1.213–2.773, respectively) in patients with ADHF. A baseline model for prediction of 1-year mortality was determined by multivariable logistic regression including age, body mass index, systolic blood pressure, and serum albumin (C-index: 0.688). Adding high FIB4 index and CKD to the baseline model, all of C-index (0.738, p=0.04), NRI (0.122, p=0.067), and IDI (0.024, p=0.004) were improved. Receiver operating characteristic curves Conclusions Combination assessment of renal and hepatic dysfunction could improve the predictability of prognosis in patients with ADHF. Acknowledgement/Funding None

Alcoholic and Nonalcoholic Fatty Liver Disease and Incident Hospitalization for Liver and Cardiovascular Diseases

We compared the associations of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (AFLD) with risk of incident hospitalization for liver and cardiovascular diseases. We collected data from the Kangbuk Samsung Health Study on 218,030 men and women in Korea who underwent a health examination from 2011 through 2016. Fatty liver disease (FLD) was detected by ultrasound during the initial examination. The Fibrosis-4 index was used to identify individuals with liver fibrosis. Participants were followed up for as long as 5.9 years and data on hospitalizations for liver and cardiovascular diseases were collected. The prevalence of NAFLD was 22.0% and the prevalence of AFLD was 6.4%. Over a median follow-up period of 4.2 years, we observed 51 and 1097 incident cases of liver disease- or cardiovascular disease-related hospitalizations, respectively. After adjustment for potential confounders, the multivariable-adjusted hazard ratios for liver disease-related hospitalization, comparing NAFLD and AFLD with the reference category (no excessive alcohol intake and no FLD), were 1.73 (95% CI, 0.76-3.96) and 5.00 (95% CI, 2.12-11.83), respectively. The corresponding hazard ratios for cardiovascular disease hospitalization were 1.20 (95% CI, 1.02-1.40) and 1.08 (95% CI, 0.86-1.34), respectively. Among participants with FLD, the risk of liver disease-related hospitalization increased with high Fibrosis-4 index scores, whereas the risk of incident cardiovascular disease did not. In a large cohort study, we found an increased risk of liver disease-related hospitalizations for patients with NAFLD or AFLD, especially among those with Fibrosis-4 index scores. An increased risk of cardiovascular disease-associated hospitalization was observed in patients with NAFLD but not AFLD.

High sex hormone-binding globulin concentration is a risk factor for high fibrosis-4 index in middle-aged Japanese men.

Low endogenous testosterone and sex hormone-binding globulin (SHBG) concentrations have been reported to be associated with metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationships between testosterone or SHBG and liver fibrosis in NAFLD. Thus, we aimed to clarify the relationships between serum testosterone or SHBG concentration and fibrosis-4 (FIB-4) index, a marker of liver fibrosis. Serum testosterone was assayed in various forms (total testosterone [TT], calculated free testosterone [cFT], calculated bioavailable testosterone [cbT], and SHBG) and metabolic markers were also measured in 363 Japanese men (mean age 51.1 ± 8.7 years) at routine health examinations. We then attempted to identify the factors contributing to liver fibrosis by investigating the associations between the metabolic markers, including testosterone, and FIB-4 index. People with a relatively high FIB-4 index (≥1.3) demonstrated lower cFT, cbT, homeostasis model assessment (HOMA)-β, low-density lipoprotein-cholesterol, and blood urea nitrogen, but higher SHBG, than those with a lower FIB-4 index (<1.3). There were no significant differences in HbA1c, fasting glucose concentration, HOMA-R, or metabolic syndrome prevalence between the two groups. Binary regression analysis revealed that SHBG ≥52 nmol/L and cFT <8.0 ng/dL were statistically significant risk factors for FIB-4 index ≥1.3. Receiver operating characteristic analysis revealed that cFT <7.62 ng/dL (area under the curve [AUC] = 0.639) and SHBG ≥49.8 nmol/L (AUC = 0.649) were the strongest risk factors for FIB-4 index ≥1.3. In contrast to previous findings showing low SHBG concentrations in NAFLD, we provide evidence that high SHBG and low bioactive testosterone are associated with liver fibrosis.

Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection.

The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed. During the median observation period of 537days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%. A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.

Profile and value of FIB‐4 in patients with dual chronic hepatitis C and B

Patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are at risk of developing adverse outcomes. Coinfection with both viruses may further increase the risk. Currently, little is known about the role of fibrosis-4 (FIB-4) index, a simple liver fibrosis stage biomarker, in predicting the clinical outcomes. We retrospectively enrolled 152 non-cirrhotic patients with dual chronic HCV and HBV infection: 56 patients received pegylated interferon/ribavirin therapy, while 96 patients remained untreated. The association between the FIB-4 index and the incidence of liver cirrhosis and hepatocellular carcinoma (HCC) was explored. After a 9.88-year follow-up, the incidence of hepatitis B surface antigen seroclearance was 4.97 (95% confidence interval: 3.13-7.89) per 100 person-years in the treated group and was 1.77 (1.10-2.85) in the untreated group. Of the treated group, only three and six patients developed HCC and liver cirrhosis, respectively, while 17 and 23 patients developed HCC and liver cirrhosis, respectively, in untreated group. Baseline FIB-4 index correlated with the development of liver cirrhosis in multivariable analysis of all subjects. High baseline FIB-4 index (per 1 point increase) in the treated groups was associated with a higher risk of developing liver cirrhosis (P=0.001) and HCC (P=0.038) in univariable analysis. FIB-4 index decreased only in the treated group who achieved sustained virological response (n=34, FIB-4 index decreasing from 1.84 to 1.55). In Taiwanese patients coinfected with HCV and HBV, FIB-4 index helps identify patients at risk of developing adverse events, even in patients receiving pegylated interferon/ribavirin therapy.

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents.

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.