FIB-4 Values Research Articles

Investigating the influence of possible liver fibrosis on mortality in patients with coronary artery disease - a post-hoc ISCHEMIA trial analysis

Abstract Background There is a plethora of studies demonstrating that comorbidities (e.g., diabetes and renal dysfunction) directly influence outcomes in patients undergoing PCI or CABG for coronary artery disease (CAD). Yet, liver dysfunction is not really included in current risk assessment beyond the presence of liver cirrhosis. Retrospective single center evidence now suggests that the presence of liver fibrosis may be an indicator of elevated risk. Using the FIB-4 score, where increasing values correlate with increaseing degrees of histological liver fibrosis, liver fibrosis could already be detected with all required laboratory values (AST, ALT, platelets) within normal range. In addition, the study suggests a beneficial effect of off-pump CABG when FIB-4 is elevated. This finding contradicts current randomized evidence, negating any difference between off and on-pump CABG. Since randomized trials always suffer from strong selection of low risk patients, it is conceivable that trial patients may primarily have low FIB-4 scores. Purpose To address the distribution of FIB-4 scores in a selected trial population with CAD (from the ISCHEMIA trial) and relate the degree of liver fibrosis reflected by the score to mortality. Methods The FIB-4 score was calculated for all patients. According to the standard classification, a value of greater than 1.2 reflects a 90% chance of the presence of histological liver fibrosis. The imapct of FIB-4 on late all-cause mortality was assessed as a continuous and categorical variable using maximally selected rank statistics determined FIB-4 cutoff. Cox regression model was peformed including the adjustment for the main CAD risk factors. Results Among 3735 included patients, 58.8% had a FIB-4 value above 1.2. Patients with higher FIB-4 score (cutoff= 1.64) were slighly older, presented higher prevalence of male sex, prior PCI and CABG, and prior history of atrial fibrillation and cerebrovascular disease. FIB-4 score was directly associated with higher risk of mortality when addressed as a continouos variable and as a categorical variable (Fig. 1). This relationship was evident in the overall population and in all subsets (PCI, CABG and no revascularization; Fig. 2). Conclusions The use of Fib-4 to determine the degree of liver fibrosis may be powerful to predict mortality in CAD populations which may not show any evident clinical signs of liver dysfunction. The Fib-4 distribution in this trial population, considered as selected and low risk, warrants investigating randomized trial populations having compared on- and off-pump CABG.Figure 1.Mortality: overall population.Figure 2.Mortality: by therapy subsets.

Objective Measures of Cardiometabolic Risk and Advanced Fibrosis Risk Progression in Primary Care Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

BackgroundWe examined the association of objective measures of cardiometabolic risk with progression to a high-risk for advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) at initially low- and indeterminate-risk for advanced fibrosis. MethodsWe performed a retrospective cohort study of primary care patients with MASLD between 2012 and 2021. We evaluated patients with MASLD and low- or indeterminate-risk Fibrosis-4 Index (FIB-4) scores and followed them until the outcome of a high-risk FIB-4 (≥2.67), or the end of the study period. Exposures of interest were body mass index, systolic blood pressure, hemoglobin A1c, cholesterol, estimated glomerular filtration rate, and smoking status. Variables were categorized by the threshold for primary care therapy intensification. Unadjusted and adjusted Cox regression models were developed for the outcome of time to a high-risk FIB-4 value. ResultsThe cohort included 1347 patients with a mean follow-up of 3.6 years (SD 2.7). Of the cohort, 258 (19%) had a subsequent FIB-4 > 2.67. In the fully adjusted Cox regression models, mean systolic blood pressure ≥ 150 mm Hg (1.57; 95% confidence interval (CI) 1.02-2.41) and glomerular filtration rate ≤ 59 ml/min (hazard ratio 2.78; 95%CI 2.17-3.58) were associated with an increased hazard of a high-risk FIB-4, while receiving a statin prescription (hazard ratio 0.51; 95%CI 0.39-0.66) was associated with a lower risk. ConclusionsNearly 1 in 5 primary care patients with MASLD transitioned to a high-risk FIB-4 score during 3.6 years of follow-up, and uncontrolled blood pressure and reduced kidney function were associated with an increased hazard of a FIB-4 at high-risk for advanced fibrosis.

The importance of SII and FIB-4 scores in predicting mortality in idiopathic pulmonary fibrosis patients

IntroductionQuick and simple parameters are needed to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In this way, risky patients will have the opportunity to receive early and effective treatment. In this study, we examined whether the Fibrosis-4 index (FIB-4) and systemic immune inflammation index (SII) are associated with mortality in IPF patients. Materials and methodsThe study was designed retrospectively. 100 patients diagnosed with IPF were included in the study. Variables between living patients and deceased patients were examined. ResultsOut of a total of 100 patients, 67 were divided into the surviving group and 33 into the non-surviving group. In multivariate analysis, high FIB-4 and SII values were significantly associated with an increased risk of death. ConclusionFIB-4 and SII are parameters that can predict mortality in IPF patients. In this way, IPF patients with high mortality risk will be identified earlier and more effective methods will be used in follow-up and treatment.

Unveiling the impact of psoriasis on liver health: does methotrexate play a villainous role?

Psoriasis might bring about an increased risk of liver diseases like nonalcoholic fatty liver disease and fibrosis. The impact of methotrexate on liver function is still a cause for concern, because of the studies suggesting an increased risk of liver damage and others finding no association. The focus of this study was the liver functions in psoriatic patients investigating the impact of long-term use of methotrexate on liver in psoriasis. A retrospective investigation including 140 patients with psoriasis receiving methotrexate treatment for at least 6 months and a control group consisted of 105 healthy ones was conducted. Liver function tests (AST, ALT, PLT) were assessed, and the association of baseline PASI with FIB-4 and APRI values was investigated. Additionally, FIB-4 and APRI values at baseline, 3rd, and 6th months of methotrexate treatment for psoriasis were compared. Compared with the controls, psoriatic patients exhibited significantly higher FIB-4 scores (p = 0.004). A moderate and significant correlation was observed between baseline PASI score and baseline FIB-4 score in psoriatic patients (p < 0.001, rho = 0.626). Long-term methotrexate use had no effect on APRI or FIB-4 (p = 0.104 and p = 0.475, respectively). Psoriatic patients face an elevated risk of liver fibrosis. Long-term methotrexate use does not adversely affect liver function in psoriatic patients. Noninvasive tools like APRI and FIB-4 scores can be employed to evaluate the risk of liver disease in these patients.

Human Amniotic Epithelial Cell Transplantation is Safe and Well Tolerated in Patients with Compensated Cirrhosis: A First-in-Human Trial.

Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5 × 106/kg hAEC in one IV infusion. Cohort 2 patients received 1 × 106/kg hAEC in one IV infusion. The patients in cohort 3 received 1 × 106/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy. Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).

Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase

BackgroundThe association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA.MethodsSix hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis.ResultsThe median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis.ConclusionLower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

The Inflammation-Fibrosis Combined Index: A Novel Marker for Predicting Left Ventricular Reverse Remodeling and Prognosis in Patients with HFrEF.

Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients. A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death. After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death. In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.

Exploring predictive markers for liver failure post-hepatectomy in hepatocellular carcinoma patients.

This letter to the editor addresses the study titled "Predictive value of NLR, Fib4, and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma" by Kuang et al in the World Journal of Gastrointestinal Surgery. The study acknowledges the comprehensive patient data analysis while suggesting that there is a need for further discussion on the clinical applicability of these markers across diverse patient populations. This letter recommends prospective studies for validation and considers the influence of confounding factors. This finding underscores the significance of this study in improving hepatocellular carcinoma management.

Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis.

Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Clinical features of individuals with laboratory values suggestive of advanced liver fibrosis when first treated for alcohol use disorder.

Effective screening for alcohol-associated liver disease is relevant in the context of chronic, excessive alcohol consumption. Patients with alcohol-associated liver disease are often not diagnosed until their liver disease is decompensated. We analyzed the prevalence and associations of Fibrosis-4 index (FIB-4) values suggestive of advanced liver fibrosis in patients referred for their first treatment of alcohol use disorder (AUD). We conducted a cross-sectional, multicenter study of noncirrhotic individuals referred for their first AUD treatment between March 2013 and April 2021. We obtained sociodemographic data, substance use characteristics, and blood samples at admission. We considered a FIB-4 value ≥2.67 suggestive of advanced liver fibrosis and used logistic regression analyses to identify features associated with this value. We included 604 patients (67% male), with a median age at admission of 48 years [IQR: 41-56 years]. The median duration of regular alcohol consumption was 21 years [IQR: 18-30 years] and the median alcohol consumption was 105 standard drink units (SDU)/week [IQR: 63-160 SDU/week]. A FIB-4 value ≥ 2.67 was present in 19.3% of cases. These patients reported more frequent binge drinking (75.4% vs. 66%, p = 0.05) than those with FIB-4 values below 2.67. In multivariate analysis, a history of binge drinking (OR 1.9, 95% CI, 1.05-3.47), anemia (OR 2.95, 95% CI, 1.42-6.11), leukopenia (OR 7.46, 95% CI, 2.07-26.8), and total serum bilirubin >1 mg/dL (OR 6.46, 95% CI, 3.57-11.7) were independently associated with FIB-4 values ≥2.67. One in five patients admitted to treatment for AUD without evidence of decompensated liver disease have FIB-4 values suggestive of advanced liver fibrosis. The presence of a binge drinking history, anemia, leukopenia, and elevated bilirubin levels is associated with high FIB-4 values.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.45<FIB-4<3.25; FIB-4>3.25), respectively group 1,2,3. At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.45<FIB-4<3.25 (24.1%, group 2) and 69 a FIB-4>3.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.45<FIB-4<3.25 (34.4%, group 2) and 76 a FIB-4>3.25 (42.3%, group 3). FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Diagnostic performances of Fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction-associated steatotic liver disease in Asian primary care clinics.

We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n=6740). The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n=80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p=0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p=0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

Vitamin D Deficiency Is Associated with Advanced Liver Fibrosis and Impaired Fasting Glucose in Alcohol Use Disorder.

Vitamin D deficiency is a risk factor for liver disease, insulin resistance, and beta cell dysfunction. Individuals with alcohol use disorder (AUD) have many comorbidities, with a heavy burden of liver disease and metabolic complications, including type 2 diabetes mellitus (T2DM). We aimed to analyze the prevalence and associations of vitamin D deficiency in patients admitted for in-hospital treatment of AUD. A cross-sectional study was conducted in patients consecutively admitted for the treatment of AUD between January 2017 and October 2023. Sociodemographic data, substance use characteristics, and blood parameters were available at admission. Vitamin D status was assessed through the serum concentrations of 25-hydroxyvitamin D [25(OH)D] levels using a direct competitive chemiluminescent immunoassay method. Deficiency of vitamin D was defined as a concentration less than 20 ng/mL; impaired fasting glucose (IFG) was defined by fasting blood glucose >100 mg/dL (5.6 mmol/L), and advanced liver fibrosis by an FIB-4 index >3.25. Two hundred and forty-three patients were included (75% male) with a mean age of 49 ± 10 years, mean BMI of 26.4 ± 7.3, mean alcohol consumption of 163 ± 81 g/day, and a mean duration of AUD of 18.1 ± 11.2 years. Mean 25(OH)D, fasting blood glucose, AST, ALT, and platelets were 14.4 ± 10.2 ng/mL, 103.4 ± 40.9 mg/dL, 55.1 ± 75.8 U/L, 44.8 ± 76.6 U/L, and 206.3 ± 84.8 × 109/L, respectively. The prevalence of vitamin D deficiency was 80.6%, and 41.1% of patients had levels less than 10 ng/mL. IFG was present in 32.3% of patients, and 20.5% had FIB-4 values >3.25. In the multivariable analysis, IFG (OR, 2.51; 95% CI: 1.02-6.17, p = 0.04) and advanced liver fibrosis (OR, 4.27; 95% CI: 1.21-15.0, p = 0.02) were the only factors associated with vitamin D deficiency. Vitamin D deficiency was very prevalent in this series of patients with AUD and was associated with impaired fasting glucose and advanced liver fibrosis.

Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population.

The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes. We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations. FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs. The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy

Background and AimsChronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in HBV-suppressed patients. MethodsWe conducted a case-control study involving 120 non-cirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and FIB-4-matched controls. Clinical and laboratory data at viral suppression, including BMI, comorbidities, pre-treatment HBV viral load, HBe antigen status, HCV and HIV co-infections, liver chemistries, and APRI values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. ResultsCase and control groups had similar ages (51.4±9.9 vs. 51.4±10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, p=0.01) and more diabetes prevalence (50.0% vs. 26.3%, p=0.01), while other comorbidities and laboratory parameters were comparable (p>0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46–6.13), 2.31 (1.23–4.36), 2.71 (1.05–6.99), p=0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, p=0.006), while diabetes showed borderline significance (aHR: 1.99, p=0.072). ConclusionsIn HBV-infected patients achieving viral suppression with therapy, a BMI > 23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

Predictive value of NLR, Fib4, and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma.

Neutrophil-lymphocyte ratio (NLR), fibrosis index based on four factors (Fib4), aspartate aminotransferase-to-platelet ratio index (APRI) can be used for prognostic evaluation of hepatocellular carcinoma. However, no study has established an individualized prediction model for the prognosis of hepatocellular carcinoma based on these factors. To screen the factors that affect the prognosis of hepatocellular carcinoma and establish a nomogram model that predicts postoperative liver failure after hepatic resection in patients with hepatocellular carcinoma. In total, 220 patients with hepatocellular carcinoma treated in our hospital from January 2022 to January 2023 were selected. They were divided into 154 participants in the modeling cohort, and 66 in the validation cohort. Comparative analysis of the changes in NLR, Fib4, and APRI levels in 154 patients with hepatocellular carcinoma before liver resection and at 3 mo, 6 mo, and 12 mo postoperatively was conducted. Binary logistic regression to analyze the influencing factors on the occurrence of liver failure in hepatocellular carcinoma patients, roadmap prediction modeling, and validation, patient work characteristic curves (ROCs) to evaluate the predictive efficacy of the model, calibration curves to assess the consistency, and decision curve analysis (DCA) to evaluate the model's validity were also conducted. Binary logistic regression showed that Child-Pugh grading, Surgical site, NLR, Fib4, and APRI were all risk factors for liver failure after hepatic resection in patients with hepatocellular carcinoma. The modeling cohort built a column-line graph model, and the area under the ROC curve was 0.986 [95% confidence interval (CI): 0.963-1.000]. The patients in the validation cohort utilized the column-line graph to predict the probability of survival in the validation cohort and plotted the ROC curve with an area under the curve of the model of 0.692 (95%CI: 0.548-0.837). The deviation of the actual outcome curves from the calibration curves of the column-line plots generated by the modeling and validation cohorts was small, and the DCA confirmed the validity. NLR, Fib4, and APRI independently influence posthepatectomy liver failure in patients with hepatocellular carcinoma. The column-line graph prediction model exhibited strong prognostic capability, with substantial concordance between predicted and actual events.

FIB-4 and APRI scores for progressive liver fibrosis diagnosis in children with biliary atresia.

Finding non-invasive methods to predict the degree of liver fibrosis is very important in managing children with biliary atresia. Therefore, we explored the predictive value of APRI, FIB-4, and serological markers for liver fibrosis in children with biliary atresia. This study retrospectively reviewed data from children diagnosed with BA between March and December 2022. Liver tissue pathology specimens were obtained during surgery. The serum markers were measured within 2 days before the Kasai procedure or liver transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) and the four-factor-based fibrosis index (FIB-4) were calculated. The outcome was the diagnosis of progressive liver fibrosis. This study reviewed the data from 41 children with biliary atresia. APRI had 52% sensitivity and 83% specificity for progressive liver fibrosis, while FIB-4 had 83% sensitivity and 67% specificity. Their areas under the curve were not significantly different from those of conventional markers. Although they were not better than conventional markers, APRI and FIB-4 can be used as follow-up markers for progressive liver fibrosis in patients with biliary atresia, but their predictive value was moderate. Additional studies are necessary to determine whether they could be combined with other markers to improve their predictive value.

Seroprevalence of hepatitis E virus in patients with chronic liver disease.

The seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to cirrhosis. To estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic data and risk factors, as well as clinical-laboratory and ultrasound parameters. Cross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and, in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out. Investigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17 with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age of 57 ± 13years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative. Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema, lower platelet count, higher APRI and FIB-4 values, and splenomegaly. Although the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced chronic liver disease.

Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: a nationwide real-world U.S. study.

A substantial proportion of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) do not have cirrhosis. Data regarding the incidence and predictors of HCC development in NAFLD without cirrhosis are limited. We conducted a large, national study of NAFLD patients without documented cirrhosis to examine the incidence and predictors for HCC development. This retrospective study included 751,603 NAFLD patients (54% female) without documented cirrhosis derived from the deidentified Optum Clinformatics® Data Mart Database. Patients with cirrhosis, platelets < 120,000/µL or FIB-4 values > 2.67 were excluded. The mean age was 53.7 ± 15.0years, 45.9% were male, 39.5% had diabetes, 57.6% were White, 18.4% Hispanic, 8.2% Black and 4.9% were Asian. The mean platelet count was 264,000 ± 72,000/µL, and 96.3% of patients had a FIB-4 < 1.30. Over 1,686,607 person-years of follow-up, there were 76 incident cases of HCC, resulting in an HCC incidence rate of 0.05 per 1000 person-years. There was a higher HCC incidence rate among patients with platelets ≤ 150,000/µL, versus those with platelets > 150,000/µL (0.23 per 1000 person-years, vs. 0.04 per 1000 person-years, p = 0.02) but not in subgroup analyses for age, sex, race/ethnicity or diabetes. Using multivariable Cox proportional hazards model adjusted multiple confounders, platelet count ≤ 150,000/µL remained an independent predictor of HCC development (adjusted HR 5.80, 95% CI 1.67-20.1, p = 0.006). HCC incidence in NAFLD without documented cirrhosis was below the threshold for cost-effective HCC surveillance in overall and multiple subgroup analyses. Platelet count < 150,000/µL may be a useful predictor of HCC development in this population.

Routinely Calculable Biomarkers Are Associated with the Development of Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation

Introduction: Sinusoidal obstruction syndrome (SOS) is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). As the immediate initiation of SOS treatment has been shown to be associated with a better prognosis, SOS prediction is clinically important. Biomarkers composed of some routine parameters, such as the aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), and albumin-bilirubin (ALBI), have been widely used to evaluate various hepatic diseases. However, the contribution of these hepatic biomarkers to the prediction and diagnosis of SOS has not been estimated yet. Here, we investigated whether routinely calculable biomarkers, endothelial activation and stress index (EASIX), APRI, FIB-4, ALBI, model for end-stage liver disease (MELD), and MELDNa were associated with the development of SOS. Patients and Methods: A total of 141 patients (corresponding to 161 transplant cases) who underwent allogeneic HSCT at our institution between January 2012 and December 2022 were retrospectively analyzed. The median age at transplantation was 52 years (range: 19-69). The primary diseases included AML (n = 59), ALL/LBL (n = 34), MDS (n = 20), malignant lymphoma (n = 15), plasma cell neoplasm (n = 4), CML/MPN (n = 10), bone marrow failure (n = 3), and others (n = 16). The graft sources were from 30 related and 131 unrelated donors. The numbers of bone marrow, peripheral blood, and cord blood sources were 65, 29, and 67, respectively. Conditioning consisted of myeloablative (n = 68) and reduced-intensity (n = 93) regimens. Haplo-identical transplantation was not performed in this cohort. SOS was diagnosed according to the European Society for Blood and Marrow Transplantation diagnostic criteria 2023. The baseline value of each biomarker before conditioning was compared between the SOS-developing and non-SOS groups, using the Kruskal-Wallis test and a post-hoc test with the Bonferroni method. To evaluate the contribution of biomarkers on SOS diagnosis, we configured matched paired controls from non-SOS cases (three non-SOS controls per SOS case), adjusting for age, sex, last follow-up day, HLA mismatch, and hematopoietic cell transplantation-specific comorbidity index. The values of biomarkers in the SOS and matched paired control groups were compared using the Mann-Whitney U test. In the present study, the negative sign of ALBI was reversed for convenience in analysis. Results and Discussion: Twenty cases were diagnosed to have developed clinical SOS (10 classical SOS and 10 late onset SOS cases). All biomarkers at baseline were significantly different for classical SOS versus non-SOS cases. The median values of EASIX, APRI, FIB-4, ALBI, MELD, and MELDNa were 8.70 vs 1.09 (range: 0.57-24.68 vs 0.22-34.10, P &amp;lt; 0.001), 4.97 vs 0.60 (range: 0.33-32.07 vs 0.11-10.30, P &amp;lt; 0.001), 10.80 vs 1.84 (range: 1.37-38.01 vs 0.31-44.69, P &amp;lt; 0.001), 1.84 vs 2.43 (range: 0.83-3.71 vs 1.33-3.27, P = 0.012), 8.0 vs 7.0 (range: 6-12 vs 6-17, P = 0.028), and 9.5 vs 7.0 (range: 6-18 vs 6-17, P = 0.025), respectively. Moreover, among SOS cases, biomarkers at SOS diagnosis were significantly different compared with those of matched paired controls. The median values were 33.67 vs 3.90 (range: 4.54-252.18 vs 0.28-87.22, P &amp;lt; 0.001), 9.90 vs 1.79 (range: 3.33-127.33 vs 0.19-23.94, P &amp;lt; 0.001), 43.00 vs 6.80 (range: 7.91-182.27 vs 0.60-54.92, P &amp;lt; 0.001), 1.06 vs 2.02 (range: 0.37-1.88 vs 0.52-3.19, P &amp;lt; 0.001), 14.0 vs 7.0 (range: 10-30 vs 6-23, P &amp;lt; 0.001), and 16.5 vs 8.5 (range: 10-31 vs 6-29, P &amp;lt; 0.001), respectively. These results indicate that these biomarkers are associated with SOS, as well as support its diagnosis. As these biomarkers were concise, rapidly calculable, and dispensable with special techniques, their use might be clinically superior to other tests. Conclusion: These routinely calculable biomarkers are associated with the development of SOS. Furthermore, these biomarkers are clinically useful for diagnosis of SOS. Further studies are required to improve the performance and discover an optimal biomarker.