Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion dependent beta thalassaemia: a cross sectional study

Objective To evaluated the performance of FIB-4 score as a screening tool to detect significant liver fibrosis (F2) compared to transient elastography (TE) among chronic transfusion-dependent beta-thalassemia (TDT) patients, in a resource-poor setting. Design A cross-sectional study Setting Adolescent and Adult Thalassaemia Care Center (University Medical Unit) Kiribathgoda Sri Lanka. Participants 45 TDT patients who have undergone more than 100 blood transfusions with elevated serum ferritin more than 2000ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibody were excluded. Outcome measures TE and FIB-4 score were estimated at the time of recruitment in all participants. Pre-defined cut-off values for F2 extracted from previous studies for TE and FIB-4 score were compared. A new cut-off value for FIB-4 score was estimated using ROC curve analysis to improve the sensitivity for F2 prediction. Results Of the selected 45 TDT patients 22(49%) were males. FIB-4 score showed a significant linear correlation with TE (r= 0.52 p< 0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4 we improved the pick-up rate of F2 to 72%. Conclusions Regardless of the cut-off point FIB-4 score cannot be used as a good screening tool to pick-up F2 in patients with TDT irrespective of their splenectomy status. On the contrary at 1.3 cut off value though FIB-4 is a very poor detector for F2 fibrosis it will not erroneously diagnose F2 fibrosis in those who do not have it.

Liver Steatosis: Better Predictor of CKD in MAFLD Than Liver Fibrosis as Determined by Transient Elastography With Controlled Attenuation Parameter

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP).Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold.Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values &gt;353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values &gt;353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values.Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.

Magnetic Resonance Imaging-Proton Density Fat Fraction vs. Transient Elastography-Controlled Attenuation Parameter in Diagnosing Non-alcoholic Fatty Liver Disease in Children and Adolescents: A Meta-Analysis of Diagnostic Accuracy

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents, and its prevalence increases with obesity. Magnetic resonance imaging (MRI) and transient elastography (TE) have been widely used to non-invasively evaluate NAFLD in adults. This study aimed to determine the efficacy and accuracy of MRI-proton density fat fraction (MRI-PDFF) and TE-controlled attenuation parameter (TE-CAP) in distinguishing hepatic steatosis in children and adolescents.Materials and Methods: In this meta-analysis, the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases were searched for articles that reported studies on the accuracy of MRI-PDFF or TE-CAP in grading the steatosis in children and adolescents with NAFLD. This study compared the sensitivity, specificity, and hierarchical summary receiver operating characteristic curves (HSROCs) of MRI-PDFF and TE-CAP in distinguishing between steatosis grades S0 and S1–3.Results: A total of eight articles involving 874 children and adolescents with NAFLD were included in this study. The proportions of steatosis grades were 5 and 95% for S0 and S1–3, respectively. MRI-PDFF accurately diagnosed S1–3 steatosis, with a summary sensitivity of 0.95 (95% CI, 0.92–0.97), specificity of 0.92 (95% CI, 0.77–0.98), and HSROC of 0.96 (95% CI, 0.94–0.98). Likewise, TE-CAP accurately diagnosed S1–3 steatosis, with a summary sensitivity of 0.86 (95% CI, 0.70–0.94), specificity of 0.88 (95% CI, 0.71–0.96), and HSROC of 0.94 (95% CI, 0.91–0.95). Following a “positive” measurement (over the threshold value) for S1–3, the corresponding post-test probabilities of MRI-PDFF and TE-CAP for the presence of steatosis reached 92 and 88%, respectively, at the pretest probability of 50%. When the values were below the mentioned threshold values (“negative” results), the post-test probabilities of MRI-PDFF and TE-CAP became 5 and 13%, respectively.Conclusion: Both MRI-PDFF and TE-CAP are highly accurate non-invasive methods to grade the hepatic steatosis in children and adolescents with NAFLD. Furthermore, MRI-PDFF is significantly more accurate in assessing steatosis grade than TE-CAP.Systematic Review Registration: PROSPERO, identifier: CRD42021220422.

Metabolic associated fatty liver disease is highly prevalent in the post-acute COVID syndrome

Background Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (p&lt;0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

Liver Stiffness, Albuminuria and Chronic Kidney Disease in Patients with NAFLD: A Systematic Review and Meta-Analysis

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN.Clinical trials registration: ClinicalTrials.gov (NCT02865369).

Liver Fibrosis and Steatosis in Virally Suppressed HIV-Infected Patients with Cytomegalovirus Seropositivity

Background: Cytomegalovirus (CMV) is a human herpesvirus common in people with human immunodeficiency virus (HIV). In a patient with immunocompetence, long periodic asymptomatic CMV might affect to develop the abnormal liver function and contribute to non-AIDS defining morbidity, including chronic liver disease. This study aims to know the prevalence of liver fibrosis and steatosis in virally suppressed HIV infected patients with CMV reactive and summarize the correlation of clinical presentation with liver fibrosis and steatosis in these subjects.Method: A cross-sectional study in HIV Integrated Care Unit, Cipto Mangunkusumo Hospital, was conducted from April 2019 until June 2020. Subjects enrolled in this study were suppressed HIV patients aged between 30-40 years with positive IgG CMV and already using stable ART for at least one year. Transient elastography measured the liver stiffness. Patients with liver stiffness above 7 kPa were defined as having significant liver fibrosis. In addition, Spearman correlation was conducted to evaluate the correlation of clinical presentation of subjects related to liver fibrosis and steatosis. Results: A total of subjects was included in this study. Dominantly male (62.5%) with average age 38 ± 4.68 years. The median amount of CMV DNA was 466 (17-21284) copy/ml. Significant Fibrosis was found in 17/80 (21%) subjects. In this study, clinical parameters correlated with liver fibrosis were insulin, glucose fasting, Homa IR, triglyceride, HDL, and platelet. A medium positive correlation was found in insulin, and Homa IR, with coefficient correlation for insulin, was r = 0.475, p 0.001; and coefficient correlation for Homa IR was r = 0 .487, p 0.001.Conclusion: The prevalence of liver fibrosis was 12% in these subjects. In addition, insulin and Homa IR had a positive correlation with increasing liver fibrosis.

Prevalence of Elevated Liver Stiffness Among Potential Candidates for Bariatric Surgery in the United States

Purpose Obesity represents a well-known risk factor for metabolic-dysfunction associated fatty liver disease (MAFLD) and its progression towards cirrhosis. The aim of this study is to estimate the proportion of potential candidates to a bariatric surgery intervention that has an elevated liver stiffness on vibration-controlled transient elastography (VCTE). Materials and Methods This is a cross-sectional study performed using data obtained during the 2017–2018 cycle of the National Health and Nutrition Examination Survey. Potential candidates for a bariatric surgery intervention from the general US population were identified by applying criteria from international guidelines. All included participants were evaluated by VCTE. A controlled attenuation parameter (CAP) value ≥ 288 dB/m was considered indicative of steatosis while liver stiffness measurement (LSM) was considered elevated if ≥ 9.7 kPa. Multivariable logistic regression models were fitted to identify independent predictors of both outcomes. Results A total of 434 participants were included (mean age 42.9 ± 0.6 years; 54.4% women). Among them, 76.7% (95% CI 71.7–81.0) had steatosis, while 23.1% (95% CI 17.8–29.3) had an elevated LSM. Male sex, older age, γ-glutamyltranspeptidase levels, and body mass index (BMI) were independent predictors of steatosis, while BMI was the only independent predictor of elevated LSM. Non-Hispanic black participants were protected from both outcomes, while other ethnicities were not. Conclusion The prevalence of elevated LSM is high in potential candidates for a bariatric surgery intervention. Accurate screening for occult advanced liver disease might be indicated in this patient population. Graphical abstract