Non-invasive Markers Of Hepatic Fibrosis Research Articles

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis

BackgroundResmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. MethodsElectronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. ResultsThree randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD −27.76% [95%CI: −32.84, −22.69]; for resmetirom 100 mg: MD −36.01% [95%CI: −41.54, −30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD −21.45 dBm [95%CI: −29.37, −13.52]; for resmetirom 100 mg: MD −25.51 dBm [95%CI: −33.53, −17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. ConclusionResmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.

Noninvasive markers of hepatic fibrosis and their clinical application in coronary artery disease.

Noninvasive markers of hepatic fibrosis and their clinical application in coronary artery disease.

1276. Noninvasive Assessment of Change in Hepatic Fibrosis Following Initiation of Integrase Inhibitors in Women Living with HIV

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in persons with HIV and can lead to hepatic fibrosis. Integrase strand-transfer inhibitors (INSTIs), first-line agents in antiretroviral therapy (ART), are associated with increased body mass index (BMI), particularly in women living with HIV (WLWH). We evaluated change in hepatic fibrosis risk following INSTI initiation in WLWH. Table 1.Change over time in hepatic fibrosis scores among group switching to INSTI-regimens versus group staying on non-INSTI regimens INSTI=integrase strand-transfer inhibitor; SD=standard deviation; FIB-4=Fibrosis-4 Score (calculated by Age*AST/[platelet count*ALT1/2]; APRI=AST to Platelet Ratio Index (calculated by [AST/AST upper limit of normal]/platelet count); NFS = Non Alcoholic Fatty Liver Disease Fibrosis Score (calculated by -1.675+(0.037*age) + (0.094*body mass index)+(1.13*hyperglycemia or diabetes [yes=1, no=0])+ (0.99*AST/ALT)-(0.013*platelet count)-(0.66*albumin)); CI=Confidence Interval. Linear regression model with unstructured covariance matrix for repeated observations with a person. Adjusted models for all outcomes included the following covariates: age, race/ethnicity, education, baseline CD4 lymphocyte count, baseline antiretroviral anchor drug, and abacavir, tenofovir disoproxil fumarate, and tenofovir alafenamide use. Body mass index was included in models for FIB-4 and APRI only. Age was included for APRI only. Methods Data from 2007-2020 were analyzed from virologically-suppressed WLWH enrolled in the Women’s Interagency HIV Study (WIHS). We excluded WLWH with untreated viral hepatitis, heavy alcohol use and autoimmune or metabolic chronic liver disease. WLWH who switched to or added an INSTI to ART were compared to women who remained on non-INSTI ART. Outcomes included change in noninvasive markers of hepatic fibrosis: Fibrosis-4 (FIB4), AST to Platelet Ratio Index (APRI), and NAFLD fibrosis score (NFS), measured 4-12 months before and 4-19 months post INSTI switch/add. Longitudinal linear regression models compared change over time in each outcome by group, adjusted for covariates. Results 872 WIHS participants (323 INSTI, 549 non-INSTI) were followed for a median 3.0 years (Q1 2.0, Q3 4.5). Mean age was 47.2 years (SD 9.0), 61% were Non-Hispanic Black, and mean BMI was 31.4 (8.8) kg/m2. Absolute mean changes in FIB4, APRI, and NFS scores were +0.021, -0.005, +0.194, respectively, in the INSTI group compared to +0.003, -0.011, +0.016, respectively, in the non-INSTI group (Table 1). No significant differences in mean AST and ALT change between the INSTI and non-INSTI groups were noted. There was a significant increase in NFS score in the INSTI group (p&amp;lt; 0.0001) and this difference remained in adjusted models (p=0.0135). Compared to the non-INSTI group, a larger proportion of participants in the INSTI group changed to a higher NFS risk category: 15.7% vs 9.0%, p=0.014. Conclusion Starting INSTIs was associated with minimal change in FIB4 and APRI scores but increased NFS score in WLWH. The increase in NFS score likely reflects BMI gain with INSTI use, as BMI is not factored into FIB4 or APRI calculators and AST and ALT did not change significantly. Nonetheless, patients starting INSTIs need close monitoring of metabolic changes and low thresholds for additional noninvasive liver fibrosis testing. Disclosures Michael A. Yu, MD, Ligera: Advisor/Consultant Maria L L. Alcaide, MD, Gilead: Advisor/Consultant Adaora A. Adimora, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support Jennifer C. Price, MD, PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support Phyllis C. Tien, MD, MSc, Gilead: Grant/Research Support|Merck: Grant/Research Support Cecile D. Lahiri, MD, MS, Theratechnologies: Advisor/Consultant.

Antioxidants-based scores to predict Hepatocellular Carcinoma Patients among Chronic Hepatitis C individuals: correlation with Non-invasive Markers of Hepatic Fibrosis

Antioxidants-based scores to predict Hepatocellular Carcinoma Patients among Chronic Hepatitis C individuals: correlation with Non-invasive Markers of Hepatic Fibrosis

The relation of 25-hydroxy vitamin D concentrations to liver histopathology, seasonality and baseline characteristics in chronic hepatitis C virus genotype 2 or 3 infection.

Background and objectivesThe hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy.Method25(OH)D was measured post-hoc in pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated.ResultsMean 25(OH)D concentration was 59 ±23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p ≤0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity.ConclusionFibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.

Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone

IntroductionAt least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is...

The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients.

Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.

Ultrasonographic Evaluation of Fatty Pancreas in Serbian Patients with Non Alcoholic Fatty Liver Disease-A Cross Sectional Study.

Background and Objectives: The aim of the study was to determine the association between presences of fatty pancreas (FP) with the features of metabolic syndrome (MeS) in patients with non–alcoholic fatty liver disease (NAFLD) and to establish a new noninvasive scoring system for the prediction of FP in patients with NAFLD. Material and Methods: 143 patients with NAFLD were classified according to FP severity grade into the two groups and evaluated for diagnostic criteria of MeS. All patients underwent sonographic examination with adiposity measurements and the liver biopsy. Liver fibrosis was evaluated semi-quantitatively according to the METAVIR scoring system and using non-invasive markers of hepatic fibrosis. Results: Waist circumference (WC) was predictive for increased risk of FP in NAFLD patients. Elevated fasting plasma glucose, total cholesterol, serum amylase and lipase levels were associated with presence of severe FP (p value = 0.052, p value = 0.007, p value = 0.014; p value = 0.024, respectively). Presence of increased amounts of mesenteric fat was associated with severe FP (p value = 0.013). The results of this study demonstrated highly significant association between NAFLD and presence of FP. The model for predicting the presence of FP was designed with probability value above 6.5. Conclusion: Pancreatic fat accumulation leads to worsening of pancreatic function which in turns exacerbates severity of metabolic syndrome associated with both, NAFLD and NAFPD.

Significance of biglycan and osteopontin as non-invasive markers of liver fibrosis in patients with chronic hepatitis B virus and chronic hepatitis C virus

Several studies were performed to evaluate the degree of liver fibrosis by non-invasive markers. We aimed to assess the diagnostic value of both biglycan (BGN) and osteopontin (OPN) as non-invasive...

Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis.

Hepatic venous pressure gradient (HVPG) is the best recommended tool to measure portal pressure, but is invasive. HVPG helps in prognosticating cirrhosis and predictits complications. Aminotransferase to platelet ratio index (APRI) is a simple non-invasive marker of hepatic fibrosis. We aimed to correlate APRI with HVPG and to determine the usefulness of APRI in predicting complication of cirrhosis. APRI and HVPG were measured in consecutive patients of cirrhosis aged 18 to 70 years. Spearman's rho was used to estimate their correlation; acut-off valueof APRI topredict severe portal hypertension (HVPG > 12mmHg) was determined. This study, conducted between August 2011 and December 2014, included 277 patients, median age 51 (range: 16-90) years, 84% males. Etiology of cirrhosis was alcohol in 135 (49%), cryptogenic/nonalcoholic steatohepatitis (NASH) in 104 (38%), viral in 34 (12%), and others in 4 (1%). Median Child-Turcott-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 (5-11) and 11 (6-33), respectively. Median HVPG was 17.0 (1.5-33) mmHg and median APRI was 1.09 (0.21-12.22). There was positive correlation between APRI andHVPG (Spearman's rho 0.450, p < 0.001). The area under the receiver operating characteristic (ROC) curve of APRI for predicting severe portal hypertension was 0.763 (p < 0.01). Youden's index defined the cut-off of APRI for predicting HVPG > 12mmHg was 0.876 with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 71%, 78%, 94%, 38%, and 73%, respectively. APRI also correlated well with CTP, variceal size, bleeding status, ascites but not with MELD. APRI score of 0.876 has an acceptable accuracy topredictsevere portal hypertension (HVPG > 12mmHg). High APRI also correlated with severity of cirrhosis and its complications. Thus, APRI may be used as a simple, bedside, non-invasive, and inexpensive tool for evaluating portal hypertension and complications of cirrhosis.

Serum hyaluronic acid as a noninvasive marker of hepatic fibrosis in chronic hepatitis c patients

Background Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic with few clinical signs of liver disease. Recognition of the presence of fibrosis or cirrhosis is difficult without liver biopsy, but with the availability of effective treatments, such as interferon, and the potential for progression to hepatoma in some cases, an accurate measure of the stage of disease is important. Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis or cirrhosis. Aim of the work The aim of this study was to evaluate the serum level of HA as a noninvasive marker of hepatic fibrosis in comparison with liver biopsy and indirect serum fibrosis markers such as AST/ALT ratio and aspartate transaminase to platelet ratio index (APRI) in chronic HCV patients. Patients and methods Our patients were classified into three groups: group 1 included 20 patients with mild hepatic fibrosis (F1 stage); group 2 included 20 patients with moderate hepatic fibrosis (F2 stage); and group 3 included 20 patients with marked hepatic fibrosis and cirrhosis (F3 and F4 stages). The control group included 20 normal volunteers. Serum HA level evaluation, liver function tests, and complete blood count were carried out for all groups, whereas liver biopsy was performed only for patients to determine the stage of liver fibrosis. Results There was a highly significant increase in serum HA level in group 2 and group 3 in comparison with the control group and a significant increase in group 1 in comparison with the control group. However, there was highly significant increase in group 3 in comparison with group 1 and group 2 and a significant increase in group 2 in comparison with group 1. The cutoff point for HA level was greater than 42.18 ng/l to discriminate between the patient and the control group, with a sensitivity of 91.7% and a specificity of 95.0% for HA. The cutoff point for HA level was greater than 81.68 ng/l to discriminate between group 1 (mild fibrosis) and group 2 (moderate fibrosis), with a sensitivity of 100% and a specificity of 70%. The cutoff point for HA level to discriminate between group 2 (moderate fibrosis) and group 3 (severe fibrosis and cirrhosis) was greater than 167.98 ng/l, with a sensitivity of 90% and specificity of 80%. There was a significant positive correlation between serum HA level and APRI. Conclusion HA is a promising reliable simple noninvasive marker for assessing liver fibrosis in HCV-infected patients with high sensitivity and specificity. There was a positive correlation between serum HA level with stages of hepatic fibrosis and APRI.

Assessment of Serum Hydroxyproline and Osteopontin as Noninvasive Markers of Hepatic Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection is a progressive disease that may result in chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Liver fibrosis is an essential factor that must be considered in the management of patients with HCV. Although liver biopsy represents the gold standard for evaluating the presence, type and stage of liver fibrosis, this technique remains a costly and invasive procedure. Therefore, several diagnostic methods for determining liver fibrosis, such as the detection of serum biomarkers, have been used. Objective: To evaluate the use of serum hydroxyproline (HYP) and osteopontin (OPN) as non invasive direct markers to assess the degree of hepatic fibrosis in Egyptian patients with chronic HCV infection in comparison to indirect markers such as aspartate aminotransferase platelet ratio index (APRI) and to determine the most diagnostically accurate non invasive marker of hepatic fibrosis, hoping to replace liver biopsy in the next few years. Methodology: This study was carried out on 48 patients with chronic HCV infection who had undergone liver biopsy and scored as mild fibrosis (F1), moderate fibrosis (F2), sever fibrosis (F3) and liver cirrhosis (F4) based on Metavir scoring system, and 12 age and sex matched controls. The serum levels of HYP and OPN were measured by enzyme linked immunosorbent assay (ELISA). Results: There was a highly significant increase in HYP, OPN and APRI in all patients groups in comparison to control group and their increase was significantly associated with the degree of hepatic fibrosis. Furthermore, HYP, OPN and APRI values showed highly significant increase in significant hepatic fibrosis (F2- F4) in comparison to mild fibrosis (F1), and in hepatic cirrhosis (F4) in comparison to hepatic fibrosis (F1-F3). There was a highly significant positive correlation between serum HYP level, OPN and APRI. The receiver operating characteristic (ROC) curve analysis revealed that OPN has the highest area under the curve (AUC) value for discriminating fibrosis stages, followed by HYP and lastly APRI. Conclusion: This study demonstrated that OPN was the most diagnostically accurate marker for assessing the severity of hepatic fibrosis and served as a prognostic index towards the progression of hepatic fibrosis to cirrhosis in patients with chronic HCV infection, followed by HYP and lastly APRI. These findings indicated that OPN and HYP could be used as non invasive markers of hepatic fibrosis and cirrhosis which would help to reduce the need for liver biopsy in chronic HCV infection

Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors

BackgroundMetabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined.MethodsUntargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software.ResultsA 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-α and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction.ConclusionsLipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients.

732 ENHANCED LIVER FIBROSIS (ELF) SCORE IS RELATED TO LIVER DYSFUNCTION AND PREDICTS MORTALITY IN CIRRHOSIS

Background: The Enhanced liver fibrosis (ELF) test is a noninvasive fibrosis panel composed of hyaluronic acid (HA), procollagen-3 N-terminal peptide (P3NP), and tissue inhibitor of metalloproteinase-1 (TIMP1). Previous studies have established high diagnostic accuracy of the ELF score to assess hepatic fibrosis and to predict liver-related clinical outcomes in chronic viral hepatitis and fatty liver disease. Aim of the present study was to relate baseline ELF scores to mortality in a cohort of cirrhotic patients. Methods: We enrolled 63 consecutive cirrhotic patients admitted to our outpatient liver clinic (29% females; age: 58±10 years; etiology alcohol in 64%). Serum samples obtained at baseline were used to perform ELF test (Siemens Health Care, Vienna, Austria). The prognostic value of ELF score, Child–Pugh (CP) score and model for end-stage liver disease (MELD) obtained at baseline was assessed by receiver operating characteristic (ROC) analysis. Logistic regression analysis with backward elimination of variables was used to determine independent prognostic variables. Results: Baseline characteristics of our study cohort were: CP-A 38%, CP-B 43%, CP-C 19%, CPS 7 (6, 9), MELD 13 (10, 16). ELF score increased progressively with the stage of cirrhosis as estimated by CP stage (CP-A: 10.8±1.0; CP-B: 12.2±1.0; CP-C: 13.2±1.3). During a median follow-up of 43 months, 27 patients developed hepatic decompensation, 18 patients died and 5 patients unterwent liver transplantation (LT). ROC analysis of baseline variables revealed superior diagnostic accuracy of ELF score compared to CP score and MELD for prediction of a combined endpoint death/LT at 1 year (AUC: ELF 0.80, CP score 0.71, MELD 0.71). On logistic regression analysis, ELF score remained the only significant prognostic variable for the combined endpoint death/LT at 1 year. Conclusion: Our results suggest that ELF score, a noninvasive marker of hepatic fibrosis, is related to severity of liver dysfunction and to mortality in cirrhosis and may represent a novel prognostic marker in chronic liver failure.

733 NEOEPITOPES DERIVED FROM EXTRACELLULAR MATRIX DEGRADATION REFLECT LIVER FUNCTION, FIBROSIS AND HVPG IN HIV-PATIENTS

Background: The Enhanced liver fibrosis (ELF) test is a noninvasive fibrosis panel composed of hyaluronic acid (HA), procollagen-3 N-terminal peptide (P3NP), and tissue inhibitor of metalloproteinase-1 (TIMP1). Previous studies have established high diagnostic accuracy of the ELF score to assess hepatic fibrosis and to predict liver-related clinical outcomes in chronic viral hepatitis and fatty liver disease. Aim of the present study was to relate baseline ELF scores to mortality in a cohort of cirrhotic patients. Methods: We enrolled 63 consecutive cirrhotic patients admitted to our outpatient liver clinic (29% females; age: 58±10 years; etiology alcohol in 64%). Serum samples obtained at baseline were used to perform ELF test (Siemens Health Care, Vienna, Austria). The prognostic value of ELF score, Child–Pugh (CP) score and model for end-stage liver disease (MELD) obtained at baseline was assessed by receiver operating characteristic (ROC) analysis. Logistic regression analysis with backward elimination of variables was used to determine independent prognostic variables. Results: Baseline characteristics of our study cohort were: CP-A 38%, CP-B 43%, CP-C 19%, CPS 7 (6, 9), MELD 13 (10, 16). ELF score increased progressively with the stage of cirrhosis as estimated by CP stage (CP-A: 10.8±1.0; CP-B: 12.2±1.0; CP-C: 13.2±1.3). During a median follow-up of 43 months, 27 patients developed hepatic decompensation, 18 patients died and 5 patients unterwent liver transplantation (LT). ROC analysis of baseline variables revealed superior diagnostic accuracy of ELF score compared to CP score and MELD for prediction of a combined endpoint death/LT at 1 year (AUC: ELF 0.80, CP score 0.71, MELD 0.71). On logistic regression analysis, ELF score remained the only significant prognostic variable for the combined endpoint death/LT at 1 year. Conclusion: Our results suggest that ELF score, a noninvasive marker of hepatic fibrosis, is related to severity of liver dysfunction and to mortality in cirrhosis and may represent a novel prognostic marker in chronic liver failure.

The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients

Background. Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. Methods. The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Lok's model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. Results. Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Lok's model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. Conclusions. Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.

Acoustic radiation force impulse imaging as noninvasive marker of hepatic fibrosis

Background: Acoustic Radiation Force impulse Imaging (ARFI) is a novel non-invasive technique studying the localized mechanical properties of tissue by utilizing short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response(tissue displacement), providing a measure of tissue elasticity. Aims: To investigate the feasibility of ARFI imaging as a noninvasive method for assessing liver fibrosis compared to liver biopsy scores in patients with suspected chronic liver disease. Method: A prospective comparison study of ARFI elastography (Virtual Touch imaging, ACUSON S2000 ultrasound unit, Siemens) in a consecutive series of patients who underwent liver biopsy for assessment of liver stiffness was measured in meters per second. Mean ARFI velocities were compared with Modified Ishak scores and Brunt score for fibrosis in liver biopsy findings. Results: Study included 40 patients of suspected chronic liver disease who underwent liver biopsy and ARFI Elastography from the same segment of liver between the age group of 38.7 ± 14.4 years with predominant male gender (80%) over a period of 1 year. Cryptogenic cause for chronic hepatitis (32.5%) was the leading cause followed by NASH (22.5%) and then contributed equally by viral etiology of HCV and HBV (20%) each. The median ARFI value is 1.55mt/sec and there is an increasing trend of ARFI values as Childs score increases. ARFI proved to be a better predictor of advanced fibrosis (F3 or F4). The spearman rho correlation coefficients between median values of ARFI measurements and the histological fibrosis stage of the Metavir score and Brunt score were both highly significant (P< 0.01) with rho of 0.523 and 0.69 respectively. Conclusion: Our study showed that ARFI sonoelastography stands out on account of its very good correlation with liver biopsy (gold standard for evaluating liver fibrosis).

Predictors of Accuracy of Non-Invasive Markers of Hepatic Fibrosis

Predictors of Accuracy of Non-Invasive Markers of Hepatic Fibrosis

Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population

BackgroundA reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD.MethodsThe areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (109/L) × √ALT (IU/L))ResultsAdvanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies.ConclusionThe FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.

The combination of endoglin and FIB-4 increases the accuracy of detection of hepatic fibrosis in chronic hepatitis C patients

Background and aim: In patients infected with chronic hepatitis C virus, liver biopsy is the gold standard method of staging fibrosis. Different combinations of serum markers attempted to correlate with hepatic fibrosis in place of liver biopsy and have shown encouraging results. The aim of our study is to evaluate the diagnostic value of endoglin and FIB-4 as non-invasive markers of hepatic fibrosis in HCV patients. Methods: We estimated serum endoglin & FIB-4 index in 40 infected chronic hepatitis C patients. Histological staging of hepatic fibrosis was done according to the METAVIR scoring system. Results: Both endoglin and FIB-4 index showed positive correlation with age and aspartate transaminase and inverse correlation with albumin. The diagnostic performance determined by AUROCs for early fibrosis (≤F2), was 0.868 for endoglin and 0.887 for FIB-4, at cut off va- lues of 5.5 & 0.98 with sensitivity of 64.3% & 82.1%, and specificity of 100% & 85% respectively. For ad-vanced fibrosis (>F2), the AUROC was 0.98 for endoglin and 0.967 for FIB-4, obtained at cut off values of 6.29 & 1.6, with sensitivity of 100% & 91.7%, and specificity of 89.3% & 92.9%, respectively. Conclusion: Both serum endoglin and FIB-4 index are fairly accurate in differentiating stages of hepatic fibrosis; their combination in a single equation enhanced the accuracy of fibrosis detection in chronic HCV patients.