Detection Of Advanced Fibrosis Research Articles

The grade of obesity affects the noninvasive diagnosis of advanced fibrosis in individuals with MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity. We aimed to assess the impact of obesity on the performance of different noninvasive tests, including liver stiffness measurement (LSM) and Agile3+ (A3+), to detect advanced fibrosis (AF) in a population of patients with MASLD encompassing a wide range of BMI values. A total of 479 patients with MASLD were consecutively included (Lyon Hepatology Institute). Clinical data and noninvasive tests, including FibroTest, LSM, A3+, Fibrosis-4 (FIB-4), magnetic resonance elastography, and liver biopsies, were collected. AF was determined by a composite endpoint, i.e., histological stage ≥ F3, overt diagnosis of cirrhosis by magnetic resonance elastography, or concordant LSM ≥ 9.6 kPa and FibroTest ≥ F3. The median BMI was 35.0 kg/m2, and the prevalence of AF was 28.6%. Patients with BMI ≥ 35 versus <35 had a lower proportion of AF, i.e., 19.3% versus 38.1% (p < 0.001), but higher indeterminate status for AF (34.2% vs. 15.4%; p < 0.001). In the case of BMI ≥ 35, LSM had lower specificity to rule in AF (77.9%) versus A3+ (90.4%), but A3+ had decreased sensitivity to rule out AF. A sequential LSM/A3+ strategy achieved high specificity to rule in AF and lowered the proportion of indeterminate cases in patients with BMI ≥ 35. The grade of obesity affects the detection of MASLD-related AF. A sequential use of LSM/A3+ could improve AF detection in patients with BMI ≥ 35.

Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis.

Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear. To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis. A cross-sectional study was conducted on individuals aged 25-75years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight. A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups. TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status.

Noninvasive Methods for Detecting Advanced Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis B: A Single-Center Retrospective Study.

The performance of noninvasive assessments to rule-in or rule-out fibrosis may improve when combined. We aimed to evaluate the efficiencies of sequential algorithms based on the aspartate aminotransferase-to-platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and transient elastography (TE) for the assessment of advanced fibrosis (AF) and cirrhosis. This study enrolled 179 CHB subjects who underwent liver biopsy (LB) before antiviral treatment. AF and cirrhosis were identified in 71 (39.7%) and 28 (15.7%) patients, respectively. Compared with TE alone, sequential FIB-4-TE and APRI-TE algorithms saved a slightly higher number of liver biopsies for the identification of advanced fibrosis (69.3% or 68.2% vs 63.7%, P=0.263 or P=0.372, respectively). For the identification of cirrhosis, sequential FIB-4-TE and APRI-TE algorithms saved a significantly higher number of liver biopsies than TE alone (83.2% or 88.3% vs 69.8%, P=0.003 or P=0.000, respectively). No significant difference was found between the sequential algorithms and TE alone in the diagnostic accuracy for the detection of AF and cirrhosis. The sequential algorithms could significantly reduce the need for liver biopsy with high accuracy for diagnosis of AF and cirrhosis in CHB patients, which would be optimal especially in resource-limited areas.

Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study

The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54-0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75-0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86-0·94]), ADAPT (0·85 [0·81-0·89]), and FibroScan liver stiffness measurement (0·83 [0·80-0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4-5]), then ADAPT (six [5-7]), MACK-3 (seven [6-8]), and PRO-C3 (nine [7-11]). None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. The Innovative Medicines Initiative 2 Joint Undertaking.

Utility and limitations of Hepascore and transient elastography to detect advanced hepatic fibrosis in HFE hemochromatosis

Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (Fib4) have been validated against liver biopsy for detecting advanced hepatic fibrosis in HFE hemochromatosis. We determined the diagnostic utility for advanced hepatic fibrosis of Hepascore and transient elastography compared with APRI and Fib4 in 134 newly diagnosed HFE hemochromatosis subjects with serum ferritin levels > 300 µg/L using area under the receiver operator characteristic curve (AUROC) analysis and APRI- (> 0.44) or Fib4- (> 1.1) cut-offs for AHF, or a combination of both. Compared with APRI, Hepascore demonstrated an AUROC for advanced fibrosis of 0.69 (95% CI 0.56–0.83; sensitivity = 69%, specificity = 65%; P = 0.01) at a cut-off of 0.22. Using a combination of APRI and Fib4, the AUROC for Hepascore for advanced fibrosis was 0.70 (95% CI 0.54–0.86, P = 0.02). Hepascore was not diagnostic for detection of advanced fibrosis using the Fib4 cut-off. Elastography was not diagnostic using either APRI or Fib4 cut-offs. Hepascore and elastography detected significantly fewer true positive or true negative cases of advanced fibrosis compared with APRI and Fib4, except in subjects with serum ferritin levels > 1000 µg/L. In comparison with APRI or Fib4, Hepascore or elastography may underdiagnose advanced fibrosis in HFE Hemochromatosis, except in individuals with serum ferritin levels > 1000 µg/L.

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients.

Liver disease due to metabolic dysfunction constitute a worldwide growing health issue. Severe obesity is a particularly strong risk factor for non-alcoholic fatty liver disease, which affects up to 93% of these patients. Current diagnostic markers focus on the detection of advanced fibrosis as the major predictor of liver-related morbidity and mortality. The most accurate diagnostic tools use elastography to measure liver stiffness, with diagnostic accuracies similar in normal-weight and severely obese patients. The effectiveness of elastography tools are however hampered by limitations to equipment and measurement quality in patients with very large abdominal circumference and subcutaneous fat. Blood-based biomarkers are therefore attractive, but those available to date have only moderate diagnostic accuracy. Ongoing technological advances in omics technologies such as genomics, transcriptomics, and proteomics hold great promise for discovery of biomarkers and increased pathophysiological understanding of non-alcoholic liver disease and steatohepatitis. Very recent developments have allowed for single-cell sequencing and cell-type resolution of gene expression and function. In the near future, we will therefore likely see a multitude of breakthrough biomarkers, developed from a deepened understanding of the biological function of individual cell types in the healthy and injured liver.

Performance of Noninvasive Liver Fibrosis Tests in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is highly prevalent in morbidly obese patients, and fibrosis is an independent predictor of mortality. Noninvasive tests (NITs) are being developed for the detection of advanced fibrosis (AF).PurposeTo assess the performance of three NITs (NAFLD fibrosis score, NFS, fibrosis-4 index, FIB-4, and aspartate aminotransferase-to-platelet ratio, APRI), in the identification of AF among morbidly obese patients.Materials and MethodsPatients, who underwent bariatric surgery between 2004 and 2009 and had liver biopsy, were included. Fibrosis stages ≥ F2 and ≥ F3 were defined as significant and AF, respectively. Published and optimal thresholds (Youden index) for NFS, FIB-4 and APRI, sensitivity, specificity, positive and negative predictive values (PPV-NPV), and area under the receiver operator curves (AUROC) were evaluated.ResultsAmong 584 patients (mean age 43.3 ± 11.3 years, 21.2% male, 75% white, mean BMI 45.5 ± 8.80), 31.7% had NASH. Stages distributions were F1 = 68.1%, F2 = 16.4%, F3 = 8%, and F4 = 3.2%. At published thresholds, all 3 NITs performed poorly for detection of AF, with AUROC < 0.62. Overall performance at optimal thresholds improved to 0.68, 0.72, and 0.74 for NFS, FIB-4, and APRI, respectively. At optimal thresholds, all tests had good NPV (94.4–95.9%) but low PPV (24.2–32.5%). Combinations of the tests did not improve their performance.ConclusionsNFS, FIB-4, and APRI fall short to detect advanced fibrosis but valuable for excluding advanced fibrosis. More research is needed to develop new NITs with high positive predictive value.

Serum matrix metalloproteinase 7 (MMP7) is a biomarker of fibrosis in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population globally. Since liver fibrosis is the most important predictor of liver-related complications in patients with NAFLD, identification of patients with advanced fibrosis among at-risk individuals is an important issue in clinical practice. Transient elastography is the best evaluated non-invasive method used in referral centres to assess liver fibrosis, however serum-based tests, such as the Enhanced Liver Fibrosis (ELF) score, have a practical advantage as first-line tests due to their wider availability and lower cost. We previously identified matrix metalloproteinase 7 (MMP7) as a serum biomarker of histological advanced fibrosis in a mixed-etiology patient cohort. In this study we aimed to determine the association between MMP7 and fibrosis, assessed by transient elastography, in patients with NAFLD. Serum MMP7 levels were measured in a cohort of 228 patients with NAFLD. Associations between MMP7, liver stiffness measurement (LSM), ELF score and clinical parameters were determined using logistic regression modelling. Serum MMP7 was associated with clinically significant fibrosis (LSM ≥ 8.2), independent of age, gender, BMI and diabetes. The addition of MMP7 significantly improved the diagnostic performance of the ELF test, particularly in patients over the age of 60. Combinations of serum biomarkers have the potential to improve the sensitivity and specificity of detection of advanced fibrosis in at-risk patients with NAFLD. We have demonstrated that serum MMP7 is independently associated with clinically significant fibrosis and improves the diagnostic performance of currently available tests in older patients.

SAT337 - Meta-analysis: accuracy of the enhanced liver fibrosis (ELF) test in detection of advanced fibrosis or cirrhosis

SAT337 - Meta-analysis: accuracy of the enhanced liver fibrosis (ELF) test in detection of advanced fibrosis or cirrhosis

Diagnostic Accuracy of Noninvasive Tests to Detect Advanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease

For patients with liver disease from hepatitis C virus (HCV) infection complicated by end-stage renal disease (ESRD), it is important to assess liver fibrosis before kidney transplantation. We evaluated the accuracy of non-invasive tests to identify advanced hepatic fibrosis in patients with HCV and ESRD. In a retrospective study, we collected data on ratio of aspartate aminotransferase:alanine aminotransferase (AST:ALT), AST platelet ratio index (APRI), FIB-4 score, fibrosis index score, and King's score from 139 patients with ESRD and HCV infection (mean age, 52.8 y; 76.3% male; 86.4% African American; 45.3% with increased level of ALT). Results were compared with findings from histologic analyses of biopsies (reference standard). The primary outcome was detection of advanced fibrosis, defined as either bridging fibrosis or cirrhosis. Area under the receiver operating characteristic (AUROC) curves were constructed and optimal cutoff values were determined for each test. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated. We repeated the analysis with stratification for normal levels of ALT (≤ 35 U/L for men and ≤ 25 u/L for women) and increased levels of ALT. FIB-4 scores identified patients with advanced fibrosis with an AUROC of 0.71 (95% CI, 0.61-0.80), the King's score with an AUROC of 0.69 (95% CI, 0.58-0.80), and the APRI with and AUROC of 0.68 (95% CI, 0.59-0.79). The accuracy of these tests increased when they were used to analyze patients with increased levels of ALT. All tests produced inaccurate results when they were used to assess patients with normal levels of AST and ALT. In patients with ESRD and HCV infection, FIB-4 scores, King's scores, and the APRI identify those with advanced fibrosis with AUROC values ranging from 0.68-0.71. Accuracy increased modestly when patients with increased levels of ALT were tested, but the tests produced inaccurate results for patients with a normal level of ALT.

Impact of Implementing a "FIB-4 First" Strategy on a Pathway for Patients With NAFLD Referred From Primary Care.

Detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is essential for stratifying patients according to the risk of liver‐related morbidity. Noninvasive methods such as vibration‐controlled transient elastography (VCTE) and Fibrosis‐4 index (FIB‐4) have been recommended to identify patients for further assessment. The aim of this study was to assess the potential impact of implementing a “FIB‐4 First” strategy to triage patients entering a NAFLD assessment pathway. The pathway for patients with suspected NAFLD was piloted at a tertiary liver center. Referral criteria were 16‐65 years old, elevated alanine aminotransferase and/or steatosis on imaging, and absence of a previous liver diagnosis. A registered nurse risk‐stratified all patients based on VCTE and FIB‐4 was calculated. Potential alternative diagnoses were excluded with bloodwork. A total of 565 patients underwent risk stratification with VCTE with a 97% success rate. Ten percent had VCTE of at least 8 kPa; 560 patients had FIB‐4 available for analysis and 87% had values less than 1.3. Of those with a FIB‐4 of at least 1.3, 69% had a VCTE less than 8 kPa. Further modeling showed that the presence of diabetes, age, and body mass index had only a moderate impact on the association between FIB‐4 and elastography values if using a FIB‐4 threshold of 1.3. Conclusion: A FIB‐4 threshold of 1.3 was acceptable for excluding the presence of advanced fibrosis (assessed by VCTE). A staged risk‐stratification model using FIB‐4 and VCTE could save up to 87% of further assessments. This model could improve accessibility by moving the initial fibrosis evaluation to the medical home and helping to prioritize patients for further specialized care.

Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage

Noninvasive methods are needed to determine disease stage in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic performance of several widely available fibrosis models for the assessment of hepatic fibrosis in patients with NAFLD. We performed a retrospective analysis of data from individuals enrolled in the NIDDK NASH Clinical Research Network, from 2004 through 2018. Using biopsy as the reference standard, we determined the diagnostic performance of the aspartate aminotransferase (AST):platelet ratio (APRI), FIB-4, ratio of AST:alanine aminotransferase (ALT) and the NAFLD fibrosis score (NFS) in a cross-sectional study of 1904 subjects. The ability of these models to detect changes in fibrosis stage was assessed in a longitudinal data set of 292 subjects with 2 biopsies and accompanying laboratory data. Outcomes were detection of fibrosis of any stage (stages 0-4), detection of moderate fibrosis (stages 0-1 vs 2-4), and detection of advanced fibrosis (stages 0-2 vs 3-4). Diagnostic performance was evaluated using the C-statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) analyses. In the cross-sectional study, FIB-4 and NFS outperformed other non-invasive models for detecting advanced fibrosis; the C-statistics were 0.80 for FIB-4 and 0.78 for NFS. In the longitudinal study, 216 patients had non-advanced fibrosis at baseline and 35 patients progressed to advanced fibrosis after median follow up of 2.6 years. After we adjusted for fibrosis stage and model score at initial biopsy, change in APRI, FIB-4, and NFS were significantly associated with change in fibrosis. A unit change in APRI, FIB-4, or NFS was associated with changes in fibrosis stage of 0.33 (95% CI, 0.20-0.45; P < .001), 0.26 (95% CI, 0.15-0.37; P < .001), and 0.19 (95% CI, 0.07-0.31; P= .002), respectively. The cross-validated C-statistic for detecting progression to advanced fibrosis for APRI was 0.82 (95% CI, 0.74-0.89), for FIB-4 was 0.81 (95% CI, 0.73-0.81), and for NFS was 0.80 (95% CI, 0.71-0.88). In a combined analysis of data from 2 large studies, we found that FIB-4, APRI, and NFS can detect advanced fibrosis and fibrosis progression in patients with NAFLD.

Criteria to Determine Reliability of Noninvasive Assessment of Liver Fibrosis With Virtual Touch Quantification

Virtual Touch Quantification (VTQ) evaluates liver fibrosis in patients with chronic liver diseases by measuring shear wave speed in the liver. We aimed to determine the reliability criteria of VTQ examination. We performed a prospective study of 1094 patients with chronic liver disease from November 2009 through October 2016 at Angers University Hospital, and between April 2010 and May 2015 at Bordeaux University Hospital, in France. All patients underwent liver biopsy analysis (reference standard), and VTQ examination was made by experienced operators on the same day, or no more than 3 months before or afterward. Advanced liver fibrosis was defined as fibrosis stage F ≥ 3 according to the scoring system of the Nonalcoholic Steatohepatitis Clinical Research Network, or fibrosis stage F ≥ 2 according to the Metavir scoring system. The diagnostic accuracy of VTQ in detection of advanced fibrosis or cirrhosis was assessed using the area under the receiver operating characteristic (AUROC) and the rate of correctly classified patients. Reliability criteria were defined from the intrinsic characteristics of VTQ examination, which were shown to influence the diagnostic accuracy. VTQ identified patients with advanced fibrosis with an AUROC of 0.773 ± 0.014 and correctly classified 72.0% of patients using a diagnostic cut-off value of 1.37 m/s. VTQ identified patients with cirrhosis with an AUROC value of 0.839 ± 0.014 and correctly classified 78.4% of patients using a cut-off value of 1.87 m/s. The reliability of VTQ decreased with an increasing ratio of interquartile range/median (IQR/M) in patients with intermediate-high VTQ results. We defined 3 reliability categories for VTQ: unreliable (IQR/M ≥0.35 with VTQ result ≥1.37 m/s), reliable (IQR/M ≥0.35 with VTQ result <1.37 m/s or IQR/M 0.15-0.34), and very reliable (IQR/M <0.15). For advanced fibrosis, VTQ correctly classified 57.8% of patients in the unreliable group, 73.7% of patients in the reliable group, and 80.9% of patients in the very reliable group (P < .001); for cirrhosis, these values were 50.0%, 83.4%, and 92.6%, respectively (P < .001). Of the VTQ examinations made, 21.4% were unreliable, 55.0% were reliable, and 23.6% were very reliable. The skin-liver capsule distance was independently associated with an unreliable VTQ examination, which occurred in 52.7% of patients with a distance of 30 mm or more. In a study to determine the reliability of VTQ findings, compared with results from biopsy analysis, we assigned VTQ examinations to 3 categories (unreliable, reliable, and very reliable). VTQ examinations with IQR/M ≥0.35 and ≥1.37 m/s had very low diagnostic accuracy. Our reliability criteria for liver fibrosis assessment with VTQ will help physicians to accurately evaluate the severity of chronic liver diseases and monitor their progression.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease

Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n= 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n= 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P= .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P= .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P= .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.

Transient elastography as a predictor of oesophageal varices in patients with liver cirrhosis

One of the most serious complications of liver cirrhosis is variceal bleeding. Early recognition of the oesophageal varices is of primary importance in the prevention of variceal bleeding. Endoscopy is the only means to directly visualize varices and measure their size, as one of the most important predictor of the risk of bleeding. During the course of cirrhosis repeated oesophago-gastro-bulboscopic examinations are recommended. As these interventions are expensive and often poorly accepted by patients who may refuse further follow-up, there is a need for non-invasive methods to predict the progression of portal hypertension as well as the presence and the size of oesophageal varices. After several combinations of biological and ultrasonographical parameters proposed for the detection of advanced fibrosis, it was suggested that liver stiffness measured by transient elastography, a novel non-invasive technology may reflect not only fibrosis and portal pressure but it may even predict the presence or absence of large oesophageal varices in patients with cirrhosis. The aim of the authors was to study the diagnostic accuracy of transient elastography using FibroScan for selecting patients who are at risk of bearing large (Paquet-grade ≥ II) oesophageal varices and high risk of bleeding. The authors performed upper tract endoscopy and transient elastography in 74 patients with chronic liver disease (27 patients with chronic hepatitis and 47 patients with liver cirrhosis). The relationships between the presence of oesophageal varices (Paquet-grade 0-IV) and liver stiffness (kPa), as well as the hematological and biochemical laboratory parameters (prothrombine international normalized ratio, platelet count, aspartate aminotransferase, alanine aminotransferase, albumin, and aspartate aminotransferase/platelet ratio index) were investigated. The predictive role of liver stiffness for screening patients with varices and those who are at high risk of variceal bleeding was also analysed. Liver stiffness values significantly correlated with the grade of oesophageal varices (Paquet-grade) (r = 0.67, p<0.0001). The liver stiffness value of 19.2 kPa was highly predictive for the presence of oesophageal varices (AUROC: 0.885, 95% CI: 0.81-0.96) and for the presence of high grade varices (P≥II) (AUROC: 0.850, 95% CI: 0.754-0.94). Using the cut-off value of 19.2 kPa, the sensitivity of transient elastography was 85%, specificity was 87%, positive predictive value was 85%, negative predictive value was 87% and validity was 86% for the detection of varices. Liver stiffness values less than 19.2 kPa were highly predicitive for the absence of large (P≥II) varices (sensitivity, 95%; specificity, 70%; positive predictive value, 54%; negative predictive value, 97%). Transient elastography may help to screen patients who are at high risk of bearing large (P≥II) oesophageal varices which predict variceal bleeding and, therefore, need endoscopic screening. Lives stiffness values higher than 19.2 kPa indicate the need for oesophageal-gastro-bulboscopy, while liver stiffness values lower than 19.2 kPa make the presence of large oesophageal varices unlikely.

Performance of transient elastography (TE) and factors associated with discordance in non‐alcoholic fatty liver disease

To determine the accuracy of transient elastography (TE) and factors associated with discordance between TE and liver histology in patients with non-alcoholic fatty liver disease (NAFLD). The accuracy of TE was assessed and compared with the aspartate aminotransferase-to-platelet ratio index (APRI) in patients with histologically proven NAFLD. Factors associated with discordance between liver histology and TE were analyzed. Altogether 131 patients with a mean age of 49.9 years, including 69 men and 62 women, with NAFLD underwent liver stiffness measurement (LSM) by TE. Among all patients, 120 (91.6%) had a successful LSM with an interquartile to median ratio of 0.15. The accuracy of TE in detecting ≥F3 and F4 fibrosis, assessed by the area under the receiver operating characteristic curve, were 0.77 and 0.95, respectively. The sensitivity and specificity of the optimal LSM cut-off values for detecting ≥F3 fibrosis (sensitivity 70.4% and specificity 66.6%) and F4 (sensitivity 87.5% and specificity 89.3%) were modest, but better than those of APRI. Discordance between TE and histology for fibrosis grading was observed in 22.5% of patients, but it could not be explained by body mass index, alanine aminotransferase level, the length of the biopsied specimens or the grade of steatosis. TE plays an important role in the detection of advanced fibrosis and cirrhosis in patients with NAFLD and its accuracy does not appear to be influenced by components of the disease.

Estudio retrospectivo de la capacidad de evaluación de fibrosis hepática del FibroScan ®, APRI, FIB-4 y FORNS con referencia a la biopsia hepática de pacientes con hepatitis crónica C, mono y coinfectados con VIH

Objective To assess the ability of FibroScan ® (FS) and the APRI, FIB-4 and FORNS indexes to predict liver fibrosis (LF), using liver biopsy as the gold standard. Methods LF stage was determined in 154 patients with chronic hepatitis C virus infection using the METAVIR system. Fibroscan ® measurements and blood samples were taken simultaneously with biopsy. The tests were evaluated using ROC curves and the concordance, sensitivity, specificity and predictive values and likelihood ratios. Results Significantly higher LF stages were found in older patients and in those with HIV coinfection. FS and FIB-4 were able to predict significant LF≥1 and more than 94% of patients with FS>6.7 kPas or FIB-4>1.3 had LF≥1 in liver biopsy, with low sensitivities (63% FS; 56% Fib-4). For the detection of LF≥2, all the tests had significant predictive capacity and between 77% and 86% of the patients with FS>6.8kPas, APRI>0.6, FIB-4>1.4 and FORNS>5.6 had LF≥2, with low sensitivities (70%FS; 54%APRI; 59%FIB-4; 54%FORNS). All tests had high negative predictive values (91–92%) and specificities (86–92%) in the detection of advanced fibrosis (FH=4). Conclusion All tests were acceptable in predicting the presence or absence of mild fibrosis (LF≥2) and the absence of advanced fibrosis (LF=2). However, the low or moderate agreement with liver biopsy and low sensitivities in the detection of mild fibrosis indicate that liver biopsy continues to be required when the results of other methods are discordant or indeterminate.

PWE-048 Performance of simple algorithm tests for the detection of fibrosis in non-alcoholic fatty liver disease: Abstract PWE-048

Aim The aim of this study was to assess the performance of several simple algorithm tests for the detection of advanced fibrosis in NAFLD. Introduction NAFLD is an increasingly common clinical entity and represents a significant burden in both primary and specialist care settings. Histological evaluation remains the gold standard investigative tool, although there is an increasing need for non-invasive assessment and categorisation. Several simple algorithm tests, utilising both simple biochemical and anthropological measurements have been designed to detect severe forms of fatty liver. This is an attractive proposition especially in the triage of patients either by the Primary care physician or the hepatologist who are confident of the diagnoses of NAFLD in their patients but would like to stratify them further between simple steatosis and steatohepatitis with fibrosis. Methods We retrospectively applied seven scoring algorithms to 42 patients with biopsy proven NAFLD. All patients had negative liver screens and consumed Results Please see Abstract 048. Where the test correctly predicted the presence of non-advanced disease, we assigned that patient as a potentially avoidable biopsy. Conclusion Scoring systems employing routinely available clinical and biochemical markers are useful in the detection of advanced fibrosis in NAFLD. Simple scoring systems (AST/Plt, AST/ALT) perform as well as more complex algorithms (NAFLD-f). Application of simple scoring systems may reduce the number of biopsy performed.

Imaging of Nonalcoholic Steatohepatitis: Advantages and Pitfalls of Ultrasonography and Computed Tomography

The present study was performed to clarify the ability of ultrasonography (US) and computed tomography (CT) to detect steatosis and advanced fibrosis in nonalcoholic steatohepatitis (NASH) patients, and to assess the influence of steatosis, fibrosis, and obesity on the radiological detection of steatosis and advanced fibrosis. One hundred and eighteen biopsy proven NASH patients underwent US and CT within 6 months before or after biopsy. The ability of US and CT to detect histological steatosis and advanced fibrosis was assessed. To evaluate whether fibrosis and obesity interfered with the detection of moderate to severe histological steatosis by US and CT, we analyzed 88 NASH patients with moderate to severe steatosis. To evaluate interference with the detection of advanced fibrosis by steatosis and obesity, we analyzed 59 NASH patients with advanced fibrosis. The sensitivity of US for detecting moderate to severe histological steatosis in patients with mild histological fibrosis was 100%, but this was reduced to 77.8% in patients with advanced histological fibrosis (p=0.001). The sensitivity of CT was 69.8% in patients with mild histological fibrosis and 48.9% in those with advanced histological fibrosis (p=0.047). The sensitivity of US and CT for moderate to severe histological steatosis was similar in each body mass index group. The sensitivity for detecting advanced fibrosis was markedly decreased by severe steatosis and obesity in the case of both US and CT. If we are aware of these disadvantages of US and CT, it is useful for diagnosing steatosis and fibrosis in NAFLD patients.

M1572 AST/ALT, APRI, and Magnetic Resonance Elastography for Detection of Advanced Fibrosis in Clinical Practice

M1572 AST/ALT, APRI, and Magnetic Resonance Elastography for Detection of Advanced Fibrosis in Clinical Practice