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Beyond Biopsy: Real-World Evaluation of the FIB-6 Score in a Portuguese Cohort

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Introduction: Liver fibrosis is a key determinant of morbidity and mortality in chronic liver disease. Noninvasive scores such as Fibrosis-4 index (FIB-4) and AST to Platelet Ratio Index (APRI) are widely used, but their accuracy varies across populations. Fibrosis-6 score (FIB-6), a novel composite biomarker incorporating age, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, platelet count, and albumin improves fibrosis prediction. This study evaluated the diagnostic performance of FIB-6 in a Portuguese cohort with steatotic liver disease. Methods: This observational study analyzed 301 adult patients who underwent transient elastography. Demographic, clinical, and laboratory data were retrospectively collected. Noninvasive scores (FIB-4, APRI, and FIB-6) were calculated, and liver fibrosis (F0–F4) was assessed based on liver stiffness measure adjusted for liver disease etiology. Receiver operating characteristic (ROC) analyses, correlations with liver stiffness, Youden index–derived cutoffs, and rule-in/rule-out thresholds were subsequently performed. A subanalysis was also conducted for liver disease etiologies. Results: FIB-6 correlated moderately with liver stiffness (r=0.334; p<0.001), significantly outperforming FIB-4 and APRI, which showed weak or nonsignificant correlations. Area under the ROC Curve values for cirrhosis (F4) were 0.716 (FIB-6), 0.579 (APRI), and 0.513 (FIB-4); for advanced fibrosis (F3–F4), 0.709 (FIB-6), 0.568 (APRI), and 0.545 (FIB-4). Optimal Youden cutoffs for FIB-6 were >2.06 for advanced fibrosis and >1.69 for cirrhosis. A rule-in threshold of >2.30 achieved 90% specificity, while a rule-out threshold of <1.5 reached 90% sensitivity, for advanced fibrosis. FIB-6 outperformed FIB-4 and APRI across Metabolic Dysfunction–Associated Steatotic Liver Disease, Metabolic and Alcohol-Related Steatotic Liver Disease and Alcohol-Related Liver Disease. Discussion: FIB-6 demonstrated superior diagnostic performance compared to FIB-4 and APRI, showing greater accuracy in identifying advanced fibrosis and cirrhosis. Cut-off values varied across different etiologies, underscoring the importance of etiology-specific thresholds for optimal clinical application. Despite its robustness, laboratory-based scores may be influenced by physiological or clinical variations, requiring contextual interpretation. FIB-6 is a reliable and accessible noninvasive tool. Its application within a tripartite “rule-in/rule-out” framework can effectively guide clinical triage and prioritize patients for elastography, particularly in resource-limited settings.

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  • Research Article
  • Cite Count Icon 414
  • 10.1053/j.gastro.2008.03.001
Diagnosis and Quantitation of Fibrosis
  • May 1, 2008
  • Gastroenterology
  • Diarmuid S Manning + 1 more

Diagnosis and Quantitation of Fibrosis

  • Research Article
  • 10.7759/cureus.82014
Diagnostic Accuracy of Red Cell Distribution Width to Platelet Ratio for the Prediction of Liver Fibrosis in Patients With Chronic Liver Disease From Eastern India.
  • Apr 10, 2025
  • Cureus
  • D Pavan Sai Kumar Rao + 5 more

Background Early diagnosis of liver cirrhosis in patients with chronic liver disease (CLD) can help delay/prevent complications and thereby improve survival. The currently available diagnostic modalities for the non-invasive assessment of hepatic fibrosis, especially FibroScan, are costly and not widely available, whereas various non-invasive scores for the assessment of fibrosis are cumbersome. Hence, we aimed to develop an easy and simple score for predicting cirrhosis in patients from Eastern India suffering from CLD with a better diagnostic accuracy. Methodology This cross-sectional, observational study was conducted between September 2019 and September 2021 in East India. Our study participants were patients who had CLD of etiologies such as alcohol-related liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis B, chronic viral hepatitis C, primary biliary cholangitis, and autoimmune hepatitis, who had undergone FibroScan of the liver. All demographic details were noted, and the patients were subjected to physical examination, followed by hematological as well as biochemical investigations, including liver function tests. Non-invasive scores (such as aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 score (FIB-4) and red cell distribution width (RDW) to platelet ratio (RPR)) were computed, and their diagnostic accuracy for prediction of advanced fibrosis and cirrhosis were evaluated by receiver operating characteristic curve (ROC curve) analysis with comparison of area under the ROC curves.Pearson correlation and logistic regression analysis were also performed to study the association of these scores with advanced fibrosis and cirrhosis. Results The area under the ROC (AUROC) curve of the APRI score, FIB-4 score, RPR, and RPR × AST for prediction of advanced liver fibrosis was 0.817, 0.799, 0.706, and 0.811, respectively. Similarly, the AUROC of the above scores for the prediction of cirrhosis was 0.889, 0.858, 0.797, and 0.898. However, the product of RPR and AST was superior than APRI and FIB-4 for predicting cirrhosis. An RPR × AST value above the cut-off of 4.818 can help predict liver cirrhosis with 85.7% sensitivity and 85.5% specificity. Pearson correlation and logistic regression analysis also proved the association of these scores with liver fibrosis. Conclusions RPR is a simple, inexpensive, and easily available marker for predicting liver cirrhosis. Nevertheless, the variable RPR × AST can predict liver cirrhosis in patients with CLD with even greater diagnostic accuracy.

  • Research Article
  • Cite Count Icon 17
  • 10.1097/qad.0000000000002073
Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy
  • Mar 1, 2019
  • AIDS
  • Beatrice Christian + 11 more

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

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  • Cite Count Icon 1
Noninvasive assessment of liver fibrosis with aspartate transaminase to platelet ratio index (APRI)
  • Jul 1, 2011
  • Hepatitis Monthly
  • Michael Adler

Dear Editor, In chronic liver diseases, the management of patients must include a determination of the stage of fibrosis (to select specific therapies), a prognosis, the prevention of complications, and the surveillance of the disease. Over the past several years, significant progress has been made in improving noninvasive methods of assessing liver fibrosis. The risks of liver biopsy and the potential for sampling errors with regard to fibrosis staging support the use of noninvasive modalities including serum fibrosis markers or scores and elastography. The first are classified as direct (representing components of the extracellular matrix) or indirect (reflecting hepatic inflammation and function) and included in panels for clinical use. They include patented (i.e., Fibrotest, Fibrometer) and nonpatented (ASL/ALT ratio, APRI, FIB-4, Forns, ELF, Hepascore) tests. The majority of studies has involved patients with chronic HCV infection. Direct and indirect methods have demonstrated good to excellent performance in detecting significant disease (≥ F2) and cirrhosis (F4) [1]. Transient elastography (Fibroscan®), which measures liver stiffness, has excellent accuracy in detecting cirrhosis (F4) in chronic liver diseases [2]. The APRI (AST-to-platelet count ratio) is the most simple and cheapest indirect marker of inflammation and fibrosis [3]. Its diagnostic performance in detecting advanced fibrosis has been evaluated extensively [4], showing low sensitivity (41%), low negative predictive values (64%), good specificity (95%) and high positive predictive values (88%). In a study, a group of Turkish investigators presented their experience with the APRI in patients with chronic liver disease [5]. In a retrospective series of 455 patients (207 with HBV, 108 with HCV, and 140 with NAFLD) the low value [1] median Metavir fibrosis score with median values for APRI were reported 0.46, 0.49 and 0.43 respectively in the HBV, HCV and NAFLD groups. AUROC values for the detection of fibrosis (1 to 4) versus no fibrosis (F0) were 0.58, 0.54, and 0.62, respectively, in the 3 groups. Dr. Yilmaz and his team concluded that the APRI has acceptable accuracy in assessing liver fibrosis in patients with HCV and NAFLD but not in those with HBV. There are several drawbacks and flaws in this report that render its message unrealistic and erroneous. It was a retrospective series, without validation in an independent series, with 3 categories of etiologies, each comprising a limited number of patients. It was not a consecutive series, and the indication for liver biopsy was not mentioned, preventing the results from being applicable to other clinicians throughout the world. Furthermore, it is difficult to understand the basis for the diagnosis of NAFLD: US detection of steatosis ≥ 1 and absence of other causes of liver disease. The main weaknesses of this study were that a poor marker was chosen and the use of a non-pertinent clinical endpoint (i.e., presence or of fibrosis not) in place of significant fibrosis (≥ F2) and cirrhosis (≥ F4) or advanced (≥ F3) fibrosis. Thus, it is not surprising that the APRI performed poorly, with AUROCs largely inferior to the minimal value of 80%, well accepted by the medical community [6]. Even Dr. Alberti's group in Italy [7], which has great experience with the APRI, admits that this test alone has poor and variable performance, even in the identification of cirrhosis (AUROCs from 0.61 to 0.94 and 0.69 to 0.88 for significant [i.e. ≥ F2] fibrosis) when used alone. They propose a model, called Sequential Algorithm for Fibrosis Evaluation = safe biopsy algorithm, in which APRI is used first, after which Fibrotest® is used as the second-line test in the setting of HCV and HBV, effecting 47% and 82% spared liver biopsies in significant fibrosis and cirrhosis, respectively. Our group also has experience with the APRI, and we sought to compare, independently from the promoters, its diagnostic accuracy using AUROCs for the prediction of significant, advanced, and cirrhosis in HCV and other etiologies. Fibrotest was the most effective, followed by FIB-4, FORNS, APRI, and Fibroindex, in order of decreasing accuracy. In the global series and the HCV series, the AUROCs of the APRI were 0.73 and 0.74 for the diagnosis of significant fibrosis, reinforcing the observation that the minimal cut-off of 80% was not reached. In conclusion, the APRI alone is inappropriate for use in assessing liver fibrosis.

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Aspartate transaminase to platelet ratio index (APRI) to assess liver fibrosis in patients with chronic liver disease
  • Jun 1, 2011
  • Hepatitis Monthly
  • Caterina Anania + 4 more

Dear Editor, In patients with chronic liver disease (CLD), liver biopsy is currently an indispensable reference method to assess inflammatory activity and fibrosis stage and thus to estimate prognosis and guide management decisions in such patients. Given that the presence of advanced fibrosis is a predictor of nonresponse, the decision [1] to begin antiviral therapy in cases of chronic viral hepatitis is highly influenced by the stage of liver fibrosis. For example, in chronic hepatitis C (CHC) patients, the stage of liver fibrosis is a predictor of response to interferon-based treatment. Despite these premises, liver biopsy has several disadvantages, including poor patient compliance, sampling error, limited usefulness for follow up, and poor intra- and interobservation agreements [2]. Considering these limitations, in the last decade clinical investigators have been searching for noninvasive methods to obtain accurate information about the fibrosis stage in patients with CLD. Accordingly, a noninvasive diagnostic test for liver fibrosis should be simple, available to wide audiences at limited expense, able to accurately identify disease stage, and sensitive enough to track changes in fibrosis induced by the natural course of disease progression or by therapy [3]. Serum biochemical tests, including direct and indirect markers of liver fibrosis, have been the subject of an intensive investigation, but their diagnostic accuracy has been reported to vary widely [3][4]. In this area, of great contemporary interest is the article by Yilmaz et al. on the usefulness of the aspartate transaminase to platelet ratio index (APRI) to assess liver fibrosis in patients with CLD [5]. APRI is a simple and cheap method to ascertain the ratio between AST and platelets and is easy to use in clinical practice. In patients with CHC, APRI performance has been reported to vary widely in diagnostic accuracy (sensitivities between 41% and 91% and specificities between 47% and 95%) for identifying significant fibrosis. A recent systematic review [6] showed that for significant fibrosis, an APRI threshold of 0.5 was 81% sensitive and 50% specific. Furthermore, Cheung et al. found that in patients with CHC, APRI was better in predicting advanced versus significant fibrosis, and the authors suggested that APRIs with a cutoff of 0.5 and 1.5 can be used in routine clinical practice to exclude or identify the presence of advanced fibrosis [7]. Consistent with the previous research, the retrospective study by Yilmaz et al.[5] showed that APRI has an acceptable accuracy for the assessment of liver fibrosis in patients with CHC but not in those with chronic hepatitis B (CHB). Indeed, in Yilmaz et al.'s study APRI was significantly associated with fibrosis scores in subjects with CHC (p = 0.0059) but not in those with CHB (p = 0.1495). The major finding of their study was that the APRI also had an acceptable accuracy for the assessment of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), tending to increase with the degree of fibrosis. In previous observational studies that included patients with NAFLD, the APRI score seldom reached the value of 1 but tended to be higher in patients with advanced stages of fibrosis [8]. In the early stages of NAFLD, patients usually present mild to moderate increases in aminotransferase levels, while platelet counts are usually normal. Fibrosis progresses over time, but it may remain stable for some years. Thus, the focus of the study by Yilmaz et al.[5] is that the APRI may be a useful asset in clinical practice to identify the natural course of NAFLD as it approaches the advanced stages. Nonetheless, much more information is needed on the potential uses of this index in the field of hepatology. More advanced stages of NAFLD appear to be associated with older age, higher BMI, diabetes, hypertension, high triglycerides, and insulin resistance [9]. The findings from different studies are not completely consistent as to which factors (including APRI score) are independently associated with fibrosis progression, and this may depend on the population studied.

  • Abstract
  • 10.14309/01.ajg.0000706776.35223.f9
S1182 A New Frontier of Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Estimation: Comparing APRI and NAFLD Fibrosis Score (NFS) to Assess Liver Fibrosis Levels in Patients With and Without Diabetes
  • Oct 1, 2020
  • American Journal of Gastroenterology
  • Scott Berger + 6 more

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the major chronic liver diseases impacting the world today. NAFLD can silently progress to fibrosis and lead to cirrhosis and hepatocellular carcinoma. Several non-invasive models have been developed using blood biomarkers to assess progression of fibrosis in patients with NAFLD. The aim of this study was to compare four of the most commonly used biomarker models in patients diagnosed with NAFLD to identify which of these models could best assess liver fibrosis in diabetic versus nondiabetic patients diagnosed with NAFLD. METHODS: This retrospective cohort study was performed at the Liver Associates of Texas Hepatology outpatient clinics in Houston, Texas from 9/2018 to 5/2020. Patients with other liver pathologies such as Hepatitis B, C, alcoholic liver disease, or hepatocellular cancer were excluded. Patients’ fibrosis levels were measured through two different modalities: lab serology and transient elastography through Fibroscan®. Using serology results, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), BARD, and NAFLD fibrosis score (NFS) were calculated and compared to kilopascals (kPa) measurements on elastography. A multivariate linear regression was used to compare the four models and assess their correlation with the kPa measurements in patients with and without diabetes. RESULTS: One hundred seventy patients were identified for this study. The mean age of patients was 55 years, 112 (66%) were female, and 79 (46%) had diabetes. APRI, BARD, and NFS scores significantly correlated with fibrosis level for all patients studied. When isolating diabetic patients, NFS was the only score that significantly correlated with advanced fibrosis level (68% sensitivity, 80% specificity). The NFS was not significantly correlated with advanced fibrosis in the non-diabetic group (18% sensitivity, 98% specificity). APRI and FIB-4 scores were the only scores that were significantly correlated with advanced fibrosis in non-diabetic patients. CONCLUSION: In NAFLD patients without other liver pathologies, APRI, BARD, FIB-4, and NFS models were all identified to be the indirect measures of fibrosis. The NFS demonstrated greater sensitivity of advanced fibrosis in diabetic patients than in nondiabetic patients. APRI score was more sensitive in nondiabetic patients compared to diabetics. This study emphasizes the relative strengths of the different fibrosis serology models in particular populations and warrants further review.Table 1.: Multivariate Regression of Indirect Fibrosis ModelsTable 2.: Epidemiological Tests Comparing APRI & NFS Scores for Diabetic & Nondiabetic Patients

  • Research Article
  • Cite Count Icon 63
  • 10.1097/meg.0000000000000392
Transient elastography using Fibroscan is the most reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in alcoholic liver disease.
  • Sep 1, 2015
  • European Journal of Gastroenterology &amp; Hepatology
  • Michael Fernandez + 8 more

Fibroscan (FS) is a reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in chronic liver disease. However, there is no clear consensus with respect to the best FS cut-off values for use in alcoholic liver disease (ALD). The aims of this study were as follows: (a) to compare the performance of FS and different biochemical markers in ALD patients; (b) to assess the best FS cut-off values for the prediction of fibrosis stage in our ALD population; and (c) to assess the influence of aspartate aminotransferase (AST) values on FS. This retrospective study included 135 consecutive and compensated ALD patients who underwent liver biopsy between November 2006 and March 2012 at Erasme Hospital. FS, Fibrotest, FIB-4, aspartate aminotransferase to platelet ratio index (APRI), and Forns' scores were tested in all patients. The diagnostic accuracy of FS was 0.89 (95% confidence interval: 0.83-0.95) for the diagnosis of advanced fibrosis and 0.93 (95% confidence interval 0.90-0.97) for the diagnosis of cirrhosis. FS performed better than Fibrotest (0.81 and 0.88), APRI (0.65 and 0.75), Forns' (0.64 and 0.78), and FIB-4 (0.70 and 0.73). The optimal cut-off values of liver stiffness (LS) for predicting METAVIR fibrosis stage F≥3 and F4 disease were 10.3 and 18.0 kPa, respectively. AST showed a significant positive correlation with LS (r=0.24, P=0.001). However, exclusion of patients with AST more than 50 IU/l only lowered the LS cut-off for the diagnosis of F4 (14 vs. 18.0 kPa). FS is currently the most reliable noninvasive method for the diagnosis of advanced liver fibrosis and cirrhosis in ALD.

  • Discussion
  • Cite Count Icon 10
  • 10.1016/j.jhep.2021.10.008
Reply to: Correspondence on “EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update”
  • Nov 4, 2021
  • Journal of hepatology
  • Annalisa Berzigotti + 7 more

Reply to: Correspondence on “EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update”

  • Abstract
  • 10.1136/gutjnl-2019-bsgabstracts.210
PTU-001 Diagnostic accuracy of non-invasive liver fibrosis markers in young adults within the ALSPAC population-based cohort
  • Jun 1, 2019
  • Gut
  • Kushala Abeysekera + 7 more

IntroductionEarly identification of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ARLD) can potentially halt progression to cirrhosis by removing the insult. Concerns remain regarding diagnostic accuracy of non-invasive...

  • Research Article
  • Cite Count Icon 1
  • 10.3126/ajms.v10i4.23170
AST to platelet ratio index for predicting the in hospital mortality in chronic liver disease patients in tertiary care hospital
  • Jun 21, 2019
  • Asian Journal of Medical Sciences
  • Bs Nagaraja + 3 more

Background: Liver cirrhosis is the end result of chronic liver injury. Cirrhosis of liver may progressively deteriorate from a well-compensated state to decompensated conditions.&#x0D; Aims and Objective: Our study aims at evaluating the AST to Platelet Ratio Index (APRI) for predicting the in-hospital mortality and also comparing APRI, MELD and albumin for predicting in hospital mortality in chronic liver disease.&#x0D; Materials and Methods: Data of Patients with Chronic liver disease were retrospectively reviewed. MELD and APRI scores were calculated for the patients and results from ROC curves were analysed.&#x0D; Results: In our study conducted on 299 patients, the age distribution was between 18-64 years with mean age of patients being 46.47+/-10.9 years, sex ratio Male: Female: 266:37 with mortality rate of 17.7%. The area under curves of ROC of APRI, MELD and Albumin are 0.63, 0.76 and 0.55.&#x0D; Conclusion: APRI is an independent predictor of mortality. The prognostic performance of all 3 was comparable but MELD has better prognostic significance than APRI score.

  • Research Article
  • Cite Count Icon 22
  • 10.1097/md.0000000000002946
AST to Platelet Ratio Index Predicts Mortality in Hospitalized Patients With Hepatitis B-Related Decompensated Cirrhosis.
  • Mar 1, 2016
  • Medicine
  • Weilin Mao + 4 more

Aspartate aminotransferase to platelet ratio index (APRI) has originally been considered as a noninvasive marker for detecting hepatic fibrosis in patients with chronic hepatitis B and C. APRI has been used for predicting liver-related mortality in patients with chronic hepatitis C virus infection or alcoholic liver disease. However, whether APRI could be useful for predicting mortality in chronic hepatitis B virus (HBV) infection remains unevaluated. This study aims to address this knowledge gap.A total of 193 hospitalized chronic HBV-infected patients (cirrhosis, n = 100; noncirrhosis, n = 93) and 88 healthy subjects were retrospectively enrolled. All patients were followed up for 4 months. Mortality that occurred within 90 days of hospital stay was compared among patients with different APRI. APRI predictive value was evaluated by univariate and multivariate regression embedded in a Cox proportional hazards model.APRI varied significantly in our cohort (range, 0.16–10.00). Elevated APRI was associated with increased severity of liver disease and 3-month mortality in hospitalized patients with HBV-related cirrhosis. Multivariate analysis demonstrated that APRI (odds ratio: 1.456, P < 0.001) and the model for end-stage liver disease score (odds ratio: 1.194, P < 0.001) were 2 independent markers for predicting mortality.APRI is a simple marker that may serve as an additional predictor of 3-month mortality in hospitalized patients with HBV-related decompensated cirrhosis.

  • Research Article
  • Cite Count Icon 20
  • 10.21037/qims-19-849
Assessment of liver fibrosis with liver and spleen magnetic resonance elastography, serum markers in chronic liver disease
  • Jun 1, 2020
  • Quantitative Imaging in Medicine and Surgery
  • Xiao-Pei Wang + 7 more

The accurate assessment of liver fibrosis is essential for patients with chronic liver disease. A liver biopsy is an invasive procedure that has many potential defects and complications. Therefore, noninvasive assessment techniques are of considerable value for clinical diagnosis. Liver and spleen magnetic resonance elastography (MRE) and serum markers have been proposed for quantitative and noninvasive assessment of liver fibrosis. This study aims to compare the diagnostic performance of liver and spleen stiffness measured by MRE, fibrosis index based on the 4 factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and their combined models for staging hepatic fibrosis. One hundred and twenty patients with chronic liver disease underwent MRE scans. Liver and spleen stiffness were measured by the MRE stiffness maps. Serum markers were collected to calculate FIB-4 and APRI. Liver biopsies were used to identify pathologic grading. Spearman's rank correlation analysis evaluated the correlation between the parameters and fibrosis stages. Receiver operating characteristic (ROC) analysis evaluated the performance of the four individual parameters, a liver and spleen stiffness combined model, and an all-parameters combined model in assessing liver fibrosis. Liver stiffness, spleen stiffness, FIB-4, and APRI were all correlated with fibrosis stage (r=0.87, 0.64, 0.65, and 0.51, respectively, all P<0.001). Among the 4 individual diagnostic markers, liver stiffness showed the highest values in staging F1-4, F2-4, F3-4 and F4 (AUC =0.89, 0. 97, 0.95, and 0.95, all P<0.001). The AUCs of the liver and spleen stiffness combined model in the F1-4, F2-4, F3-4, and F4 staging groups were 0.89, 0.97, 0.95, and 0.96, respectively (all P<0.001). The corresponding AUCs of the all-parameters combined model were 0.90, 0.97, 0.95, and 0.96 (all P<0.001). The AUCs of the liver and spleen stiffness combined model were significantly higher than those of APRI, FIB-4 in the F2-4, F3-4, and F4 staging groups (all P<0.05). Both combined models were not significantly different from liver stiffness in staging liver fibrosis (all P>0.05). Liver stiffness measured with MRE had better diagnostic performance than spleen stiffness, APRI, and FIB-4 for fibrosis staging. The combined models did not significantly improve the diagnostic value compared with liver stiffness in staging fibrosis.

  • Research Article
  • 10.26355/eurrev_202306_32797
Serum biomarkers predictive of cirrhosis in alcoholic liver disease as an alternative to ARFI-SW elastography.
  • Jun 1, 2023
  • European review for medical and pharmacological sciences
  • R Cioarca-Nedelcu + 6 more

Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) index are noninvasive biomarkers that evaluate liver stiffness in patients with chronic viral hepatitis and are able to detect advanced hepatic fibrosis and cirrhosis. However, their usefulness in alcoholic liver disease (ALD), when compared with Acoustic Radiation Force Impulse- Shear Wave (ARFI-SW) elastography, is debatable. We sifted the files of all enrolled patients with ALD that were admitted to our Emergency hospital between January 2019 and December 2020. All patients had undergone ARFI-SW elastography, and APRI and FIB-4 scores were calculated. The performance of APRI and FIB-4 scores in the prediction of cirrhotic patients according to ARFI-SW elastography was evaluated. In total, 120 patients with ALD were evaluated. All of them were male and Caucasian, with a mean age of 55.54±12.4 years. The mean ARFI-SW elastography score was 1.57±0.7 m/s, the median APRI score was 0.68 (0.1-11.6) and the median FIB-4 score was 1.8 (0.2-19.4). Stages of liver fibrosis according to ARFI-SW elastography were evaluated as F0-1 in 21 (10.5%), F2 in 35 (26%), F3 in 52 (17.5%), and F4 in 92 (46%) patients. Based on ARFI-SW elastography fibrosis stage classification, we estimated the optimal APRI and FIB-4 scores to predict the presence of liver cirrhosis (F4) by using ROC curve analysis and the Youden index. The optimal APRI score for F4 patients was calculated as >1.52 [area under the curve (AUC) 0.875, 95% CI 0.809-0.919; p<0.001], giving sensitivity (Se) 81.2%, specificity (Sp) 81.4%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 86.1%. The optimal FIB-4 score for F4 patients was calculated as >2.77 (AUC 0.916, 95% CI 0.814-0.922; p<0.001), giving Se 83.8%, Sp 77%, 81.4 77%, and NPV 84.3%. APRI and FIB-4 scores can be used as screening tools in ALD for predicting cirrhosis instead of ARFI-SW elastography measurement, which is neither widely available nor an affordable method. Additional prospective studies are required in the future to confirm this finding.

  • Discussion
Commentary on: Noninvasive assessment of liver fibrosis using aspartate transaminase to platelet ratio index (APRI) in adult patients with chronic liver disease
  • May 1, 2011
  • Hepatitis Monthly
  • Mortada El-Shabrawi + 1 more

Dear Editor, We enjoyed reading the excellent article by Yilmaz and colleagues on noninvasive assessment of liver fibrosis using aspartate transaminase to platelet ratio index (APRI) in adult patients with chronic liver disease (CLD) [1]. They performed their tests on adults with chronic hepatitis C (CHC), B (CHB), and non-alcoholic fatty liver disease (NAFLD). We definitely need to develop serological markers that have satisfactory sensitivity, specificity, and high predictive values, which can be used either instead of liver biopsy or to reduce the frequency of needed biopsies for monitoring the evolution of CHC and defining the right moment for commencing treatment. Despite the study results showing that APRI has an acceptable accuracy for the assessment of liver fibrosis in adults with CHC and NAFLD, this was not the case in CHB patients. We believe that the study results would have been more valid if the researchers have used a combination of non-invasive tests to assess liver fibrosis. A similar study conducted in Hungary used APRI and liver stiffness (LS) measurements to assess fibrosis in CHC [2]. The combination of both fibrosis markers was useful for non-invasive assessment of fibrosis in CHC. Forestier and colleagues found that LS measurements, APRI score, (13)C-amniopyrine breath test and indocyanine green plasma clearance were reliable markers for assessing cirrhosis in patients with CLD [3]. APRI was also found to be a simple and readily available tool for assessing liver fibrosis in patients with biliary atresia during post-operative follow-up care [4]. A drawback for using APRI is that its performance is not reliable in women, younger patients and in those with non-vertically-transmitted hepatitis C virus infection [5]. Alternatively, our group recommends the use of Fibrotest (FT) as a non-invasive serum biomarker for the assessment of the degree of hepatic fibrosis in pediatric patients with CHC. FT at a cutoff value of 0.25 was able to discriminate patients with mild stage of fibrosis from those with no or minimal fibrosis (sensitivity of 92.3%, specificity of 95.8% and accuracy of 94%). A higher cutoff point (FT = 0.54) can be used to diagnose significant fibrosis (ie., moderate or severe stages) with a sensitivity of 71.4%, specificity of 90.7%, and accuracy of 88.0% [6].

  • Research Article
  • Cite Count Icon 1
  • 10.3138/canlivj-2020-0008
Role of transient elastography and APRI in the assessment of pediatric cystic fibrosis liver disease.
  • Jan 4, 2021
  • Canadian liver journal
  • Jessica P Woolfson + 5 more

Diagnosis and monitoring of cystic fibrosis liver disease (CFLD) is challenging. Transient elastography (TE) is a rapid, non-invasive method for assessing liver fibrosis. Its role in detecting fibrosis in CFLD has only begun to be explored. The aspartate aminotransferase to platelet ratio index (APRI) has been validated as a predictor of hepatic fibrosis in other chronic liver diseases. The purpose of this study was to assess the utility of APRI and TE in identifying liver fibrosis in pediatric CF patients. Patients aged 2-18 years were recruited from the British Columbia Children's Hospital CF clinic. Patients were determined to have CFLD using standard criteria. Charts were reviewed, and each patient underwent TE. Of the 55 patients included in the study (50.9% male, mean age 11.6 y), 22 (40%) had CFLD. All mean liver enzymes were higher in the CFLD group, notably alanine transaminase (p = 0.031). Mean liver stiffness (LS) and APRI were also higher in the CFLD group (LS: 5.9 versus 4.5 kPa, p = 0.015; APRI: 0.40 versus 0.32, p = 0.119). Linear regression showed a mild positive association between the two (r 2 = 0.386). TE values were higher among CFLD patients and correlated with APRI values, suggesting that these tools may have clinical applications for identifying and following this population. Further research is needed on a larger scale to determine the relative value and clinical utility of TE and APRI among patients with CFLD.

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