Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for significant fibrosis and cirrhosis in chronic hepatitis B.
ABSTRACT: Assessing the diagnostic performances of APRI and FIB-4 using age as a categorical marker.822 chronic hepatitis B (CHB) patients were included. Using METAVIR scoring system as a reference, the performances of APRI and FIB-4 were compared between patients aged≥30 and patients aged<30 years.The APRI AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis (0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.57 vs 0.65, p<0.001) and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity≥90%, the APRI cut-off in patients aged<30 years was lower than patients aged≥30 years for significant fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity≥90%, the APRI cut-off in patients aged<30 years was also lower than patients aged≥30 years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using specificity≥90%, the FIB-4 cut-off in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis (1.4 vs 2.6). Using sensitivity≥90%, the FIB-4 cut-off in patients aged<30 years was also lower than that in patients aged≥30 years for significant fibrosis (0.5 vs 0.8) and cirrhosis (0.8 vs 1.2).Evaluation of the diagnostic performances of APRI and FIB-4 should take age into consideration.
Project description:BACKGROUND & AIMS:The value of liver stiffness measurement (LSM) by transient elastography (TE) for non-invasive fibrosis staging and disease monitoring has not been established in patients with Wilson disease (WD). METHODS:Liver stiffness measurement by TE and non-invasive fibrosis scores (APRI, FIB-4) were analysed from 188 WD patients with liver biopsy (LBX). Longitudinal LSM was performed in 128 (68.1%) patients. RESULTS:One hundred and eighty-eight patients (mean age: 35 ± 14 years, 54.8% women; 27.1% with histological cirrhosis) were studied. Forty-four[23.4%] patients were recently diagnosed with WD, while 144[76.6%] were previously diagnosed (>1 year between LBX and LSM). Overall, LSM (11.3 vs 6.1 kPa, P < .001), APRI (0.72 vs 0.38, P < .001) and FIB-4 (1.54 vs 0.89, P < .001) were higher in cirrhotic than in non-cirrhotic patients. This was even more pronounced in recently diagnosed patients (35.2 kPa vs 6.4 kPa, P < .001). Accuracy for diagnosing cirrhosis at an LSM cut-off ?9.9 kPa was better in recently diagnosed (PPV: 74%, NPV: 100%) vs previously diagnosed (PPV: 53%, NPV: 82%) patients. Recently diagnosed patients had higher Area Under the Curve (AUC) for APRI (0.79 vs 0.61) and FIB-4 (0.84 vs 0.65) than previously diagnosed patients. At APRI <1.5 and FIB-4 <3.25 cirrhosis was ruled out with a specificity of 93% and 95% respectively. During a median follow-up of 46 (24-66) months, only 5.9% (5/85) of non-cirrhotic WD patients showed progression to cirrhotic LSM values, while 30.8% (4/13) of cirrhotic WD patients showed LSM suggestive of cirrhosis regression. CONCLUSION:TE-based LSM ?9.9 kPa accurately identifies cirrhosis in WD patients. Next to TE-LSM <9.9 kPa, APRI <1.5 and FIB-4 <3.25 values assist to non-invasively rule out cirrhosis. LSM remains stable in most non-cirrhotic patients on WD therapy, while one-third of cirrhotic patients present clinically relevant decreases in LSM.
Project description:We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients.The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative (n = 213) and high-replicative (HBV DNA ?20,000 IU/mL, n = 153) patients was assessed.Overall, 113 patients (30.9%) had F2-4 fibrosis. Of the low and high-replicative patients, 40 (18.8%) and 73 (47.7%) had F2-4, respectively (P < 0.0001). APRI ?0.5 less frequently identified F2-4 fibrosis in low vs. high-replicative patients (48.7% vs. 69.6%, P = 0.032) and AAR identified it more frequently in low-replicative patients (37.5% vs. 19.4%, P = 0.037). FIB-4 and API were not different (P > 0.05) for identifying F2-4 fibrosis in low and high-replicative patients. Higher specificities were seen at the lowest cut-offs in low vs. high-replicative states for APRI (?0.5, 98% vs. 68.9%), AAR (84.3% vs. 76.6%), FIB-4 (?1.45, 97.5% vs. 87.8%) and API (>4, 94.8% vs. 93.8%). At ROC-defined thresholds, APRI (?0.33), AAR (?0.93), FIB-4 (?0.70) and API (>2) showed greater AUROCs for F2-4 diagnosis in low replicative (0.80, 0.62, 0.81 and 0.71, respectively) vs. high-replicative patients (0.73, 0.52, 0.67 and 0.69, respectively).All 4 biomarkers in both, low and high-replicative HBV demonstrate modest accuracy for fibrosis diagnosis at conventional cut-offs. Lowering the cut-offs may increase the diagnostic relevance of these biomarkers, particularly for APRI and FIB-4 in low-replicative disease.
Project description:BACKGROUND:Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) virus but have not been evaluated in chronic hepatitis D virus (HDV). AIM:To evaluate the utility of serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, aspartate aminotransferase ratio (AAR), age-platelet index (API), AST-to-platelet-ratio-index (APRI) and Hui score] in HDV infection. METHODS:Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ?4) and cirrhosis (Ishak = 6) were evaluated and compared between viral infections. RESULTS:A total of 1003 subjects (HCV = 701, HBV = 240 and HDV = 62) with mean age of 46 ± 11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak ?4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4 = 0.70 (0.55-0.84), API = 0.69 (0.55-0.82), APRI = 0.68 (0.54-0.82), Hui score = 0.63 (0.49-0.78), AAR = 0.63 (0.48-0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4 = 0.83 (0.69-0.97), API = 0.80 (0.66-0.95), APRI = 0.75 (0.61-0.89), Hui score = 0.70 (0.49-0.91) and AAR = 0.70 (0.48-0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. CONCLUSIONS:Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.
Project description:Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with chronic hepatitis B (CHB) and C (CHC). The expression of 13 fibrosis-related microRNAs (miRNAs) (miR-20a, miR-21, miR-27a, miR-27b, miR-29a, miR-29c, miR-92a, miR-122, miR-146a, miR-155, miR-221, miR-222, and miR-224) was analyzed in 194 serums and 177 liver biopsies of patients with either CHB or CHC to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3-F4). In CHB patients, the model (serum miR-122, serum miR-222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB-4 to discriminate in between mild and moderate fibrosis (F1-F2) and F3-F4 (AUC of CHB model: 0.85 vs APRI: 0.70 and FIB-4: 0.81). In CHC patients, the model (hepatic miR-122, hepatic miR-224, platelet count, albumin and alanine aminotransferase) was more accurate than both APRI and FIB-4 to discriminate in between patients with F3-F4 and F1-F2 (AUC of the CHC model?=?0.93 vs APRI: 0.86 and FIB-4: 0.79). Most of the miRNAs tested were differentially expressed in patients with CHB and CHC. In particular, serum miR-122 was 28-fold higher in patients with CHB than in those with CHC. Both CHB and CHC models may help for the diagnosis of advanced fibrosis and cirrhosis (F3-F4).
Project description:BACKGROUND AND AIM:The aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level. METHODS:This retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997-2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST?37 IU/L (N = 132), 37<AST?74, (N = 501), 74<AST?148 IU/L (N = 737), and AST>148 IU/L (N = 346). RESULTS:436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST?37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37<AST?74IU/L; 0.72 for APRI and 0.73 for FIB-4 in patients with 74<AST?148 IU/L; and 0.68 for APRI and 0.70 for FIB-4 in patients with AST>148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST?37 IU/L; 1.1 and 2.2, respectively, in patients with 37<AST?74 IU/L; 2.2 and 3.4, respectively, in patients with 74<AST?148 IU/L; and 3.4 and 5.5, respectively, in patients with AST>148 IU/L. CONCLUSIONS:We provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.
Project description:OBJECTIVE:To examine the accuracy of noninvasive inflammatory markers in predicting liver fibrosis stage in patients with autoimmune hepatitis (AIH). PATIENTS AND METHODS:We enrolled 55 patients with AIH and 60 healthy controls in this study, and divided them into three groups: F0 (control); F1-F3 (noncirrhotic fibrosis); and F4 (cirrhosis). The following markers were analyzed for all participants: lymphocyte-to-neutrophil ratio (LNR); lymphocyte-to-platelet ratio (LPR); lymphocyte-to-monocyte ratio (LMR); immunoglobulin-to-platelet ratio (IGPR); aminotransferase-to-platelet ratio index (APRI); aspartate aminotransferase-to-alanine aminotransferase ratio (AAR); and fibrosis-4 score (FIB-4). The predictive accuracy of these noninvasive markers was assessed using area under the receiver operating characteristic curve. Multivariate ordinal logistic regression models were used to analyze associations between the noninvasive markers and liver fibrosis stage. RESULTS:AAR, LPR, LMR, IGPR, APRI, and FIB-4 were linked to liver fibrosis-stage (P < 0.05), with correlation indices of - 0.219, 0.258, - 0.149, 0.647, 0.841, and 0.704, respectively, but not LNR (P = 0.093). area under the receiver operating characteristic curves of LPR, IGPR, AAR, LMR, APRI, and FIB-4 for detecting cirrhosis (F4 vs. F0-F3) were 0.936 (95% confidence interval: 0.870-1.000, P < 0.001), 0.939 (0.875-1.000, P < 0.001), 0.528 (0.319-0.738, P = 0.768), 0.555 (0.409-0.700, P = 0.568), 0.798 (0.694-0.902, P = 0.002), and 0.881 (0.796-0.967, P < 0.001). Our multivariate ordinal regression analysis showed that LPR and IGPR were associated independently with liver fibrosis stage, with a coefficient of 0.385 (95% confidence interval: 0.103-0.667, P = 0.007) and 14.903 (2.091-27.786, P = 0.023), respectively. CONCLUSION:LPR and IGPR were associated independently with liver fibrosis stage in treatment-naive AIH, and were superior to APRI and FIB-4 in detecting cirrhosis.
Project description:Noninvasive biomarkers have been developed to predict hepatitis B virus (HBV)-related fibrosis owing to the significant limitations of liver biopsy. Those biomarkers were initially derived from evaluation of hepatitis C virus (HCV)-related fibrosis, and their accuracy among HBV-infected patients was under constant debate. A systematic review was conducted on records in PubMed, EMBASE and the Cochrane Library electronic databases, up until April 1st, 2013, in order to systematically assess the effectiveness and accuracy of these biomarkers for predicting HBV-related fibrosis. The questionnaire for quality assessment of diagnostic accuracy studies (QUADAS) was used. Out of 115 articles evaluated for eligibility, 79 studies satisfied the pre-determined inclusion criteria for meta-analysis. Eventually, our final data set for the meta-analysis contained 30 studies. The areas under the SROC curve for APRI, FIB-4, and FibroTest of significant fibrosis were 0.77, 0.75, and 0.84, respectively. For cirrhosis, the areas under the SROC curve for APRI, FIB-4 and FibroTest were 0.75, 0.87, and 0.90, respectively. The heterogeneity of FIB-4 and FibroTest were not statistically significant. The heterogeneity of APRI for detecting significant fibrosis was affected by median age (P?=?0.0211), and for cirrhosis was affected by etiology (P?=?0.0159). Based on the analysis we claim that FibroTest has excellent diagnostic accuracy for identification of HBV-related significant fibrosis and cirrhosis. FIB-4 has modest benefits and may be suitable for wider scope implementation.
Project description:Recently, modified fibrosis-4 index (mFIB-4) and the easy liver fibrosis test (eLIFT) were developed for predicting liver fibrosis in chronic liver disease patients. We evaluated whether the 2 tests can predict hepatocellular carcinoma (HCC) risk in alcoholic liver cirrhosis (ALC) patients.A retrospective cohort of 924 ALC patients was assessed for HCC development. Four non-invasive serum biomarkers, mFIB-4, the eLIFT score, fibrosis-4 index (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were tested using time-dependent analysis of areas under receiver operating characteristic curve (AUROC), DeLong, and log-rank tests.During a median 4.8 years of follow-up, HCC occurred in 83 patients (9.0%). For predicting HCC development at 3 years, the mFIB-4 showed a significantly higher AUROC than APRI and eLIFT scores (0.71 vs 0.61 and 0.56, respectively, all P?<?.05). The AUROCs of the mFIB-4 for HCC development were not significantly different from those of the FIB-4. According to the mFIB-4, the risk of HCC development was significantly stratified by low index (?4)/high index (>4) (P?<?.001 by log-rank test).The mFIB-4 showed better predictability of HCC development than APRI and eLIFT scores, and significantly stratified HCC risk in Asian ALC patients.
Project description:To investigate the association between serum complement 5a (C5a) concentration and liver fibrosis and cirrhosis in a large cohort of patients chronically infected with hepatitis B virus (HBV).Five hundred and eight patients with chronic HBV infection undergoing liver biopsy were included. Serum concentrations of C5a was measured by Luminex screening system. Ishak histological system was obtained.C5a levels were negatively associated with liver fibrosis stages and significantly declined in patients with severe fibrosis and cirrhosis (P < 0.001). Multiple analysis showed C5a, AST, laminin, Co-IV, platelet count, albumin, HBsAg associated with liver fibrosis independently. Based on the markers above, we created two scores, Fib-model for significant fibrosis and Cirrh-model for earlier cirrhosis. Fib-model was performing better to differentiate from significant fibrosis, with an AUROC of 0.82 (95 % CI 0.78, 0.86), in comparison to existed models APRI, FIB-4 and Forns' index with AUROCs of 0.71 (95 % CI 0.66, 0.76), 0.72 (95 % CI 0.67, 0.77), 0.77 (95 % CI 0.72, 0.81), respectively. Although, Cirrh-model showed AUROC of 0.85 (95 % CI 0.80, 0.91) for evaluation of earlier cirrhosis, superior to APRI, and Forns' index, C5a + FIB-4 performed best with an AUROC of 0.94 (95 % CI 0.90, 0.97).In patients with chronic HBV infection, serum C5a concentration significantly decreased in severe fibrosis stages and earlier cirrhosis. Fib-model and C5a + FIB-4 performed better than existed models for assessment of significant fibrosis and earlier cirrhosis, respectively.
Project description:To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients.Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals.Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years.TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.