Aspartate Aminotransferase-to-platelet Ratio Research Articles

Serum WFA+ -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection.

Accurate evaluation of liver fibrosis is crucial for predicting progression of chronic hepatitis B virus (HBV) infection. We assessed the utility of a novel fibrosis glycobiomarker Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) for evaluating liver fibrosis and disease progression in patients with chronic HBV infection. We enrolled 774 patients with chronic HBV infection, with or without fibrosis, diagnosed by liver biopsy/FibroScan. Patients who underwent liver biopsy (n = 297) were divided into training (n = 221) and validation (n = 76) groups. Serum WFA+ -M2BP values were measured and compared with FIB-4 index, aspartate aminotransferase (AST)-to-platelet ratio (APRI) and AST-to-alanine aminotransferase ratio (AAR) using receiver-operating characteristic (ROC) analysis. Serum WFA+ -M2BP levels increased significantly with fibrosis progression (P < 0.0001). Area under the ROC curve of WFA+ -M2BP for diagnosing significant fibrosis was higher than that of FIB-4 (P = 0.198), APRI (P = 0.017) and AAR (P < 0.001), with sensitivity and specificity in the training set of 60.5% and 79.8% and validation set of 59.5% and 82.1%, respectively. Serum WFA+ -M2BP levels were significantly correlated with FibroScan values (P < 0.0001) and improved the accuracy of FibroScan in assessing significant fibrosis. Changes in WFA+ -M2BP levels were parallel with those in FibroScan values during nucleot(s)ide analogues therapy in patients with chronic HBV infection. WFA+ -M2BP is an accurate serum indicator for assessing early stages of liver fibrosis and may monitor regression of fibrosis during the treatment of chronic HBV infection. WFA+ -M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan.

Serum platelet-derived growth factor BB levels: a potential biomarker for the assessment of liver fibrosis in patients with chronic hepatitis B.

Few studies have investigated serum levels of platelet-derived growth factor (PDGF) in patients with chronic hepatitis B (CHB). The present study aimed to determine whether PDGF-BB could serve as a potential biomarker for the detection of liver fibrosis. From October 2013 to August 2015, 465 patients with CHB were enrolled prospectively in this study. All patients underwent liver biopsy and staging based on the Ishak system. The serum PDGF-BB level was measured quantitatively by ELISA. The serum PDGF-BB level was negatively correlated with fibrosis stage in all patients (p = 0.003, Spearman's rho=-0.16) and was significantly different between fibrosis stages. The areas under the receiver operating characteristics curves (AUROCs) for serum PDGF-BB level and PGT score (a combination of PDGF-BB, gamma-glutamyl transpeptidase, and platelet levels) were 0.667 and 0.831, respectively, for patients with significant fibrosis and normal alanine aminotransferase (ALT) levels. The AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) were 0.823 and 0.821, respectively. Importantly, a cut-off value of 1.05 and 1.43, respectively, resulted in a sensitivity of 0.95 and 0.52, a specificity of 0.29 and 0.95, a positive predictive value of 0.30 and 0.79, and a negative predictive value of 0.96 and 0.86. The rate of correct diagnosis was up to 88.4% when using cut-offs of 1.05 and 1.43 for the absence or presence of significant fibrosis, respectively. Serum PDGF-BB decreased remarkably as fibrosis progressed, and this could be used as a non-invasive biomarker for the assessment of fibrosis stage in patients with CHB.

Noninvasive staging of fibrosis in patients with chronic Hepatitis C: correlation of FIB-4 and APRI to Fibroscan

Background and Aims: Treatment decisions with regimens containing direct acting antivirals (DAA) highly depend on accurate fibrosis staging. Fibroscan® has become a gold standard for non-invasive staging of fibrosis; however this method is not universally available. Thus, we compared the performance of Fibroscan® to the standardly available serologic tests AST to platelet ratio (APRI) and FIB-4.

Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.

Effect of glucocerebrosidase (GC) deficiency in osteoblasts on mineralization and osteoclastogenesis: Implications for bone pathology in Gaucher disease

Gaucher disease (GD) is one of the most common lysosomal diseases. It results from deficiency of the lysosomal enzyme glucocerebrosidase, which leads to accumulation of glucocerebroside and other glycolipids within the lysosomes of macrophages. Regarding liver involvement, hepatomegaly is universal and hepatic fibrosis typically occurs. Later in the disease, sinusoidal portal hypertension can be seen, but cirrhosis and hepatic failure are rare. Metabolic disorders are also common, and during enzymatic replacement therapy are characterized by hypometabolism and reduced levels of adiponectin which can be a risk factor for steatohepatitis. Transitory elastography (TE) is a novel non-invasive method for the assessment of hepatic fibrosis, by measuring liver stiffness. Controlled attenuation parameter (CAP), evaluated with transient elastography, is an efficient method to detect steatosis and define its grades. The AST-to-platelet ratio (APRI) can also be used to estimate fibrosis grade. For predicting significant fibrosis, an APRI cut-off of 0.7 had a sensitivity of 77% and a specificity of 72%. It was most studied in patients with hepatitis C. The aim of this study was to evaluate the hepatic involvement in a group of patients with GD, measuring fibrosis and steatosis by TE with CAP. We also compared the TE results with APRI index. Ten patients in treatment with taliglucerase were included. In 7 patients, TE values were compatible with fibrosis F0/F2 (lower than 9.5 kPA) and the APRI was lower than 0.7. In 2 patients, values were compatible with advanced fibrosis F4 (upper than 12.5 kPA) and APRI was higher than 0.7. In one patient, in whom the TE was difficult to perform because of obesity, there was a discordance between TE that was compatible with fibrosis (F0/F1) and the APRI (which was higher than 0.7). Concerning CAP values, 7 patients had values compatible with low, less than 11%, of steatosis. Two had values compatible with steatosis between 33–66% and 1 had a value compatiblewith steatosis greater than 67%. Therewas no correlation between fibrosis grade and values of CAP. None of the patients had values of transaminases higher than 2 times the upper limit value. TE with CAP can be a valuable tool to evaluate hepatic involvement in GD patients, and in this small sample had a good correlation with APRI index. Studies with larger numbers of subjects should be done to confirm this inference.

Aspartate aminotransferase to platelet ratio index as a prospective predictor of hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

APRI (aspartate aminotransferase [AST] to platelet ratio index) is widely used to assess fibrosis and cirrhosis risk, especially in hepatitis C virus (HCV)-infected patients. Few studies have evaluated APRI and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk. Prospective evidence is needed to assess whether APRI predicts HCC risk in HBV patients. In a prospectively enrolled clinical cohort of 855 HBV patients with a 1-year exclusion window (followed for > 1 year and did not develop HCC within 1 year), the predictive value of APRI in HCC risk was evaluated by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. Higher APRI prospectively conferred a significantly increased risk of HCC in univariate analysis (quartile analysis, P trend = 2.9 × 10(-7) ). This effect remained highly significant after adjusting for common host characteristics but not cirrhosis (P trend = 7.1 × 10(-5) ), and attenuated when cirrhosis is adjusted (P trend = 0.021). The effect remained prominent when the analysis was restricted to patients with a more stringent 2-year exclusion window (P trend = 0.008 in quartile analysis adjusting all characteristics including cirrhosis), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Longitudinal comparison demonstrated a persistently higher APRI value in HBV patients who developed HCC during follow-up than those remaining cancer free. APRI might be a marker of HCC risk in HBV patients in cirrhosis-dependent and -independent manners. Further studies are warranted to validate this finding and test its clinical applicability in HCC prevention.

The aspartate aminotransferase to platelet ratio before chemotherapy predicts adverse events for FOLFOX and XELOX regimens including bevacizumab as the first-line therapy for stage IV, recurrent and metastatic colorectal cancer.

Oxaliplatin-based chemotherapy for colorectal liver metastasis can induce hepatotoxicity, which increases the risk of liver resection. We previously reported that the aspartate aminotransferase to platelet ratio (APR) before chemotherapy can indicate oxaliplatin-induced splenomegaly and also predict the occurrence of adverse events during chemotherapy. Bevacizumab (BEV) was recently reported to reduce oxaliplatin-induced splenomegaly. Therefore, the aim of the present study was to investigate whether the APR before chemotherapy can predict the splenomegaly and adverse events associated with FOLFOX/BEV or XELOX/BEV in patients with stage IV or recurrent colorectal cancer. We performed CT volumetry of the spleen before and 12 weeks after FOLFOX/BEV and XELOX/BEV in 63 patients. The incidence of adverse events, haematological parameters, and biochemistry and urinalysis results were assessed during treatment. An increase in the splenic volume was not observed in the FOLFOX/BEV group, but was significant in the XELOX/BEV group (+5.0% vs. +18.8%, P=0.01). The APR before chemotherapy did not indicate the presence of splenomegaly in the 63 patients, however, it did significantly predict the development of grade 2 or higher adverse events during chemotherapy. An APR of 0.15 or higher before chemotherapy did not indicate the presence of splenomegaly, but could predict the development of adverse events due to FOLFOX/BEV and XELOX/BEV treatment.

Noninvasive Serum Fibrosis Markers for Screening and Staging Chronic Hepatitis C Virus Patients in a Large US Cohort

Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease. Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale. We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher. In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.

PMO-163 Fibroscan delineates significant fibrosis better than the King's Fibrosis Score, APRI and FIB4 score when correlated to liver biopsy in a large monocentric cohort of hepatitis C patients

IntroductionIn the context of consideration of antiviral therapy for hepatitis C virus (HCV), fibrosis assessment is critical. An increasing array of non-invasive blood panels are in use; in addition Liver...

Genetically Associated CD16+56− Natural Killer Cell Interferon (IFN)–αR Expression Regulates Signaling and Is Implicated in IFN-α–Induced Hepatitis C Virus Decline

Natural killer (NK) cells likely contribute to outcome of acute hepatitis C virus (HCV) infection and interferon (IFN)-induced control of chronic HCV infection. We previously observed IFN-αR and NKp30 expression associated with IFN-α-dependent NK cell activity. Here, we examined CD16(+)56(-), CD16(+)56(+), and CD16(-)56(+) NK cell subset IFN-αR and NKp30 expression in relation to magnitude of HCV genotype 1 decrease during pegylated IFN-α plus ribavirin therapy. We observed greater baseline IFN-αR and NKp30 expression on CD16(+)56(+) and CD16(-)56(+) NK subsets in HCV-infected patients than in healthy control subjects. Baseline CD16(+)56(-) NK IFN-αR expression was associated with IFN-α-induced pSTAT1, and both were associated with magnitude of HCV decrease during pegylated IFN-α plus ribavirin therapy. Baseline CD16(+)56(-) NK IFN-αR expression was associated with race and interleukin 28B genotype, negatively associated with aspartate aminotransferase-to platelet ratio index, and positively associated with increase in NKp30 expression after in vivo IFN-α exposure. Finally, in vitro IFN-α2a-activated NK cytolysis of HCV-infected target cells was in part dependent on NKp30, and CD16(+)56(-) NK cell IFN-αR expression correlated with cytolytic activity. IFN-αR expression on CD16(+)56(-) NK cells during chronic HCV infection may in part be genetically determined, and level of expression regulates IFN-α signaling, which in turn may contribute to control of HCV infection.

High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients

BackgroundCXCL10 may contribute to the host immune response against the hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral therapy. The aim of our study was to analyze the relationship among virological, immunological, and clinical characteristics with plasma CXCL10 levels in human immunodeficiency virus (HIV)/HCV-coinfected patients. MethodsWe carried out a cross-sectional study on 144 patients. CXCL10 and insulin were measured using an immunoassay kit. The degree of insulin resistance was estimated for each patient using the homeostatic model assessment (HOMA) method. Insulin resistance was defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were calculated. ResultsThe variables associated with log10 CXCL10 levels by univariate analysis were age (b=0.013; p=0.023), prior AIDS-defining condition (b=0.127; p=0.045), detectable plasma HIV viral load (b=0.092; p=0.006), log10 HOMA (b=0.216; p=0.002), HCV-genotype 1 (b=0.114; p=0.071), and liver fibrosis assessed by all non-invasive indexes (log10 APRI (b=0.296; p=0.001), log10 FIB-4 (b=0.436; p<0.001), log10 Forns index (b=0.591; p<0.001), log10 HGM1 (b=0.351; p=0.021), and log10 HGM2 (b=0.215; p=0.018)). However, in multivariate analysis, CXCL10 levels were only associated with HOMA, detectable plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square=0.235; p<0.001). ConclusionPlasma CXCL10 levels were influenced by several characteristics of patients related to HIV and HCV infections, insulin resistance, and liver fibrosis, indicating that CXCL10 may play an important role in the pathogenesis of both HCV and HIV infections.

Comparison of three algorithms of non‐invasive markers of fibrosis in chronic hepatitis C

Preliminary data suggest that performance of non-invasive markers for liver fibrosis in hepatitis C may improve when combined. Three algorithms based on the combination of Fibrotest, Forns' index and AST-to-platelet ratio (APRI) have been proposed: Sequential Algorithm for Fibrosis Evaluation (SAFE biopsy); Fibropaca algorithm; Leroy algorithm. To compare three algorithms to diagnose significant fibrosis (≥ F2 by METAVIR) and cirrhosis (F4). A total of 1013 HCV monoinfected cases undergoing liver biopsy were consecutively enrolled in seven centres. Fibrotest, APRI and Forns' index were measured at the time of liver biopsy, considered the reference standard. Overall, performance of combination algorithms was significantly higher than the single non-invasive methods (P < 0.0001). SAFE biopsy and Fibropaca algorithm saved a significantly higher number of liver biopsies than the single methods (P < 0.0001). For ≥ F2, Fibropaca algorithm saved more biopsies than SAFE biopsy (51.7% vs. 43.8%, P = 0.0003), but with lower accuracy (87.6% vs. 90.3%, P = 0.05). Regarding F4, the number of saved liver biopsies did not differ between SAFE biopsy and Fibropaca algorithm (79.1% vs. 76.2%, P = 0.12). However, SAFE biopsy showed a lower accuracy when compared with Fibropaca algorithm (91.2% vs. 94%, P = 0.02). As to Leroy algorithm, although it showed a good performance for ≥ F2 (93.5% accuracy), it saved less liver biopsies than SAFE biopsy and Fibropaca algorithm (29.2% vs. 43.8% and 51.7% respectively, P < 0.0001). SAFE biopsy and the Fibropaca algorithm have excellent performance for liver fibrosis in hepatitis C, allowing a significant reduction in the need for liver biopsies. They can be useful in clinical practice and for large-scale screening.

Splenomegaly in FOLFOX-naïve stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy

Chemotherapy-associated hepatotoxicity is a common cause of postoperative complications after major hepatectomy. Splenomegaly may indicate portal hypertension due to chemotherapy. To identify chemotherapy-naïve patients with liver damage, the splenic volume (SV) and aspartate aminotransferase to platelet ratio (APR) were investigated. Seventy-one patients receiving FOLFIRI, FOLFOX, or FOLFOX plus bevacizumab as first-line chemotherapy were included in this study. The SV measurement was performed by helical computed tomography volumetry, and the SV index (SVI) was calculated during 6 cycles of chemotherapy. The APR was used as an indicator of liver injury and the APR index (APRI) was calculated. The SVI and APRI were significantly higher in the FOLFOX group than in the FOLFIRI group. In the FOLFOX group, the maximum APR during FOLFOX administration was significantly higher in the subjects with SVI ≥ +30% than in those with SVI < +30% (p < 0.01). The incidences of grade 3 or 4 adverse events and grade 2 or greater histopathological sinusoidal injury were significantly higher in the SVI ≥ +30% than in the SVI < +30% group. Interestingly, the SVI was significantly higher in the group with APR ≥ 0.17 before FOLFOX than in the subjects with an APR < 0.17 before FOLFOX (p < 0.05). Splenomegaly due to FOLFOX-associated hepatotoxicity can be predicted if the APR before FOLFOX is 0.17 or higher.

Use of the aspartate aminotransferase to platelet ratio index to follow liver fibrosis progression in infants with short gut

Background Infants with parenteral nutrition dependence may develop liver dysfunction and progress to liver failure requiring transplantation. The aspartate aminotransferase–to-platelet ratio index (APRI) has good correlation with liver fibrosis progression in adults. This study applies APRI scoring to parenteral nutrition-dependant, short-gut infants to determine hepatic fibrosis progression. Methods Laboratory values and biopsies were collected from initial intestinal resection (time 0) up to transplantation (end). Fibrosis scoring ranged from F0 (normal) to F4 (cirrhosis). Children were divided into 3 groups: (1) isolated intestine; and combined liver/intestine with gestational age (2) 34 weeks or greater and (3) 30 weeks or less. Liver function values over time, including calculated APRI, were analyzed as predictors of fibrosis. Results Fifteen children who had 33 biopsies were included. Median APRI by fibrosis grade was F ≤ 2: 1.88, F3: 3.23, and F4: 14.16 ( P < .01). Median APRI at transplant by study group was (1) isolated intestine: 2.47, (2) liver/intestine 35 weeks or longer EGA: 14.16, and (3) liver/intestine 30 weeks or less EGA: 14.74 ( P = .04). Conclusion Progression of APRI up to 60 days initially demonstrates similar values among study groups, but over time the score distinguishes those children with impending liver cirrhosis and differentiates fibrosis grade and study group.

Diagnostic accuracy of biochemical markers of fibrosis in black African patients with chronic hepatitis B

Contradictory results of the accuracy of bio-chemical markers to predict the stage of fibrosis in black African patients with chronic hepatitis B (CHB) were previously published. We con-ducted a prospective cohort study to determine the diagnostic accuracy of aspartate ami-notransferase to platelet ratio (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AAR), platelet count, age-platelet (AP) in-dex, and FIB-4 index for the prediction of sig-nificant fibrosis or cirrhosis in 117 black African patients (median age: 38 years, males: 73 %) with CHB not previously treated. Among them, 45 had significant fibrosis and 18 had cirrhosis using the METAVIR score system. Factors as-sociated either with significant fibrosis or cir-rhosis were determined in logistic multivariate analysis. Areas under receiver operating curve were assessed and compared for APRI, AAR, AP index, FIB-4 index and platelet count. Sensitivity, specificity, positive and negative predictive values were determined for each biochemical markers. Multivariate analysis showed that as-partate aminotransferase (p 1.1) and FIB-4 index (cut-off > 2.1) ruled out significant fibrosis with high specific-ity of 84.7 % and 86.1 % respectively and nega-tive predictive values of 78.2 % and 72.9 % re-spectively. More accurately, APRI (cut-off > 0.63) or FIB-4 index (cut-off > 1.26) ruled out cirrhosis with high sensitivity of 94.4% and 88.9% and high negative predictive values of 98.1% and 96.3% respectively. In conclusion, APRI and FIB-4 index are simple readily available markers to exclude significant fibrosis or more accu-rately cirrhosis in black African patients with CHB.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus‐coinfected patients via a new noninvasive index: the HGM‐3 index

Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

A prospective study comparing two algorithms that combine non-invasive methods for liver fibrosis in chronic hepatitis C

Background and aim. Numerous non-invasive markers of liver fibrosis have been described but their clinical implementation is still a matter of controversy. Recent studies indicate that their performance may improve when combined. Two algorithms have been proposed to stage liver fibrosis in hepatitis C, combining either fibroscan and fibrotest (Castera's algorithm, gastroenterology 2005) or fibrotest and AST-to-platelet ratio (APRI) (sequential algorithm for fibrosis evaluation, SAFE biopsy, J Hepatol 2006).

Liver Fibrosis: Noninvasive Assessment with MR Elastography versus Aspartate Aminotransferase–to-Platelet Ratio Index

To prospectively compare the sensitivity and specificity of magnetic resonance (MR) elastography with those of the routinely available aspartate aminotransferase-to-platelet ratio index (APRI) test for staging hepatic fibrosis in patients who have undergone liver biopsy for suspicion of chronic liver disease, with histopathologic examination as the reference standard. The study was approved by the ethics committee. All patients gave written informed consent. Eighty-eight patients (37 men, 51 women; mean age, 54.0 years +/- 13.1 [standard deviation]) who underwent liver biopsy for suspicion of chronic liver disease underwent MR elastography and APRI testing within 2 days after liver biopsy. At histopathologic examination, the fibrosis stage was assessed according to METAVIR scores (fibrosis scores F0 [no fibrosis] to F4 [cirrhosis]). MR elastography was performed by transmitting mechanical waves within the liver and measuring the small cyclic displacement of the liver spins with a phase-contrast spin-echo sequence. The performances of MR elastography and APRI testing were assessed, and the optimal cutoff values for fibrosis stage were determined with receiver operating characteristic (ROC) curve analysis. At MR elastography, areas under the ROC curves (A(z)) for elasticity and viscosity, respectively, were 0.999 and 0.863 at fibrosis scores greater than or equal to F2, 0.997 and 0.962 at scores greater than or equal to F3, and 1.000 and 0.986 at score F4. A(z) values for elasticity at MR were significantly larger than those for the APRI (0.854 at scores > or = F2, P < .001; 0.886 at scores > or = F3, P = .003; and 0.851 at score F4, P = .004). Optimal cutoff values of elasticity were 2.5 kPa for fibrosis scores greater than or equal to F2, 3.1 kPa for scores greater than or equal to F3, and 4.3 kPa for score F4. Large A(z) values for elasticity (>0.990 for scores > or = F2, > or = F3, and F4) show that MR elastography was accurate in liver fibrosis staging and superior to biochemical testing with APRIs.

Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

To assess the performance of several non-invasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F > or = 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB). One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 +/- 11.3) with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio (APRI), Fornso index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index (GUCI), Hui's model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC). PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibrotest had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76, respectively). Stepwise combination algorithms of APRI, Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

Prediction of hepatic fibrosis in HIV/HCV co-infected patients using serum fibrosis markers: The SHASTA index

To examine if serum fibrosis biomarkers could accurately identify the stage of liver disease amongst hepatitis C (HCV) and HIV co-infected patients. One hundred and thirty seven HIV/HCV co-infected persons were randomly selected from the Johns Hopkins HIV Clinic cohort. Ninety five had complete testing for fibrosis markers in sera collected at the time of liver biopsy. Biopsies were scored according to Ishak modified histological activity index (F0 no fibrosis to F6 cirrhosis). Fibrosis was evaluated against alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST to platelet ratio (APRI), albumin, total bilirubin, hyaluronic acid (HA) and YKL-40. Sixty nine (73%) had no or minimal portal fibrosis (F0-2) and were compared with remaining subjects (F3-6). Fibrosis scores > or =F3 were found 27 times more often in persons with HA levels >86 ng/ml and 5.5 times more often in persons with HA levels 41-86 ng/ml. Less substantial associations were detected with levels of albumin <3.5 g/dl (OR 4.85) and AST >60 iu (OR 5.91). All 35 subjects who had favorable results of HA, albumin, and AST had minimal fibrosis (F0-2). Amongst HIV/HCV co-infected patients, serum testing for HA, albumin, and AST (SHASTA Index) was able to accurately stage mild and advanced fibrosis.