Non-invasive Markers Of Liver Fibrosis Research Articles

Noninvasive markers of liver fibrosis in Latin America and Mexico

Noninvasive markers of liver fibrosis in Latin America and Mexico

HIV/hepatitis B virus co-infection: current challenges and new strategies

Chronic hepatitis B virus (HBV) infection, which affects 7%-10% of HIV-infected patients, is associated with an increased frequency of AIDS-related and non-AIDS-related clinical endpoints, such as end-stage liver diseases including cirrhosis and hepatocellular carcinoma. Broad access to a very efficient antiviral therapy containing nucleos(t)ide analogues with dual activity against HBV and HIV reverse transcriptases has initiated a transition in the paradigm of HBV control in the context of HIV-induced immunosuppression. The control of viral replication is not currently such a problem, but preventing the emergence of HBV polymerase and surface gene mutants after prolonged exposure to nucleos(t)ides and their consequences in terms of HBV vaccine escape are the next long-term challenges. Another challenge is the prevention of end-stage liver disease in an ageing population, in whom non-invasive markers of liver fibrosis, although used more frequently as a substitute for liver biopsy, are not the panacea. Finally, access to prevention, diagnosis, care and treatment of HBV infection remains a major issue in developing countries, including most regions of Africa and Asia, where HBV is endemic and the epidemic of HIV infection is still thriving.

Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX-3 index

HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR > or = F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 +/- 0.081 (0.909, when adjusted by DANA). Values < or =4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 +/- 0.053 vs 0.762 +/- 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.

The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

BackgroundLiver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD) which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center.MethodsThe study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69%) of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI), which varies between 0 and 10.ResultsThe final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI) with bias correction 0.80 to 0.90) for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0) could be used to rule in liver fibrosis without performing liver biopsy.ConclusionPNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

Reversal of liver fibrosis.

Hepatic fibrosis is a scarring process associated with an increased and altered deposition of extracellular matrix in the liver. It is caused by a variety of stimuli and if fibrosis continues unopposed, it would progress to cirrhosis which poses a significant health problem worldwide. At the cellular and molecular level, this progressive process is characterized by cellular activation of hepatic stellate cells and aberrant activity of transforming growth factor-β with its downstream cellular mediators. Liver biopsy has been the reference test for assessment of hepatic fibrosis, but because of its limitations, noninvasive markers of liver fibrosis were developed. Liver fibrosis or cirrhosis was considered irreversible in the past but progress of research on the molecular pathogenesis of liver fibrosis has shown that hepatic cellular recovery is possible. Currently, no acceptable therapeutic strategies exist, other than removal of the fibrogenic stimulus, to treat this potentially devastating disease.

Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Non-Invasive Markers of Liver Fibrosis in HCV Mono-Infected and in HIV/HCV Co-Infected Subjects

Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. This review describes the role of non-invasive markers in assessing hepatic fibrosis in both HCV mono-infected and HIV/HCV co-infected subjects.

Noninvasive markers of liver fibrosis: playing the probabilities

Noninvasive markers of liver fibrosis: playing the probabilities

Other non-invasive markers of liver fibrosis

An intensive research effort in the field of non-invasive evaluation of liver fibrosis has recently permitted the description and validation of several serum markers of fibrosis, mainly in chronic hepatitis C patients. In addition to the commonly used tests such as FibroTest or FibroMeters, other either indirect (aspartate aminotransferase, prothrombin time, platelets) or direct (PIIINP, hyaluronic acid, metalloproteinases) markers, usually used in combination, have been evaluated. Simple scores such as APRI or FIB-4 have also been widely studied and have revealed interesting, albeit non-comprehensive, data on liver fibrosis, especially in terms of significant, extensive fibrosis or cirrhosis. These simple scores may be proposed as a first-line investigation, bearing in mind their limitations and comparing them with more accurate methods for evaluating liver fibrosis if necessary. Other scores, including direct serum markers, which can be difficult to assess, have given disappointing results that, in general, were either similar to, or only slightly better than, the results of the simpler tests. Further studies are needed to identify new markers that are more accurate and, above all, able to predict the outcome of liver fibrosis.

FibroTest-ActiTest as a non-invasive marker of liver fibrosis

FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC) and subsequently assessed in other frequent liver diseases, including chronic hepatitis B (CHB), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). The primary aim of the present study was to update a previous meta-analysis of FT diagnostic value, and to summarize its advantages and limitations. The secondary aim was to provide an overview of the prognostic value of FT in CHC, CHB and ALD. For diagnostic value, the main endpoint was the FT area under the ROC curves (AUROCs) for the diagnosis of bridging fibrosis (F2/F3/F4 vs F0/F1), standardized for the spectrum of fibrosis. Sensitivity analysis integrated the non-standardized observed AUROCs, the independency of authors, size (length) of biopsy, prospective design, correctness of procedures, co-morbidities, and timelag between biopsy and serum sampling. For prognostic value, the main endpoint was the FT AUROC for the prognostic value of liver complications or death related to liver disease. A total of 38 diagnostic studies were included, which pooled 7985 subjects who had undergone both FT and biopsy (4600 HCV, 1580 HBV, 267 NAFLD, 524 ALD and 1014 mixed). The mean standardized AUROC was 0.84 (95% CI, 0.83-0.86), with no differences in terms of causes of liver disease: HCV 0.84 (0.82-0.87); HBV 0.81 (0.78-0.83); NAFLD 0.84 (0.76-0.92); ALD 0.87 (0.82-0.92); and mixed 0.85 (0.81-0.89). Three prognostic studies were also included. FT was found to have higher or similar prognostic value compared with biopsy in patients with CHC, CHB or ALD. FibroTest is an effective alternative to biopsy in patients with chronic hepatitis C or B, ALD or NAFLD. Indeed, the prognostic performance of FibroTest was at least as accurate as that of biopsy in patients with chronic hepatitis C or B, or ALD.

Combining non-invasive methods for assessment of liver fibrosis

Non-invasive markers of liver fibrosis, including biochemical scores using simple biochemical parameters and transient elastography (TE), have been developed over the past decade to either replace or reduce the need for liver biopsy (LB) in the assessment of liver fibrosis. Although their diagnostic accuracy in liver fibrosis is promising, around 20% of patients are likely to be misclassified if these tests or LB are used alone. However, using a combination of several biochemical scores (Fibropaca algorithm, Leroy algorithm) or one biochemical score with TE (Bordeaux algorithm) will increase diagnostic accuracy for fibrosis and reduce the need for LB. Stepwise combination algorithms of non-invasive scores (SAFE biopsy) also improve the diagnostic performance in chronic hepatitis C (CHC) compared with the use of a single non-invasive score. Other sequential stepwise algorithms have been developed in CHC with similar performance results. Comparisons of different combinations of non-invasive methods indicate that the SAFE biopsy, Fibropaca algorithm and Bordeaux algorithm are excellent and comparable in the non-invasive diagnosis of liver fibrosis in HCV patients, and will markedly reduce the need for LB. They may also be useful in clinical practice and particularly for large-scale screening of HCV patients.

Large-scale multicentre comparison of three algorithms combining serum non-invasive markers for liver fibrosis in chronic hepatitis C

Background. Non-invasive serum markers have been proposed as surrogate of liver fibrosis, but their diagnostic accuracy is not such to substitute liver biopsy. Recent data suggest that their performance may improve when combined. Three algorithms based on combination of Fibrotest, Forns’index and/or AST-to-platelet ratio (APRI) have been proposed with the strategy to reduce rather than completely avoid liver biopsy (sequential algorithm for fibrosis evaluation; safe biopsy; fibropaca algorithm; Leroy algorithm).

Serum levels of YKL‐40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is highly prevalent among end-stage renal disease (ESRD) patients undergoing haemodialysis and it is an important cause of morbidity and mortality in this population. The aim of this study was to evaluate the diagnostic value of YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in 185 ESRD HCV-infected patients. Significant liver fibrosis was defined as METAVIR F2, F3 or F4 stages. Significant fibrosis was observed in 45 patients (24%). By univariate analysis, higher levels of YKL-40, HA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as well as reduced platelet count were associated with fibrosis. However, by multivariate analysis, only AST (P = 0.001), platelet count (P = 0.004) and HA (P = 0.042) were independently associated with significant fibrosis. For the prediction of significant fibrosis, the areas under receiver operating characterictic curve (AUROC) of the regression model (0.798) was significantly higher than the AUROC of YKL-40 (0.607) and HA (0.650). No difference was noted between the AUROC of the regression model and AST to platelet ratio index (APRI) (0.787). Values <8.38 of the regression model showed a negative predictive value of 94% and scores >or=9.6 exhibited a positive predictive value of 65%. If biopsy indication was restricted to scores in the intermediate range of the regression model, it could have been correctly avoided in 61% of the cases. In conclusion, APRI and a model based on AST, platelet count and HA showed better accuracy than YKL-40 and HA (when used solely) for the prediction of significant fibrosis in ESRD HCV-infected patients.

Non‐invasive markers for the prediction of fibrosis in chronic hepatitis C infection

Liver fibrosis occurs as a result of chronic liver injury and is the hallmark of chronic liver disease. The final stage of progressive liver fibrosis is cirrhosis, which is implicated in portal hypertension, end-stage liver disease and hepatocellular carcinoma. Liver biopsy has historically been the gold standard test for the assessment of liver fibrosis for liver diseases such as viral hepatitis, autoimmune hepatitis and primary biliary cirrhosis. Improved serological tests have enhanced the diagnosis of these conditions and reduced the need for liver biopsy. Liver biopsy is unpopular among patients and clinicians. It is associated with morbidity and mortality, and in addition is subject to sampling error, inter- and intra-observer variability. There is therefore a need for non-invasive markers of liver fibrosis that are accurate, reliable, cheap and easy to use. The aim of this review is to examine the different non-invasive methods that can be used to estimate the severity of fibrosis. The methods evaluated include clinical examination, routine laboratory investigations, imaging tests, specialized tests of liver function and finally serum extra-cellular matrix markers of fibrosis. The review mainly focuses on fibrogenesis in the context of chronic hepatitis C infection.

Diagnosis and Quantitation of Fibrosis

Hepatic fibrosis is the final common pathway for many different liver insults. Originally considered to be irreversible, hepatic fibrosis is now known to be a dynamic process with a significant potential for resolution. The diagnosis and quantitation of fibrosis have traditionally relied on liver biopsy. However, there are a number of drawbacks including the invasive nature of the procedure, sampling error, and interobserver variability. This article reviews the current role of liver biopsy in the assessment of hepatic fibrosis and discusses the role of the newer noninvasive methods including serum markers and radiologic tests.

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).

Performance of noninvasive markers for liver fibrosis is reduced in chronic hepatitis C with normal transaminases

Journal of Viral HepatitisVolume 15, Issue 6 p. 474-474 Performance of noninvasive markers for liver fibrosis is reduced in chronic hepatitis C with normal transaminases G. Sebastiani, G. Sebastiani Venetian Institute of Molecular Medicine (VIMM), Padova, Italy Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this authorA. Vario, A. Vario Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this authorM. Guido, M. Guido Department of Oncological and Surgical Sciences, University of Padova, Padova, ItalySearch for more papers by this authorA. Alberti, A. Alberti Venetian Institute of Molecular Medicine (VIMM), Padova, Italy Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this author G. Sebastiani, G. Sebastiani Venetian Institute of Molecular Medicine (VIMM), Padova, Italy Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this authorA. Vario, A. Vario Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this authorM. Guido, M. Guido Department of Oncological and Surgical Sciences, University of Padova, Padova, ItalySearch for more papers by this authorA. Alberti, A. Alberti Venetian Institute of Molecular Medicine (VIMM), Padova, Italy Department of Clinical and Experimental Medicine, University of Padova, Padova, ItalySearch for more papers by this author First published: 06 April 2008 https://doi.org/10.1111/j.1365-2893.2008.00987.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume15, Issue6June 2008Pages 474-474 RelatedInformation

Magnetic Resonance Elastography for the Noninvasive Staging of Liver Fibrosis

The purpose of our study was to prospectively compare the success rate and diagnostic accuracy of magnetic resonance elastography, ultrasound elastography, and aspartate aminotransferase to platelets ratio index (APRI) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease. We performed a prospective blind comparison of magnetic resonance elastography, ultrasound elastography, and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital. Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference. A total of 141 patients were assessed. The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography (133/141 [94%] vs 118/141 [84%]; P = .016). Magnetic and ultrasound elastography, APRI measurements, and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients. The areas under the receiver operating characteristic curves of magnetic resonance elasticity (0.994 for F >or= 2; 0.985 for F >or= 3; 0.998 for F = 4) were larger (P < .05) than those of ultrasound elasticity, APRI, and the combination of ultrasound elasticity and APRI (0.837, 0.709, and 0.849 for F >or= 2; 0.906, 0.816, and 0.936 for F >or= 3; 0.930, 0.820, and 0.944 for F = 4, respectively). Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis.

Diagnostic Accuracy of Serum Hyaluronic Acid, FIBROSpect II, and YKL-40 for Discriminating Fibrosis Stages in Chronic Hepatitis C

Noninvasive serum markers of liver fibrosis are being used as an alternative to liver biopsy. Currently available tests distinguish, with accuracy, only absent/minimal fibrosis (Ishak stages 0-1) and advanced fibrosis/cirrhosis (Ishak stages 4-6), but not intermediate fibrosis (Ishak stages 2-3). Our aim was to evaluate the diagnostic accuracy of hyaluronic acid (HA), FIBROSpect II (FS-II), and YKL-40 (chondrex, human cartilage glycoprotein-39) in various clinically important categories of fibrosis, and further correlate these serum markers with digital quantification of fibrosis (DQF) and Ishak stages. Serum HA, YKL-40, and FS-II were retrospectively assessed and correlated with Ishak stages and DQF scores in 75 patients with chronic hepatitis C (HCV). Spearman's rho statistics assessed relationships among all parameters, and receiver operator characteristic curves evaluated accuracy of each parameter when compared to the Ishak stages. All three serum markers and DQF correlated highly with one another (P < or = 0.01) and with Ishak stages of fibrosis. Among the serum markers, HA was effective in discriminating between Ishak stages 0-1 and Ishak stages 2-3 compared with FS-II, with an area under the curve of 0.76 versus 0.66 and a false-positive rate of 0.33 versus 0.67, respectively. All three serum markers predicted advanced fibrosis and cirrhosis. YKL-40 had the highest false-positive rates in all categories of fibrosis. HA can be utilized as a reliable surrogate marker in distinguishing three clinically relevant stages of fibrosis: absent/minimal, intermediate, and advanced/cirrhosis. HA should be considered as a cost-effective alternative to other serum markers for staging fibrosis and for determining the timing and selection of HCV treatment.

Effect of Antiviral Treatment on Serum Markers of Liver Fibrosis in HIV–Hepatitis C virus-Coinfected Patients: The Fibrovic 2 Study – ANRS HC02

Non-invasive liver fibrosis scores have been proposed as alternatives to liver biopsy (LB) in hepatitis C virus (HCV)-infected patients. Here, we aimed to assess the effect of antiviral treatment on non-invasive serological markers of liver fibrosis in HIV-HCV-coinfected patients. We included 114 HIV-HCV-coinfected patients with LBs performed before and 6 months after the end of treatment (week 72; W72). Fibrotest, the Forn's index, age-platelet ratio index, SHASTA, FIB-4, Hepa-score and Fibrometer scores were assessed. There were 29 (25%) patients who achieved sustained virological response (SVR). At baseline (BL), all non-invasive fibrosis scores except the Forn's index did not show significantly lower values in SVR patients. At W72, all non-invasive scores, except Hepascore, showed a significant decrease in SVR patients (P<0.01). There was a significant difference in fibrosis stages on LBs between BL and W72 in SVR and non-SVR patients. In HIV-HCV-coinfected patients, HCV clearance is associated with a significant reduction in non-invasive fibrosis serological markers, which most likely reflect the histological improvement associated with SVR. If confirmed, such results will reinforce the reliability of these markers in the follow-up after HCV treatment.