Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients

Background

The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility.

Objectives

The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment.

Patients and Method

A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard.

Results

Significant fibrosis (F ≥ 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F ≥ 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis.

Conclusions

The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage.     

Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C

BACKGROUND/AIMS: Non-invasive markers of liver fibrosis have recently been developed as an alternative to liver biopsy. The aim of this study was to compare the diagnostic performance of 6 scores (MP3, Fibrotest, Fibrometer, Hepascore, Forns' score and APRI). METHODS: We studied 180 chronic hepatitis C patients. Liver fibrosis was staged according to the METAVIR scoring system. RESULTS: Overall diagnostic performance of scores determined by AUROCs ranged from 0.86 for Fibrometer to 0.78 for Forns' score (NS) for discriminating F0F1 versus F2F3F4. For discriminating F0F1F2 versus F3F4, AUROCs ranged from 0.91 for Fibrometer to 0.78 for Forns' score (p<0.02). Significant or extensive fibrosis was predicted in 10-86% of patients with positive predictive value (PPV) ranging from 55% to 94%. Using logistic regression, statistical independence was demonstrated for MP3, Fibrotest and APRI. Diagnostic performance of paired-combination scores was then evaluated. The best combinations could select one-third of patients for whom either absence of significant fibrosis or presence of extensive fibrosis could be predicted with more than 90% of certainty. CONCLUSIONS: Current non-invasive scores give reliable information on liver fibrosis in one-third of chronic hepatitis C patients, especially when used in combination.     

Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C

BACKGROUND/AIMS: We evaluated the test performance profile (TPP) of blood tests of liver fibrosis. METHODS: Three hundred and fifty-six patients with C chronic hepatitis were included in two centers. Metavir staging of liver specimens by two independent pathologists and the following tests were evaluated: Fibrotest (FT), APRI, FibroMeter (FM), and Hepascore (HS). RESULTS: Metavir stages were: F0: 4%, F1: 55%, F2: 26%, F3: 11%, and F4: 4%. The AUROCs were not significantly different, respectively, FT, FM, APRI, HS: >or=F2: 0.79, 0.78, 0.76, >or=0.76; F3: 0.81, 0.85, 0.81, 0.81; and F4: 0.86, 0.94, 0.92, 0.89. The TPP relies on the paired comparison of blood-test misclassification based on liver specimen, e.g. FT vs FM, respectively: F0+1: 18 vs 28% (p=0.0003), >or=F2: 43 vs 31% (p=0.004). There was no center effect. CONCLUSIONS: In those populations, the four blood tests had a similar performance for significant fibrosis (F>or=2), lying in the lower range of published results which is attributable to a low >or=F2 prevalence, and for >or=F3 and F4. However, FM and FT had performance profiles significantly different as a function of fibrosis stages or diagnostic target (fibrosis cut-off). This has to be considered during the interpretation process. Moreover, the performance should be reported with different diagnostic targets.     

Non‐invasive biomarkers of liver fibrosis in haemophilia patients with hepatitis C: can you avoid liver biopsy?

Liver biopsy remains the gold standard for the evaluation of fibrosis despite its risks and limitations, especially in haemophilia patients. Recently, non-invasive biomarkers have been used to assess histological features. The most thoroughly evaluated biomarker is the FibroTest (FT) (AUROC 0.80 for fibrosis stages F2F3F4 vs. F0F1). To estimate liver fibrosis in haemophilia patients infected with hepatitis C (HCV) using non-invasive biomarkers without liver biopsy. One hundred and thirty-two haemophilia patients (124 male, mean age 38 +/- 14 years) with anti-HCV antibodies were evaluated. These patients were stratified into several groups: patients with features of advanced liver disease - seven, persistently HCV RNA-negative - 21, persistently normal liver function tests (LFTs)- 24, HCV/HIV co-infected - 27. The following biomarkers of fibrosis were used: FT, AST-to-platelet ratio index (APRI), Forns index, age-platelet index and hyaluronic acid. The obtained scores were correlated with the clinical features of the patients. Estimated by the FT, the distribution of the stage of fibrosis in the 132 patients was F0F1 = 65% (86/132), F2 = 5% (7/132), F3 = 13% (17/132) and F4 = 17% (22/132). Using FT, all patients with clinical suspicion of advanced liver disease were classified as F3F4, whereas patients with persistently HCV RNA-negative were all classified as F0F1. Twenty-one per cent (5/24) of the patients with persistently normal LFTs had fibrosis stage F3F4. The proportion of F3F4 among HCV/HIV co-infected patients was significantly higher than among HCV mono-infected (52% vs. 33%; P = 0.05). Concordance of three or more biomarkers was present in 43% (57/132) of the patients. Liver biopsy could be avoided in 70% (92/132) using a practical assumption that if FT is in concordance with APRI and/or Forns, then we may confidently rely on the biomarker. Concordance rate for patients with presumably advanced or minimal liver disease was excellent (100% and 95% respectively). In our HCV-infected haemophilia patients, FT correctly identified clinically advanced or minimal liver disease. Discordance among the various biomarkers of fibrosis was considerate; nevertheless, practical combination of FT, APRI, and Forns may predict stage of fibrosis with accuracy, potentially avoiding liver biopsy in the majority of the patients.     

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

AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.
METHODS： 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）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, 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）.
RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest 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 APR1, 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.
CONCLUSION： 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.     

Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of ...     

Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).     

Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C

BACKGROUND/AIMS: In chronic hepatitis C, biopsy is the gold standard for assessment of liver fibrosis. Non-invasive markers have been proposed but their use is limited by diagnostic accuracy. Our aim was to increase the diagnostic performance of non-invasive markers of liver fibrosis by combining them in sequential algorithms. METHODS: One hundred and ninety patients with chronic hepatitis C were evaluated for AST to platelets ratio (APRI), Forns' index and Fibrotest at the time of liver biopsy and stepwise combination algorithms were developed and validated prospectively in 100 additional patients. RESULTS: Three algorithms were developed: (1) significant fibrosis (F>or=2 by METAVIR) was identified with high diagnostic performance (>94% accuracy) using APRI as screening test, followed by Fibrotest in APRI non-classified cases and restricting liver biopsy to patients classified F0-F1 by non-invasive tests. (2) A slightly modified algorithm had similar performance when applied to hepatitis C carriers with normal ALT. (3) Identification of cirrhosis (95% accuracy) was achieved using a dedicated algorithm with different cut-off, reducing by 60-70% the liver biopsies needed. CONCLUSIONS: Stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic hepatitis C. Need for liver biopsy is reduced by 50-70% but cannot be completely avoided.     

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

BACKGROUND/AIMS: To examine if serum fibrosis biomarkers could accurately identify the stage of liver disease amongst hepatitis C (HCV) and HIV co-infected patients. METHODS: 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. RESULTS: 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). CONCLUSIONS: Amongst HIV/HCV co-infected patients, serum testing for HA, albumin, and AST (SHASTA Index) was able to accurately stage mild and advanced fibrosis.     

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co‐infection

Aim: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. Patients and Methods: This retrospective cross‐sectional study included consecutive patients with HIV/HCV co‐infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). Results: One hundred and eleven patients were included (73% men, mean age 40.2±7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774±0.045. An APRI≥1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index <0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (≥0.6 and <1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. Conclusion: APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co‐infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.     

Comparison of noninvasive models of fibrosis in chronic hepatitis B

Background and goals

Liver fibrosis influences treatment and surveillance strategies in chronic hepatitis B (CHB). This multicenter study aimed to examine the accuracy of serum fibrosis models in CHB patients including those with low alanine aminotransferase (ALT) levels and serially in those undergoing treatment.

Method

We examined noninvasive fibrosis models [Hepascore, Fibrotest, APRI, hepatitis e antigen (HBeAg)-positive and -negative models] in 179 CHB patients who underwent liver biopsy and fibrosis assessment by METAVIR and image morphometry. Serial Hepascore measurements were assessed in 40 subjects for up to 8.7?years.

Results

Hepascore was more accurate than Fibrotest [area under the curve (AUC) 0.83 vs. 0.72, P?=?0.05] and HBeAg-positive model (AUC 0.83 vs. 72, P?=?0.03) for significant fibrosis but was not significantly different to APRI or HBeAg-negative scores. Fibrosis area assessed by morphometry was correlated with Hepascore (r?=?0.603, P?<?0.001), Fibrotest (r?=?0.392, P?=?0.03), and HBeAg-positive (r?=?0.492, P?=?0.001) scores only. Among 73 patients with an ALT <60?IU/L, noninvasive models were useful to predict fibrosis (PPV 80?C90%) or exclude significant fibrosis (NPV 79?C100%). Hepascore increased significantly among patients monitored without treatment and reduced among patients undergoing therapy (0.05/year?±?0.03 vs. ?0.04/year?±?0.02, P?=?0.007).

Conclusions

Serum fibrosis models are predictive of fibrosis in CHB and assist in identifying subjects with low?Cnormal ALT levels for treatment.     

Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C: the fibropaca study

OBJECTIVES: Fibrotest (FT) and Actitest (AT) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus (HCV). The aim of this study was to perform an external validation of FT and AT and to study the discordances between FT/AT and liver biopsy in patients with chronic hepatitis C. METHODS: A total of 519 consecutive patients with chronic HCV were prospectively included in five centers, with liver biopsy and biochemical markers taken at the same day. Fifteen patients were excluded because their biopsies could not be interpreted. Diagnostic accuracies were assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: Median biopsy size was 15 mm (range: 2-58), with 9 portal tracts (1-37) and 1 fragment (1-12). 46% (230/504) were classified F2-F4 in fibrosis and 39% A2-A3 in activity. FT area under ROC curve for diagnosis of activity (A2-A3), significant fibrosis (F2-F4), and severe fibrosis (F3-F4) were 0.73 [0.69-0.77], 0.79 [0.75-0.82], and 0.80 [0.76-0.83], respectively. Among the 92 patients (18%) with 2 fibrosis stages of discordance between FT and biopsy, the discordance was attributable to FT in 5% of cases, to biopsy in 4%, and undetermined in 9%. CONCLUSIONS: This prospective independent and multicenter study confirms the diagnostic value of FT and AT found in the princeps study and suggests that FT and AT can be an alternative to biopsy in most patients with chronic HCV.     

Liver fibrosis markers in alcoholic liver disease

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.     

A novel panel of blood markers to assess the degree of liver fibrosis

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, alpha2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P = .01), 0.820 for the Forns test (P = .005), and 0.794 for the APRI test (P < 10(-4)). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, gamma-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 ((a)R(2) = 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets ((a)R(2) = 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis.     

Évaluation non invasive de la fibrose hépatique au cours des co-infections VIH et VHC et/ou VHB

Liver fibrosis must be evaluated during the diagnosis and follow-up of patients with chronic hepatitis. This evaluation is usually based on the histological analysis of liver biopsies, but in recent years, noninvasive methods have been developed to assess liver fibrosis, including various blood tests and FibroScan®. Blood tests use a combination of biological markers and are effective to diagnose liver fibrosis. APRI and FibroTest® have both demonstrated accuracy in HIV/HCV coinfected patients similar to that in monoinfected HCV patients. FibroMètre®, FibroTest® and Hepascore have similar AUROC measurements, which are higher than those produced by APRI in HIV/HCV coinfected and HBV patients. Measuring liver stiffness (FibroScan®) is an accurate method for the diagnosis of cirrhosis. It is simple to perform but costly.     

Routine Laboratory Blood Tests May Diagnose Significant Fibrosis in Liver Transplant Recipients with Chronic Hepatitis C: A 10 Year Experience

Background and Aims: The aims of our study were to determine whether routine blood tests, the aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) and Fibrosis 4 (Fib-4) scores, were associated with advanced fibrosis and to create a novel model in liver transplant recipients with chronic hepatitis C virus (HCV). Methods: We performed a cross sectional study of patients at The University of California at Los Angeles (UCLA) Medical Center who underwent liver transplantation for HCV. We used linear mixed effects models to analyze association between fibrosis severity and individual biochemical markers and mixed effects logistic regression to construct diagnostic models for advanced fibrosis (METAVIR F3-4). Cross-validation was used to estimate a receiving operator characteristic (ROC) curve for the prediction models and to estimate the area under the curve (AUC). Results: The mean (± standard deviation [SD]) age of our cohort was 55 (±7.7) years, and almost three quarter were male. The mean (±SD) time from transplant to liver biopsy was 19.9 (±17.1) months. The mean (±SD) APRI and Fib-4 scores were 3 (±12) and 7 (±14), respectively. Increased fibrosis was associated with lower platelet count and alanine aminotransferase (ALT) values and higher total bilirubin and Fib-4 scores. We developed a model that takes into account age, gender, platelet count, ALT, and total bilirubin, and this model outperformed APRI and Fib-4 with an AUC of 0.68 (p < 0.001). Conclusions: Our novel prediction model diagnosed the presence of advanced fibrosis more reliably than APRI and Fib-4 scores. This noninvasive calculation may be used clinically to identify liver transplant recipients with HCV with significant liver damage.     

Improving estimation of liver fibrosis using combination and newer noninvasive biomarker scoring systems in hepatitis C-infected haemophilia patients

Non-invasive biomarkers have gained popularity for estimating fibrosis stage. In our hepatitis C-infected haemophilia patients, Fibrotest (FT) correctly identified clinically advanced or minimal liver disease. More accurate tests, like the FibroMeters, have recently been validated. The aim of the study was to improve the estimation of liver fibrosis in hepatitis C-infected haemophiliacs using a combination of biomarkers and FibroMeters. One hundred and thirty-two hepatitis C-infected haemophilia patients (124 male, mean age: 39+/-14 years) were evaluated. The following biomarkers were used: FT, AST-to-platelet ratio index (APRI), Forns index, hyaluronic acid and FibroMeter. We applied a published algorithm suggesting that if FT is in concordance with APRI and/or Forns score, then the FT concurs with liver biopsy for estimation of fibrosis. Concordance of three or more biomarkers was present in 43.2% (57/132) of the patients. This high discordance rate was mainly because of indeterminate scores. Significant fibrosis (F2-F4) was estimated at 34.8% (46/132) and 37.9% (50/132) by the FT and FibroMeter respectively. The discordance rate between the FT and FibroMeter was 16.7% (22/132), (P<0.01 vs. other biomarkers). Using the algorithm, liver histology could be confidently estimated in 69.7% (92/132) of the patients. Concordance between the FT and FibroMeter in those patients who met the terms of the algorithm was 90.2% (83/92). Discordance between biomarkers is significant, and is mainly because of biomarkers with indeterminate results. The concordance rate between FT and FibroMeter is higher compared with the other biomarkers. Practical combination of tests may potentially limit the need of liver biopsy in the majority of haemophilia patients.     

Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis

The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to update the 2007 meta-analysis to systematically assess the accuracy of APRI in predicting significant fibrosis, severe fibrosis, and cirrhosis stage in hepatitis C virus (HCV) monoinfected and HCV / human immunodeficiency virus (HIV) coinfected individuals. Studies comparing APRI versus biopsy in HCV patients were identified via a thorough literature search. Areas under summary receiver operating characteristic curves (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to examine the APRI accuracy for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis. Heterogeneity was explored using meta-regression. Twenty-one additional studies were eligible for the update and, in total, 40 studies were included in this review (n = 8,739). The summary AUROC of the APRI for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis were 0.77, 0.80, and 0.83, respectively. For significant fibrosis, an APRI threshold of 0.7 was 77% sensitive and 72% specific. For severe fibrosis, a threshold of 1.0 was 61% sensitive and 64% specific. For cirrhosis, a threshold of 1.0 was 76% sensitive and 72% specific. Moreover, we found that the APRI was less accurate for the identification of significant fibrosis, severe fibrosis, and cirrhosis in HIV/HCV coinfected patients. CONCLUSION: Our large meta-analysis suggests that APRI can identify hepatitis C-related fibrosis with a moderate degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among chronic hepatitis C patients.     

Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients

BACKGROUND: The impact of immune reconstitution on liver fibrosis in HIV/hepatitis C virus (HCV) patients is unknown. In this case-control study, we investigated the impact of HIV infection on the severity of liver fibrosis and identified related factors. METHODS: We studied 116 HIV/HCV patients and 235 HCV only patients all untreated for HCV. Each co-infected patient was matched with two singly-infected patients according to gender, age at contamination and duration of infection. Liver biopsy was analysed using the METAVIR score. RESULTS: Alcohol consumption and route of contamination differed between HCV-infected and HCV/HIV co-infected patients. Among co-infected patients, a F3-F4 Metavir score was significantly more frequent than in mono-infected patients. Co-infected patients with severe fibrosis (F3-F4) had higher transaminase, ferritin levels and lower CD4 T-cell count than patients with none to moderate fibrosis (F0-F2). Although median duration of treatment with nucleoside analogues, non-nucleoside analogues and protease inhibitors were comparable in both groups, the delay between the presumed date of contamination and treatment initiation with highly active antiretroviral therapy (HAART) was significantly longer for patients with severe fibrosis than those with none to moderate fibrosis. Finally, the mean rate of fibrosis progression was significantly slower among patients exposed to HAART. CONCLUSION: Early antiretroviral therapy in co-infected HIV-HCV patients may slow liver fibrosis progression.     

Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine

BACKGROUND: The hepatotoxicity of highly active antiretroviral therapy (HAART) could enhance liver fibrosis in HIV/Hepatitis C virus (HCV)-coinfected patients. Moreover, HAART-related immune restoration could lessen HCV-associated liver damage. The data on the effect of protease inhibitors (PI) on liver fibrosis are scant and contradictory. No information is available on the relationship between non-nucleoside analogue therapy and liver fibrosis in co-infected patients. OBJECTIVE: To investigate the associations between the use of different antiretroviral drugs and the liver fibrosis in patients with HIV and HCV infections. DESIGN: Cross-sectional study. METHODS: All HIV/HCV co-infected patients with an available liver biopsy and known or estimated duration of HCV infection seen at a Infectious Diseases Unit were included in the study. The fibrosis stage and the fibrosis progression rate were evaluated. RESULTS: The inclusion criteria were fulfilled by 152 patients. Age at HCV infection < 20 years [adjusted odds ratio (AOR), 0.39; 95% confidence interval (CI), 0.19-0.82], PI-based HAART (AOR, 0.39; 95% CI, 0.19-0.78) and nevirapine-based HAART (AOR, 2.56; 95% CI, 1.02-6.58) were associated with fibrosis stage >or= F3. The variables associated with fibrosis progression rate > 0.2 units/year were age at HCV infection < 20 years (AOR, 0.23; 95% CI, 0.1-0.52), CD4 cell counts < or = 250 x 10/l at liver biopsy (AOR, 2.8; 95% CI, 1.1-7.1), PI-based HAART (AOR, 0.39; 95% CI, 0.2-0.8) and nevirapine-based HAART (AOR, 3.82; 95% CI, 1.9-7.6). CONCLUSIONS: HAART regimens including nevirapine are associated with faster liver fibrosis progression in HIV-infected patients with chronic hepatitis C. In contrast, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.