[Show abstract][Hide abstract] ABSTRACT: Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation.
[Show abstract][Hide abstract] ABSTRACT: Background: The criteria for defining failure to control bleeding in cirrhotic patients were introduced at the Baveno II/III meetings and were widely used as endpoints in clinical trials. Because they lacked specificity, the Baveno IV criteria were proposed in 2005 and slightly modified in 2010 (Baveno V). These criteria included a new index for patients undergoing transfusion, called adjusted-blood-requirement-index (ABRI= number of blood units/(final-initial hematocrit + 0.01)), with a cut-off value of 0.75. In this multicenter prospective study, we sought to (1) validate the Baveno IV/V criteria; (2) compare them to the Baveno II/III criteria; (3) assess ABRI performance using a standardized calculation.Methods: The key inclusion criteria were: (1) variceal bleeding; (2) cirrhosis; (3) no need to modify the transfusion policy. The patients were classified according to the Baveno IV, V, and II/III criteria. The gold standard for failure during a 5-day period was the clinical judgment of 3 independent experts, blinded to the Baveno assessments.Results: A total of 249 patients were included. The experts’ agreement in clinical judgment of the failure was 80%. Failure occurred in 20.5% of patients; the c-statistics were 0.72 vs. 0.64 and 0.65 for Baveno IV vs. Baveno II/III and Baveno V criteria (p=0.001 for both). ABRI did not improve the diagnostic performance of the Baveno IV criteria. The Baveno IV, but not Baveno II/III, criteria independently predicted survival.Conclusion: The Baveno IV criteria demonstrated a higher accuracy than the Baveno II/III and Baveno V criteria for assessing failure to control bleeding and predicted survival independently. Together, our results show that ABRI is not a useful metric, and the Baveno IV criteria should replace the Baveno II/III criteria. (Hepatology 2014;)
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis C virus (HCV) infection is characterized by progressive hepatic fibrosis, a process dependent on monocyte recruitment and accumulation into the liver. The mediators expressed in chronically injured liver that control the differentiation of human monocytes into pro-fibrotic macrophages (Mφ), remain poorly defined. We report that chronically HCV-infected patients with high fibrosis stages have higher serum levels of M-CSF and IL-34 than HCV-infected patients with lower fibrosis stages and healthy subjects. Immunohistochemistry reveals an intense expression of IL-34 and M-CSF by hepatocytes around liver lesions. In addition, HCV infection and inflammatory cytokines enhance the in vitro production of IL-34 and M-CSF by hepatocytes. We next analyzed the acquisition of pro-fibrotic properties by Mφ generated with M-CSF (M-CSF-Mφ) or IL-34 (IL-34-Mφ). M-CSF and IL-34 upregulate the expression, by differentiating monocytes, of CCL2, CCL4, CCR1 and CCR5 which are involved in monocyte recruitment/Mφ accumulation in liver lesions. M-CSF-Mφ and IL-34-Mφ also express the hepatic stellate cell (HSC) activators, PDGF, TGF-φ and galectin-3. IL-34-Mφ and M-CSF-Mφ induce type I collagen synthesis by HSC, the main collagen-producing cells in liver fibrosis. IL-13, which expression correlates with the fibrosis stage in HCV-infected patients, decreases the expression of the collagenase MMP-1 by IL-34-Mφ and M-CSF-Mφ, thereby enhancing collagen synthesis. By inhibiting the production of IFN-φ by activated NK cells, IL-34-Mφ and M-CSF-Mφ prevent the IFN-φ-induced killing of HSC. Collectively, these results identify M-CSF and IL-34 as potent pro-fibrotic factors in HCV liver fibrosis. (Hepatology 2014;)
[Show abstract][Hide abstract] ABSTRACT: Elastometry is more accurate than blood tests for cirrhosis diagnosis. However, blood tests were developed for significant fibrosis, with the exception of CirrhoMeter developed for cirrhosis. We compared the performance of Fibroscan and CirrhoMeter, and classic binary cirrhosis diagnosis versus new fibrosis staging for cirrhosis diagnosis.
The diagnostic population included 679 patients with hepatitis C and liver biopsy (Metavir staging and morphometry), Fibroscan, and CirrhoMeter. The prognostic population included 1110 patients with chronic liver disease and both tests.
Binary diagnosis: AUROCs for cirrhosis were: Fibroscan: 0.905; CirrhoMeter: 0.857; and P=0.041. Accuracy (Youden cutoff) was: Fibroscan: 85.4%; CirrhoMeter: 79.2%; and P<0.001. Fibrosis classification provided 6 classes (F0/1, F1/2, F2±1, F3±1, F3/4, and F4). Accuracy was: Fibroscan: 88.2%; CirrhoMeter: 88.8%; and P=0.77. A simplified fibrosis classification comprised 3 categories: discrete (F1±1), moderate (F2±1), and severe (F3/4) fibrosis. Using this simplified classification, CirrhoMeter predicted survival better than Fibroscan (respectively, χ=37.9 and 19.7 by log-rank test), but both predicted it well (P<0.001 by log-rank test). Comparison: binary diagnosis versus fibrosis classification, respectively, overall accuracy: CirrhoMeter: 79.2% versus 88.8% (P<0.001); Fibroscan: 85.4% versus 88.2% (P=0.127); positive predictive value for cirrhosis by Fibroscan: Youden cutoff (11.1 kPa): 49.1% versus cutoffs of F3/4 (17.6 kPa): 67.6% and F4 classes (25.7 kPa): 82.4%.
Fibroscan's usual binary cutoffs for cirrhosis diagnosis are not sufficiently accurate. Fibrosis classification should be preferred over binary diagnosis. A cirrhosis-specific blood test markedly attenuates the accuracy deficit for cirrhosis diagnosis of usual blood tests versus transient elastometry, and may offer better prognostication.
Journal of clinical gastroenterology 05/2014; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy.AimTo compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC).MethodsA total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy).ResultsDuring the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751–0.868)] with a significant increase for FIB4: 0.879 [0.832–0.919] (P = 0.002), FibroMeter: 0.870 [0.812–0.922] (P = 0.005) and APRI: 0.861 [0.813–0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses.Conclusions
Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis.
[Show abstract][Hide abstract] ABSTRACT: Introduction: No data are available about the prediction of long-term survival using repeated non-invasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), APRI, and FIB-4 evolution in CHC. Patients and methods: CHC patients with two LSM (1000-1500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. Results: 1025 patients were included. Median follow-up after fLSM was 38.0 months (IQR: 27.7-46.1) during which 35 patients died (14 liver-related death) and 7 had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (p≥0.24) whereas FIB-4 provided more accurate prognostic models than APRI (p=0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and SVR. Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with increase (≥1 kPa/year) in 7-14 kPa bLSM, or decrease (≤0 kPa/year) in ≥14 kPa bLSM (p=0.949 between these two groups). Patients with increase (>0 kPa/year) in ≥14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significant different prognosis. Conclusion: Three-year evolution of non-invasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. (Hepatology 2014;).
[Show abstract][Hide abstract] ABSTRACT: Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal-bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal-bridging and perisinusoidal fibrosis, whereas portal-bridging area was predominant in cirrhosis. Measurement of portal-bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal-bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal-bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal-bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal-bridging fibrosis area (first step, P<0.001), the steatosis area (second step, P<0.001), and the Metavir A grade (third step, P=0.001), but not to the perisinusoidal fibrosis area. Automated quantification in a large cohort of chronic hepatitis C showed that perisinusoidal fibrosis progressively grew in early fibrosis stages but did not increase in septal or cirrhotic stages and that the portal-bridging fibrosis area appeared as a more accurate tool to assess fibrosis progression than the whole fibrosis area.Modern Pathology advance online publication, 3 January 2014; doi:10.1038/modpathol.2013.225.
[Show abstract][Hide abstract] ABSTRACT: Background
Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology.
650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis.
The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic.
A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.
Journal of Gastroenterology 01/2014; · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination.
All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584 patients.
The most accurate combination was provided by using most markers of FibroMeter and Fibroscan result targeted for significant fibrosis, i.e., "E-FibroMeter". Its classification accuracy (91.7%) and precision (assessed by F difference with Metavir: 0.62±0.57) were better than those of FibroMeter (84.1%, p<0.001; 0.72±0.57, p<0.001), Fibroscan (88.2%, p=0.011; 0.68±0.57, p=0.020), and a previous CSF-SF classification of FibroMeter + Fibroscan (86.7%, p<0.001; 0.65±0.57, p=0.044). The accuracy for fibrosis absence (F0) was increased, e.g., from 16.0% with Fibroscan to 75.0% with E-FibroMeter (p<0.001). Cirrhosis sensitivity was improved, e.g., E-FibroMeter: 92.7% vs. Fibroscan: 83.3%, p=0.004. The combination improved reliability by deleting unreliable results (accuracy <50%) observed with a single test (1.2% of patients) and increasing optimal reliability (accuracy ≥85%) from 80.4% of patients with Fibroscan (accuracy: 90.9%) to 94.2% of patients with E-FibroMeter (accuracy: 92.9%), p<0.001. The patient rate with 100% predictive values for cirrhosis by the best combination was twice (36.2%) that of the best single test (FibroMeter: 16.2%, p<0.001).
the new test combination increased: accuracy, globally and especially in patients without fibrosis, staging precision, cirrhosis prediction, and even reliability, thus offering improved fibrosis staging. This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 09/2013; · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity.
Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions.
Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion.
In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion.
Critical care (London, England) 07/2013; 17(4):R139. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of death by cancer worldwide. The prognosis of patients with metastatic HCC remains limited, with an expected median survival lower than 50% at 1year. Here, we report the case of a 63-year-old man who suffered from a small HCC in the liver and a large unique metastasis in the right adrenal gland. A surgical resection of both lesions was performed. Seven months later, HCC recurred with an isolated right renal metastatic lymphadenopathy and a high alpha-fetoprotein level. HCC was brought under control by sorafenib; the alpha-fetoprotein level was greatly reduced but remained moderately elevated and stable over 2years after the onset of chemotherapy. Additional external radiotherapy on the metastatic lymphadenopathy led to a normalization of the alpha-fetoprotein level and discontinuation of sorafenib treatment. One year after the end of radiotherapy, a second isolated metastasis occurred in the right lung. This tumor was surgically removed. Twenty-one months after this second surgical procedure, i.e., more than 5.5years after the initial diagnosis of metastatic HCC, the patient was asymptomatic and tumor free.
Gastroentérologie Clinique et Biologique 04/2013; · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.
[Show abstract][Hide abstract] ABSTRACT: Objective
The aspartate aminotransferase activity (AST)/alanine aminotransferase activity (ALT) ratio is used as liver fibrosis index whereas the reported data are conflicting. In chronic hepatitis C (CHC), reported diagnostic accuracies range from none to good for significant fibrosis and to excellent for cirrhosis. Assuming that AST/ALT increases are mainly due to vitamin B6 defects since pyridoxal phosphate (PLP), active form of B6, acts as coenzyme in transamination reactions, we evaluated the diagnostic accuracy of the AST/ALT ratio using standardized methods for AST and ALT activities, with PLP addition as recommended, in a prospective multicenter cohort of CHC patients.
ALT and AST activities were measured using the recommended IFCC methods with addition of pyridoxal 5’-phosphate. We evaluated the AST/ALT ratio for the diagnosis of liver fibrosis or cirrhosis in a cohort of CHC patients included in a multicenter prospective study. A liver biopsy was performed in each patient and reviewed by two independent pathologists in order to determine the fibrosis stage according to Metavir classification which was the reference standard.
AST/ALT ratio significantly increased with histological stage of liver fibrosis and there was a significant correlation between Metavir fibrosis stage and AST/ALT ratio (r = 0.129, P < 0.0035). The ROC curve analyses showed that the AST/ALT ratio does not discriminate significant fibrosis (F ≥ 2) (AUROC = 0.531) and had only very poor diagnostic accuracies for severe fibrosis (F ≥ 3) (AUROC = 0.584) or cirrhosis (F4) (AUROC = 0.626).
AST/ALT ratio is not a good and discriminative index of liver fibrosis in CHC when aminotransferase activities are determinate according to the international recommendations.
Gastroentérologie Clinique et Biologique 01/2013; 37(5):467–472. · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: With the obesity burden, non-alcoholic fatty liver disease (NAFLD) is present in 20 - 30% of the general population. Few NAFLD patients will develop end-stage liver disease, for which the main predictor is the liver fibrosis stage. It is thus mandatory to evaluate liver fibrosis in NAFLD patients to determine their liver-related prognosis. Areas covered: Here the authors discuss the various options available for liver fibrosis diagnosis in clinical practice in NAFLD patients. At present, liver biopsy remains the reference examination. In the past decade, several non-invasive fibrosis tests, for example, elastography techniques or blood tests, have been developed and evaluated for the diagnosis of liver fibrosis in NAFLD. Their accuracy, advantages and limitations will be discussed. Expert opinion: Liver biopsy, an invasive procedure, is not appropriate for routine fibrosis evaluation and follow-up in the large population of NAFLD patients. Non-invasive fibrosis tests are accurate tools to evaluate liver fibrosis and thus identify at-risk patients for liver-related complications. They represent an exciting research field as further studies are required to definitively validate their diagnostic and prognostic utility.
Expert Opinion on Medical Diagnostics 09/2012; 6(5):381-394.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: =10 valid measurements, ≥60% success rate, and IQR/median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. METHODS: 1165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. RESULTS: 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% vs 81.5% well-classified patients for the diagnosis of cirrhosis (p=0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of =10 valid measurements or LSE success rate. These two reliability criteria determined 3 LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10 <IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and "poorly reliable" (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (p<10(-3) ). According to these new reliability criteria, 9.1% of LSE were "poorly reliable" (versus 24.3% unreliable LSE with the usual definition, p<10(-3) ), 74.3% were "reliable", and 16.6% were "very reliable". CONCLUSION: The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: "very reliable", "reliable", and "poorly reliable" LSE. (HEPATOLOGY 2012.).
[Show abstract][Hide abstract] ABSTRACT: We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage.
Journal of Viral Hepatitis 02/2012; 19(2):e143-53. · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.
OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F ≥ 2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F ≥ 2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.
OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.
PLoS ONE 01/2012; 7(4):e35612. · 3.53 Impact Factor