***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : Transient elastography ( FibroScan ) is a new , non-invasive , rapid , and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness . In cirrhotic patients , liver stiffness measurements range from 12.5 to 75.5 kPa . However , the clinical relevance of these values is unknown . The aim of this prospect i ve study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease . Methods : A total of 711 patients with chronic liver disease were studied . Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection , alcohol , non-alcoholic steatohepatitis , other , or a combination of the above aetiologies . Liver fibrosis was evaluated according to the METAVIR score . Results : Stiffness was significantly correlated with fibrosis stage ( r = 0.73 , p<0.0001 ) . Areas under the receiver operating characteristic curve ( 95 % confidence interval ) were 0.80 ( 0.75–0.84 ) for patients with significant fibrosis ( F>2 ) , 0.90 ( 0.86–0.93 ) for patients with severe fibrosis ( F3 ) , and 0.96 ( 0.94–0.98 ) for patients with cirrhosis . Using a cut off value of 17.6 kPa , patients with cirrhosis were detected with a positive predictive value and a negative predictive value ( NPV ) of 90 % . Liver stiffness was significantly correlated with clinical , biological , and morphological parameters of liver disease . With an NPV > 90 % , the cut off values for the presence of oesophageal varices stage 2/3 , cirrhosis Child-Pugh B or C , past history of ascites , hepatocellular carcinoma , and oesophageal bleeding were 27.5 , 37.5 , 49.1 , 53.7 , and 62.7 kPa , respectively . Conclusion : Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease . Its use for the follow up and management of these patients could be of great interest and should be evaluated further BACKGROUND Liver biopsy is thought m and atory for management of patients with hepatitis C virus ( HCV ) infection , especially for staging fibrosis . We aim ed , in our prospect i ve study , to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinical ly significant fibrosis ( including early stages ) . METHODS We assessed  liver-biopsy patients with detectable HCV by PCR , for eligibility , and took a  blood sample on the day of the procedure . The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients . We devised a fibrosis index that included the most informative markers ( combined with age and sex ) for the first-year group . 11 serum markers were assessed as well as fibrosis stage : F0=no fibrosis and F1=portal fibrosis ; and for clinical ly significant fibrosis , F2=few septa , F3=many septa , and F4=cirrhosis . Statistical analysis was by logistic regression , neural connection , and receiver-operating characteristic ( ROC ) curves . FINDINGS First-year and second-year patient-group characteristics and biochemical markers did not differ . The overall frequency of clinical ly significant fibrosis was 40 % ( 138 patients ) . The most informative markers were : alpha2 macroglobulin , alpha2 globulin ( or haptoglobin ) , gamma globulin , apolipoprotein A1 , gamma glutamyltranspeptidase , and total bilirubin . The areas ( SD ) under the ROC curves for the first-year ( 0.836 [ 0.430 ] ) and second-year groups ( 0.870 [ 0.340 ] ) did not differ ( p=0.44 ) . With the best index , a high negative predictive value ( 100 % certainty of absence of F2 , F3 , or F4 ) was obtained for scores ranging from zero to 0.10 ( 12 % [ 41 ] of all patients ) , and high positive predictive value ( > 90 % certainty of presence of F2 , F3 , or F4 ) for scores ranging from 0.60 to 1.00 ( 34 % [ 115 ] of all patients ) . INTERPRETATION A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis . Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study . The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0 , no fibrosis , to F4 , cirrhosis . MR elastography was performed by transmitting low-frequency ( 65 Hz ) mechanical waves into the liver with a transducer placed at the back of the patients . The MR pulse sequence was a motion-sensitized spin-echo sequence , phase-locked to the mechanical excitation . The phase maps were processed to obtain shear elasticity and shear viscosity maps . The mean hepatic shear elasticity increased with increasing stage of fibrosis . The mean elasticity was 2.24 + /- 0.23 kPa in the 11 patients without substantial fibrosis ( F0-F1 grade s ) , 2.56 + /- 0.24 kPa in the four patients with substantial fibrosis ( F2-F3 ) and 4.68 + /- 1.61 kPa in the 10 patients with cirrhosis ( F4 ) . The differences between groups were statistically significant ( p < or= 0.05 ) . The mean shear viscosity was significantly higher in the patients with cirrhosis ( 5.19 + /- 1.85 Pa x s ) than in the patients without cirrhosis ( 2.39 + /- 0.86 Pa x s in F0-F1 and 2.27 + /- 0.38 Pa x s in F2-F3 patients ) . It is concluded that non-invasive MR elastography is a feasible method to assess the stage of liver fibrosis PURPOSE To prospect ively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . Forty patients and 25 healthy volunteers were examined . Subjects fasted , a bolus of SonoVue ( 0.6 mL ) was injected into a cubital fossa vein , and hepatic venous time-intensity profiles were measured with spectral Doppler tracing . This was repeated with two injections of Levovist ( 2 g ) and another injection of SonoVue .  Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed . A sustained signal intensity increase of 10 % above baseline levels indicated hepatic vein transit time ( HVTT ) . Carotid artery audio intensity was measured in volunteers . Analysis of variance and t tests were used for statistical analysis . RESULTS Twelve patients had mild hepatitis ; 18 , moderate or severe hepatitis ; and 10 , cirrhosis .  Mean HVTTs in control , mild hepatitis , moderate or severe hepatitis , and cirrhosis groups were 38.3 seconds + /- 2.4 ( st and ard error ) , 47.5 seconds + /- 6.5 , 29.5 seconds + /- 10.8 , and 17.6 seconds + /- 5.0 , respectively , with Levovist ( P < .001 ) and 29.4 seconds + /- 6.9 , 27.4 seconds + /- 9.3 , 22.9 seconds + /- 4.7 , and 16.4 seconds + /- 4.9 , respectively , with SonoVue ( P < .001 ) . HVTT decreased as severity increased at imaging with both contrast agents . There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue ; however , there were significant differences in HVTT between all patient groups with Levovist .  HVTT of SonoVue was shorter than that of Levovist in all groups ( P < .001 ) except the cirrhosis group ; in this group , HVTT of the two contrast agents was similar ( P = .05 ) . No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist ( 9.1 seconds + /- 2.4 [ st and ard error ] and 8.4 seconds + /- 2.5 , respectively , P = .18 ) . CONCLUSION HVTT was significantly shorter with SonoVue than with Levovist ; there was no significant difference in  cardiopulmonary transit time AIM To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C ( CHC ) . METHODS Two hundred and thirty-seven patients with CHC were included in this study . Liver biopsy was performed under ultrasonography on 217 of the patients , excluding twenty with clear clinical evidence of liver cirrhosis . Fifty subjects without liver disease were enrolled as a control group ( stage 0 ) . Twenty-five patients with sustained virological response ( SVR ) to interferon ( IFN ) therapy were also enrolled . These patients underwent liver biopsy before IFN therapy .  Examination of liver stiffness ( LS ) was performed by elastography . RESULTS Medians ( 50 % levels ) of LS were 4.1 ( 3.5 - 4.9 ) , 6.3 ( 4.8 - 8.5 ) , 8.8 ( 6.8 - 12.0 ) , 14.6 ( 10.5 - 18.6 ) , and 22.2 ( 15.4 - 28.0 ) , respectively , in the fibrosis stages 0 - 4 ( P < 0.001 ) . LS was significantly correlated with four serum fibrosis markers . LS values in patients with SVR were 3.8 ( 3.5 - 5.6 ) , 5.2 ( 4.4 - 6.8 ) , 6.8 ( 6.1 - 7.6 ) , and 6.1 ( 3.6 - 7.9 ) , respectively , in the fibrosis stages 1 - 4 . In all stages , LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy . LS was significantly correlated with serum concentrations of hyaluronic acid , type IV collagen , type IV collagen 7S , and type III procollagen N peptide . CONCLUSION LS correlated well with the histological stage of fibrosis . Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography The course of hepatitis C virus ( HCV ) infection carriers with normal/near-normal aminotransferases ( NALT ) is usually mild ; however , in a few , fibrosis progression occurs . We aim ed to verify whether monitoring by liver biopsy might be replaced by noninvasive methods and to identify factors associated with fibrosis progression in patients with persistently normal alanine aminotransferases . We studied 40 untreated HCV-RNA-positive subjects ( 22 male ; median age , 44 years ) , who underwent two liver biopsies , with a median interval of 78.5 months , during which alanine aminotransferase concentrations ( median number of determinations : 12 ) never exceeded 1.2 times the upper normal limit . Within 9 months from the second biopsy , they were tested by the shear elasticity probe ( Fibroscan ) and the artificial intelligence algorithm FibroTest .  METAVIR fibrosis scores were analyzed in relationship to demographic , clinical , and viral parameters . Weighted kappa analysis was used to verify whether the results of noninvasive methods agreed with histology . Significant fibrosis ( > or = F2 ) , present at the first biopsy in only one patient ( 2.5 % ) , was observed at the second biopsy in 14 patients ( 35 % ) . At multivariate analysis , excess alcohol consumption in the past ( > 20 g/d ; P = .017 ) and viral load ( > 8.0 x 10(6 ) copies/mL ; P = .021 ) were independent predictors of progression . In identifying patients with significant fibrosis , inter-rater agreement was excellent for Fibroscan ( weighted kappa = 1.0 ) , and poor for FibroTest ( weighted kappa = -0.041 ) . In conclusion , among HCV carriers with NALT , Fibroscan is superior to the FibroTest in the noninvasive identification of fibrosis , for which excess alcohol consumption in the past and high viral load represent risk factors The risk of complications from percutaneous liver biopsy is low , but discomfort is common and complications require hospitalization in approximately 4 % of patients . The optimal method of performing these biopsies is unknown . The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle .  Between 1992 and 1994 , 836 patients were 
    Output:
    
Although no single non-invasive test or model developed to date can match that information obtained from actual histology ( i.e. inflammation , fibrosis , steatosis ) , combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis , and thereby avoid liver biopsy in a significant percentage of patients