Transient elastography and diffusion-weighted magnetic resonance imaging for assessment of liver fibrosis in children with chronic hepatitis C

BACKGROUND Chronic hepatitis C(CHC)is a health burden with consequent morbidity and mortality.Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment.Noninvasive altern-atives for liver biopsy such as transient elastography(TE)and diffusion-weighted magnetic resonance imaging(DW-MRI)are critical needs.AIM To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.METHODS This prospective cross-sectional study initially recruited 100 children with CHC virus infection.Sixty-four children completed the full set of investigations including liver stiffness measurement(LSM)using TE and measurement of apparent diffusion coefficient(ADC)of the liver and spleen using DW-MRI.Liver biopsies were evaluated for fibrosis using Ishak scoring system.LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters.RESULTS Most patients had moderate fibrosis(73.5%)while 26.5%had mild fibrosis.None had severe fibrosis or cirrhosis.The majority(68.8%)had mild activity,while only 7.8%had moderate activity.Ishak scores had a significant direct correlation with LSM(P=0.008)and were negatively correlated with both liver and spleen ADC but with no statistical significance(P=0.086 and P=0.145,respectively).Similarly,histopatho-logical activity correlated significantly with LSM(P=0.002)but not with liver or spleen ADC(P=0.84 and 0.98 respectively).LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages(area under the curve=0.700 and 0.747,respectively)with a better performance of liver ADC.CONCLUSION TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

Transient elastography(Fibro Scan~?) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease- Where do we stand?

Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis(laboratory tests and ultrasonography) or cannot be applied as a screening procedure(liver biopsy). Among the non-invasive tests, transient elastography(Fibro Scan?, TE) with controlled attenuation parameter(CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

Factors associated with significant liver fibrosis assessed using transient elastography in general population

AIM: To investigate the prevalence of significant liver fibrosis assessed using transient elastography(TE) and its predictors in asymptomatic general population.METHODS: A total of 159 subjects without chronic viral hepatitis who underwent comprehensive medical health check-up between January 2012 and July 2012 were prospectively recruited. Significant liver fibrosis was defined as liver stiffness value > 7.0 k Pa.RESULTS: The mean age and body mass index(BMI) of the study population(men 54.7%) was 56.0 years and 24.3 kg/m2. Among the study subjects, 11(6.9%) showed significant liver fibrosis. On univariate analysis, BMI, alanine aminotransferase(ALT), homeostasis model assessment of insulin resistance, carotid intimal media thickness(IMT), number of calcified plaques on carotid ultrasound, and visceral fat area on computed tomography were significantly higher in subjects with significant liver fibrosis than in those without(all P < 0.05). However, on multivariate analysis, BMI [odds ratio(OR) =1.487; P = 0.045], ALT(OR = 1.078; P = 0.014), carotid IMT(OR = 3.244; P = 0.027), and the number of calcified carotid plaques(OR = 1.787; P = 0.031) were independent predictors of significant liver fibrosis. CONCLUSION: The prevalence of significant liver fibrosis assessed using TE was 6.9% in apparently healthy subjects. High BMI, high ALT, thicker carotid IMT, and higher numbers of calcified carotid plaqueswere independently associated with the presence of significant liver fibrosis.

Diagnostic accuracy of transient elastography (Fibro Scan) in detection of esophageal varices in patients with cirrhosis: A meta-analysis

AIM To investigate the diagnostic accuracy of Fibro Scan(FS) in detecting esophageal varices(EV) in cirrhotic patients.METHODS Through a systemic literature search of multiple databases, we reviewed 15 studies using endoscopy as a reference standard, with the data necessary to calculate pooled sensitivity(SEN) and specificity(SPE), positive and negative LR, diagnostic odds ratio(DOR) and area under receiver operating characteristics(AUROC). The quality of the studies was rated by the Quality Assessment of Diagnostic Accuracy studies-2 tool. Clinical utility of FS for EV was evaluated by a Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis. All statistical analyses were conducted via Stata12.0, MetaD isc1.4 and RevM an5.RESULTS In 15 studies(n = 2697), FS detected the presence of EV with the summary sensitivities of 84%(95%CI: 81.0%-86.0%), specificities of 62%(95%CI: 58.0%-66.0%), a positive LR of 2.3(95%CI: 1.81-2.94), a negative LR of 0.26(95%CI: 0.19-0.35), a DOR of 9.33(95%CI: 5.84-14.92) and an AUROC of 0.8262. FS diagnosed the presence of large EV with the pooled SEN of 0.78(95%CI: 75.0%-81.0%), SPE of 0.76(95%CI: 73.0%-78.0%), a positive and negative LR of 3.03(95%CI: 2.38-3.86) and 0.30(95%CI: 0.23-0.39) respectively, a summary diagnostic OR of 10.69(95%CI: 6.81-16.78), and an AUROC of 0.8321. A meta-regression and subgroup analysis indicated different etiology could serve as a potential source of heterogeneity in the diagnosis of the presence of EV group. A Deek's funnel plot suggested a low probability for publication bias.CONCLUSION Using FS to measure liver stiffness cannot provide high accuracy for the size of EV due to the various cutoff and different etiologies. These limitations preclude widespread use in clinical practice at this time; therefore, the results should be interpreted cautiously given its SEN and SPE.

Correlation of transient elastography with hepatic venous pressure gradient in patients with cirrhotic portal hypertension: A study of 326 patients from India

AIMTo study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension.METHODSThis retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman&#x02019;s correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index.RESULTSThe study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P &#x0003c; 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P &#x0003c; 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%.CONCLUSIONTE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%.

Transient elastography improves detection of liver cirrhosis compared to routine screening tests

AIM:To investigate the diagnostic significance oftransient elastography(TE) in a daily routine clinical setting in comparison to clinical signs,laboratory parameters and ultrasound.METHODS:TE,ultrasound,laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine.RESULTS:Sensitivity of TE for the detection of liver cirrhosis was 90.4%,compared to 80.1% for ultrasound,58.0% for platelet count and 45.1% for cutaneous liver signs(P < 0.0001 for comparisons with histology).AUROC for TE was 0.760(95%CI:0.694-0.825).Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825(95%CI:0.768-0.882).TE correlated with laboratory parameters of cirrhosis progression like albumin(r =-0.43),prothrombin time(r =-0.44),and bilirubin(r = 0.34; P < 0.001 for each).Particularly,in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1%(P < 0.04) and 16.3%(P < 0.02),respectively.CONCLUSION:Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

AIM: To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases.METHODS: A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected.RESULTS: The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P &#x0003c; 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 &#x000b1; 7.23 kPa) compared to Wilson disease (8.30 &#x000b1; 0.84 kPa) and HCV groups (7.43 &#x000b1; 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable associated with higher LSM (P &#x0003c; 0.0001).CONCLUSION: TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.

Diagnostic role of transient elastography in patients with autoimmune liver diseases:A systematic review and meta-analysis

BACKGROUND Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy.However,previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease.The diagnostic value of transient elastography for autoimmune liver diseases(AILDs)is worth studying.AIM To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.METHODS The PubMed,Cochrane Library and EMBASE databases were searched.Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs[autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)and primary sclerosing cholangitis(PSC)]were included.The summary area under the receiver operating characteristic curve(AUROC),diagnostic odds ratio,sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.RESULTS A total of 60 articles were included in this study,and the number of patients with AIH,PBC and PSC was 1594,3126 and 501,respectively.The summary AUROC of transient elastography in the diagnosis of significant fibrosis,advanced fibrosis and cirrhosis in patients with AIH were 0.84,0.88 and 0.90,respectively,while those in patients with PBC were 0.93,0.93 and 0.91,respectively.The AUROC of cirrhosis for patients with PSC was 0.95.However,other noninvasive indices(aspartate aminotransferase to platelet ratio index,aspartate aminotransferase/alanine aminotransferase ratio,fibrosis-4 index)had corresponding AUROCs less than 0.80.CONCLUSION Transient elastography exerts better diagnostic accuracy in AILD patients,especially in PBC patients.The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

To scan or not to scan:Use of transient elastography in an integrated health system

BACKGROUND Non-invasive tests,such as Fibrosis-4 index and transient elastography(com-monly FibroScan),are utilized in clinical pathways to risk stratify and diagnose non-alcoholic fatty liver disease(NAFLD).In 2018,a clinical decision support tool(CDST)was implemented to guide primary care providers(PCPs)on use of FibroScan for NAFLD.AIM To analyze how this CDST impacted health care utilization and patient outcomes.METHODS We performed a retrospective review of adults who had FibroScan for NAFLD indication from January 2015 to December 2017(pre-CDST)or January 2018 to December 2020(post-CDST).Outcomes included FibroScan result,laboratory tests,imaging studies,specialty referral,patient morbidity and mortality.RESULTS We identified 958 patients who had FibroScan,115 before and 843 after the CDST was implemented.The percentage of FibroScans ordered by PCPs increased from 33%to 67.1%.The percentage of patients diagnosed with early F1 fibrosis,on a scale from F0 to F4,increased from 7.8%to 14.2%.Those diagnosed with ad-vanced F4 fibrosis decreased from 28.7%to 16.5%.There were fewer laboratory tests,imaging studies and biopsy after the CDST was implemented.Though there were more specialty referrals placed after the CDST was implemented,multivariate analysis revealed that healthcare utilization aligned with fibrosis score,whereby patients with more advanced disease had more referrals.Very few patients were hospitalized or died.CONCLUSION This CDST empowered PCPs to diagnose and manage patients with NAFLD with appropriate allocation of care towards patients with more advanced disease.

Performance of liver stiffness measurements by transient elastography in chronic hepatitis

AIM:To compare results of liver stiffness measurements by transient elastography(TE) obtained in our patients population with that used in a recently published meta-analysis.METHODS:This was a single center cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled.TE was carried out by using FibroScan(Echosens,Paris,France).Liver biopsy was performed on the same day as TE,as day case procedure.Fibrosis was staged according to the Metavir scoring system.The diagnostic performance of TE was assessed by using receiver operating characteristic(ROC) curves and the area under the ROC curve analysis.RESULTS:Two hundred and fifty-two patients met the inclusion criteria.Six(2%) patients were excluded due to unreliable TE measurements.Thus,246(171 men and 75 women) patients were analyzed.One hundred and ninety-five(79.3%) patients had chronic hepatitis C,41(16.7%) had chronic hepatitis B,and 10(4.0%) were coinfected with human immunodeficiency virus.ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa forF ≥ 2;7.9 kPa forF ≥ 3;9.6 kPa for F = 4 in all patients(n = 246),and as high as 6.9 kPa for F ≥ 2;7.3 kPa for F ≥ 3;9.3 kPa for F = 4 in patients with hepatitis C(n = 195).Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2;9.6 kPa for F ≥ 3;12.2 kPa for F = 4 in all patients(n = 246),and as high as 7.0 kPa forF ≥ 2;9.3 kPa forF ≥ 3;12.3 kPa forF = 4 in patients with hepatitis C(n = 195).CONCLUSION:The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.

Effect of alcohol consumption on liver stiffness measured by transient elastography

AIM:To determine the evolution of transient elastography(TE) in patients with alcoholic liver disease according to alcohol cessation or continuation.METHODS:We retrospectively selected in our local database all patients who had two TE between June 2005 and November 2010 with chronic alcohol excessive consumption and excluded those with associated cause of liver disease.TE was performed at least one week apart by senior operator.TE examinations with less than ten successful measures or with an interquartile range above 30% were excluded.We retrospectively reviewed file of all patients to include only patient followed up by trained addictologist and for which definite information on alcohol consumption was available.Concomitant biological parameters [aspartate amino transferase(AST),alanine amino transferase and gamma-glutamyl transpeptidase(GGT)] within 4 wk of initial and final TE were recorded.Putative fibrosis score according to initial and final TE were determined with available cut-off for alcoholic liver disease and hepatitis C.Initial and final putative fibrosis score were compared according to alcohol consumption during follow-up.RESULTS:During the study period 572 patients had TE examination for alcoholic liver disease and 79 of them had at least two examinations.Thirty-seven patients met our criteria with a median follow-up of 32.5 wk.At the end of the study,13(35%) were abstinent,and 24(65%) relapsers.Eight patients had liver biopsy during follow-up.TE decreased significantly during follow-up in 85% of abstinent patients [median(range):-4.9(-6.1,-1.9)],leading to a modification of the putative fibrosis stage in 28%-71% of patient according to different cut-off value.In relapsers TE increased in 45% and decreased in 54% of patient.There was no statistical difference between initial and final TE in relapsers.In the overall population,using 22.6 kPa as cut-off for cirrhosis,4 patients had cirrhosis at initial TE and 3 patients had cirrhosis at final TE.Using 19.5 kPa as cut-off for cirrhosis,7 patients had cirrhosis at initial TE and 5 patients had cirrhosis at final TE.Using 12.5 kPa as cut-off for cirrhosis,16 patients had cirrhosis at initial TE and 15 patients had cirrhosis at final TE.Evolution of biological data was in accordance with the relapse or abstinent status:abstinence ratio(duration of abstinence/duration follow-up) was correlated with AST ratio(r =-0.465,P = 0.007) and GGT ratio(r =-0.662,P<0.0001).GGT was correlated with initial(r = 0.488,P = 0.002) and final TE(r = 0.49,P<0.005).Final TE was correlated with AST(r = 0.362,P<0.05).Correlation between TE ratio and AST ratio(r = 0.44,P = 0.01) revealed that TE varied proportionally to AST for all patients irrespective of their alcohol status.The same relationship was observed between TE ratio and GGT ratio(r = 0.65,P<0.0001).Evolution of TE was significantly correlated with the ratio of time of abstinence to observation time(r =-0.387,P = 0.016) and the evolution of liver enzymes.CONCLUSION:TE significantly decreased with abstinence.Results of TE in alcoholic liver disease cannot be interpreted without taking into account alcohol consumption and liver enzymes.

Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.

Performance of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome

AIM To investigate the performance of transient elastography(TE) for diagnosis of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis(AIHPBC) overlap syndrome.METHODS A total of 70 patients with biopsy-proven AIH-PBC overlap syndrome were included. Spearman correlation test was used to analyze the correlation of liver stiffness measurement(LSM) and fibrosis stage. Independent samples Student's t-test or one-way analysis of variance was used to compare quantitative variables. Receiver operating characteristics(ROC) curve was used to calculate the optimal cut-off values of LSM for predicting individual fibrosis stages. A comparison on the diagnostic accuracy for severe fibrosis was made between LSM and other serological scores.RESULTS Patients with AIH-PBC overlap syndrome had higher median LSM than healthy controls(11.3 ± 6.4 k Pa vs 4.3 ± 1.4 k Pa, P < 0.01). LSM was significantly correlated with fibrosis stage(r = 0.756, P < 0.01). LSM values increased gradually with an increased fibrosis stage. The areas under the ROC curves of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.837(95%CI: 0.729-0.914), 0.910(0.817-0.965), and 0.966(0.893-0.995), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.55, 10.50, and 14.45 k Pa, respectively. LSM was significantly superior to fibrosis-4, glutaglumyl-transferase/platelet ratio, and aspartate aminotransferase-to-platelet ratio index scores in detecting severe fibrosis(F ≥ 3)(0.910 vs 0.715, P < 0.01; 0.910 vs 0.649, P < 0.01; 0.910 vs 0.616, P < 0.01, respectively).CONCLUSION TE can accurately detect hepatic fibrosis as a noninvasive method in patients with AIH-PBC overlap syndrome.

Comparison of the liver stiffness measurement by transient elastography with the liver biopsy

AIM: To compare the liver stiffness (LS) measurement by transient elastography (TE) to the liver biopsy (LB)-considered the "gold standard" in the evaluation of patients with chronic hepatitis C. METHODS: During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus (HCV), in which LB and LS assessments (by means of TE) were performed during the same session. RESULTS: Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 ± 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with signifi cant fi brosis at biopsy (161 patients with F ≥ 2 according to Metavir) was 9.02 ± 5.15 kPa, significantly higher than in patients with no or mild fi brosis (30 patients with F < 2 Metavir): 5.39 ± 1.81 kPa (P < 0.0001). For a cut- off value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of signifi cant fi brosis (at least F2 Metavir), with a diagnostic performance of 77.3% (AUROC 0.773). Using this cut-off value, we reached the best discrimination between absence of fibrosis/ mild fibrosis (F < 2 Metavir) and the presence ofmoderate to severe fi brosis (F ≥ 2 Metavir). CONCLUSION: In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fi brosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.

Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography(Fibroscan~)

Unidimensional transient elastography(TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field.

Value of transient elastography for the prediction of variceal bleeding

AIM:To determine if liver stiffness(LS) measurements by means of transient elastography(TE) correlate with the presence of significant esophageal varices(EV) and if they can predict the occurrence of variceal bleeding.METHODS:We studied 1000 cases of liver cirrhosis divided into 2 groups:patients without EV or with grade 1 varices(647 cases) and patients with significant varices(grade 2 and 3 EV)(353 cases).We divided the group of 540 cases with EV into another 2 subgroups:without variceal hemorrhage(375 patients) and patients with a history of variceal bleeding(165 cases).We compared the LS values between the groups using the unpaired t-test and we established cut-off LS values for the presence of significant EV and for the risk of bleeding by using the ROC curve.RESULTS:The mean LS values in the 647 patients without or with grade 1 EV was statistically significantly lower than in the 353 patients with significant EV(26.29 ± 0.60 kPa vs 45.21 ± 1.07 kPa,P < 0.0001).Using the ROC curve we established a cut-off value of 31 kPa for the presence of EV,with 83% sensitivity(95%CI:79.73%-85.93%) and 62% specificity(95% CI:57.15%-66.81%),with 76.2% positive predictive value(PPV)(95% CI:72.72%-79.43%) and 71.3% negative predictive value(NPV)(95% CI:66.37%-76.05%)(AUROC 0.7807,P < 0.0001).The mean LS values in the group with a history of variceal bleeding(165 patients) was statistically significantly higher than in the group with no bleeding history(375 patients):51.92 ± 1.56 kPa vs 35.20 ± 0.91 kPa,P < 0.0001).For a cut-off value of 50.7 kPa,LS had 53.33% sensitivity(95% CI:45.42%-61.13%) and 82.67% specificity(95% CI:78.45%-86.36%),with 82.71% PPV(95% CI:78.5%-86.4%) and 53.66% NPV(95% CI:45.72%-61.47%)(AUROC 0.7300,P < 0.0001) for the prediction of esophageal bleeding.

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

Transient elastography is a recently developed non- invasive technique for the assessment of hepatic fi brosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratifi cation for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

Clinical applications, limitations and future role of transient elastography in the management of liver disease

Transient elastography(TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate noninvasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.

Ultrasound-based elastography for the diagnosis of portal hypertension in cirrhotics

Progressive fibrosis is encountered in almost all chronicliver diseases. Its clinical signs are diagnostic in advanced cirrhosis, but compensated liver cirrhosis is harder to diagnose. Liver biopsy is still considered the reference method for staging the severity of fibrosis, but due to its drawbacks(inter and intra-observer variability, sampling errors, unequal distribution of fibrosis in the liver, and risk of complications and even death), non-invasive methods were developed to assess fibrosis(serologic and elastographic). Elastographic methods can be ultrasound-based or magnetic resonance imaging-based. All ultrasoundbased elastographic methods are valuable for the early diagnosis of cirrhosis, especially transient elastography(TE) and acoustic radiation force impulse(ARFI) elastography, which have similar sensitivities and specificities, although ARFI has better feasibility. TE is a promising method for predicting portal hypertension in cirrhotic patients, but it cannot replace upper digestive endoscopy. The diagnostic accuracy of using ARFI in the liver to predict portal hypertension in cirrhotic patients is debatable, with controversial results in published studies. The accuracy of ARFI elastography may be significantly increased if spleen stiffness is assessed, either alone or in combination with liver stiffness and other parameters. Two-dimensional shearwave elastography, the Elast PQ technique and strain elastography all need to be evaluated as predictors of portal hypertension.

Transient elastography: A non-invasive tool for assessing liver fibrosis in HIV/HCV patients

AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviraltherapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (χ 2M H = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected pa-tients (χ 2 = 5, P < 0.03). Also APRI and the FIB-4 index showed more LF in co-infected than in HIV mono-infect-ed patients (P < 0.0001), but not in HCV mono-infected patients. In HIV?HCV co-infected patients, the extent of LS was significantly associated with alcohol intake (P < 0.04) and lower CD4+ cell count (P < 0.02). In HCV pa-tients, LS was correlated with alcohol intake (P < 0.001) and cholesterol levels (P < 0.03). Body mass index, dia-betes, HCV-and HIV-viremia were not significantly cor-related with LS. In addition, 20% of co-infected patients had virologically unsuccessful HAART; in 50% compliance was low, CD4+ levels were < 400 cells/mm 3 and LS was > 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.