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.

Point shear wave elastography method for assessing liver stiffness

AIM:To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness.METHODS:This was a single-center,cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy(LB)(Group 1)and healthy volunteers(Group 2)were studied.In each subject 10 consecutive point shear-wave elastography(PSWE)measurements were performed using the iU22 ultrasound system(Philips Medical Systems,Bothell,WA,United States).Patients in Group 1 underwent PSWE,transient elastography(TE)using FibroScan(Echosens,Paris,France)and ultrasound-assisted LB.For the assessment of PSWE reproducibility two expert raters(rater 1 and rater 2)independently performed the examinations.The performance of PSWE was compared to that of TE using LB as a reference standard.Fibrosis was staged according to the METAVIR scoring system.Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve(AUC)for F≥2,F≥3and F=4.The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin’s concordance correlation coefficient.RESULTS:To assess the performance of PSWE,134consecutive patients in Group 1 were studied.The median values of PSWE and TE(in kilopascals)were 4.7(IQR=3.8-5.4)and 5.5(IQR=4.7-6.5),respectively,in patients at the F0-F1 stage and 3.5(IQR=3.2-4.0)and 4.4(IQR=3.5-4.9),respectively,in the healthy volunteers in Group 2(P<10-5).In the univariate analysis,the PSWE and TE values showed a high correlation with the fibrosis stage;low correlations with the degree of necroinflammation,aspartate aminotransferase and gamma-glutamyl transferase(GGT);and a moderate negative correlation with the platelet count.A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables.The following AUC values were found:0.80(0.71-0.87)for PSWE and 0.82(0.73-0.89)for TE(P=0.42);0.88(0.80-0.94)for PSWE and 0.95(0.88-0.98)for TE(P=0.06);and 0.95(0.89-0.99)for PSWE and 0.92(0.85-0.97)for TE(P=0.30)for F≥2,F≥3 and F=4,respectively.To assess PSWE reproducibility,116 subjects were studied,including 47consecutive patients scheduled for LB(Group 1)and 69 consecutive healthy volunteers(Group 2).The intraobserver agreement ranged from 0.83(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 1 and from 0.84(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 2.The interobserver agreement yielded values from0.83(95%CI:0.78-0.88)to 0.93(95%CI:0.91-0.95).CONCLUSION:PSWE is a reproducible method for assessing liver stiffness,and it compares with TE.Compared with patients with nonsignificant fibrosis,healthy volunteers showed significantly lower values.

Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis

AIM:To assess the performance of controlled attenuation parameter(CAP)in patients with chronic viral hepatitis.METHODS:CAP is a new technique that measures the attenuation in the liver of an ultrasound beam,which is directly related to lipid accumulation.Consecutive patients undergoing liver biopsy for chronic viral hepatitis were studied using the M probe of FibroScan device(Echosens,Paris,France).The device estimates liver st-eatosis in decibel per meter(dB/m).An expert operator performed all measurements.Steatosis was graded according to Kleiner’s classification.Pearson or Spearman rank coefficient was used to test correlation between two study variables.Linear regression was used for multivariate model to assess the association between CAP and other variables.Receiver operating characteristic curve analysis was performed to calculate area under the curve(AUROC)for S0 vs S1-S3 and S0-S1 vs S2-S3.RESULTS:115 subjects(85 males and 30 females)were prospectively studied.The mean values of CAP were 227.1±43.1 for S0;254.6±38.9 for S1;297.8±49.4 dB/m for S2-S3.In univariate analysis CAP showed a significant correlation with age,body mass index(BMI),degree of steatosis,and cholesterol.Multivariate regression analysis confirmed the correlation with the degree of steatosis[coefficient,1.2(0.60-1.83);P<10-5]and BMI[coefficient,4.1(0.5-7.8);P=0.03]but not with all other variables.Optimal cutoff values for S≥1 and S≥2 were 219 dB/m[AUROC,0.76(0.67-0.84);sensitivity,91.1%(78.8-97.5);specificity,51.6%(38.7-64.2);positive predictive value,56.9%(44.7-68.6);negative predictive value,89.2%(74.3-97.0);positive likelihood ratio,1.88(1.4-2.5);negative likelihood ratio,0.17(0.07-0.5)]and 296 dB/m[AUROC,0.82(0.74-0.89);sensitivity,60.0%(32.3-83.7);specificity,91.5%(83.9-96.3);positive predictive value,52.9%(27.8-77.0);negative predictive value,93.5%(86.3-97.6);positive likelihood ratio,7.05(3.2-15.4);negative likelihood ratio,0.44(0.2-0.8)],respectively.CONCLUSION:Controlled attenuation parameter could be a useful tool in the clinical management of patients with chronic viral hepatitis for detecting liver steatosis.

Carrier frequency of HLA-DQB1*02 allele in patients affected with celiac disease:A systematic review assessing the potential rationale of a targeted allelic genotyping as a first-line screening

BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.