Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.

Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl_4-induced liver fibrosis

AIM To investigate the diagnostic performance of liver stiffness measurement(LSM) by elastography point quantification(Elast PQ) in animal models and determine the longitudinal changes in liver stiffness by Elast PQ after splenectomy at different stages of fibrosis.METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by Elast PQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by Elast PQ and liver function according to blood tests.RESULTS LSM by Elast PQ was significantly correlated with histologic fibrosis stage(r = 0.85, P < 0.001). The optimal cutoff values by Elast PQ were 11.27, 14.89, and 18.21 k Pa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinalmonitoring of the changes in liver stiffness by Elast PQ showed that early splenectomy(especially F1) may delay liver fibrosis progression.CONCLUSION Elast PQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using Elast PQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry

AIM To evaluate the diagnostic performance of computed tomography(CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease(NAFLD).METHODS A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment(LLS), left medial segment, caudate lobe, and right lobe(RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic(ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage.RESULTS The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage(r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage(r =-0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis(F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity.CONCLUSION The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients.

Diagnostic value of two dimensional shear wave elastography combined with texture analysis in early liver fibrosis

BACKGROUND Staging diagnosis of liver fibrosis is a prerequisite for timely diagnosis and therapy in patients with chronic hepatitis B.In recent years,ultrasound elastography has become an important method for clinical noninvasive assessment of liver fibrosis stage,but its diagnostic value for early liver fibrosis still needs to be further improved.In this study,the texture analysis was carried out on the basis of two dimensional shear wave elastography(2D-SWE),and the feasibility of 2D-SWE plus texture analysis in the diagnosis of early liver fibrosis was discussed.AIM To assess the diagnostic value of 2D-SWE combined with textural analysis in liver fibrosis staging.METHODS This study recruited 46 patients with chronic hepatitis B.Patients underwent 2DSWE and texture analysis;Young's modulus values and textural patterns were obtained,respectively.Textural pattern was analyzed with regard to contrast,correlation,angular second moment(ASM),and homogeneity.Pathological results of biopsy specimens were the gold standard;comparison and assessment of the diagnosis efficiency were conducted for 2D-SWE,texture analysis and their combination.RESULTS 2D-SWE displayed diagnosis efficiency in early fibrosis,significant fibrosis,severe fibrosis,and early cirrhosis(AUC>0.7,P<0.05)with respective AUC values of 0.823(0.678-0.921),0.808(0.662-0.911),0.920(0.798-0.980),and 0.855(0.716-0.943).Contrast and homogeneity displayed independent diagnosis efficiency in liver fibrosis stage(AUC>0.7,P<0.05),whereas correlation and ASM showed limited values.AUC of contrast and homogeneity were respectively 0.906(0.779-0.973),0.835(0.693-0.930),0.807(0.660-0.910)and 0.925(0.805-0.983),0.789(0.639-0.897),0.736(0.582-0.858),0.705(0.549-0.883)and 0.798(0.650-0.904)in four liver fibrosis stages,which exhibited equivalence to 2D-SWE in diagnostic efficiency(P>0.05).Combined diagnosis(PRE)displayed diagnostic efficiency(AUC>0.7,P<0.01)for all fibrosis stages with respective AUC of 0.952(0.841-0.994),0.896(0.766-0.967),0.978(0.881-0.999),0.947(0.835-0.992).The combined diagnosis showed higher diagnosis efficiency over 2D-SWE in early liver fibrosis(P<0.05),whereas no significant differences were observed in other comparisons(P>0.05).CONCLUSION Texture analysis was capable of diagnosing liver fibrosis stage,combined diagnosis had obvious advantages in early liver fibrosis,liver fibrosis stage might be related to the hepatic tissue hardness distribution.

Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characterization,and hepatic fibrosis staging are highly relevant for controlling transmission,treating infected patients and,consequently,avoiding end-stage liver disease.Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays.Additionally,the use of point-of-care tests can increase HCV screening opportunities.However,active HCV infection must be confirmed by direct diagnosis methods.Additionally,HCV genotyping is required prior to starting any treatment.Increasingly,high-volume clinical laboratories use different types of automated platforms,which have simplified sample processing,reduced hands-on-time,minimized contamination risks and human error and ensured full traceability of results.Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods,such as imaging techniques and serum-based tests.However,no single test is currently available that is able to completely replace liver biopsy.This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests.

Magnetic resonance-based total liver volume and magnetic resonance-diffusion weighted imaging for staging liver fibrosis in mini-pigs

AIM:To determine whether and how magnetic resonance imaging(MRI)-based total liver volume(TLV) and diffusion weighted imaging(DWI) could predict liver fibrosis.METHODS:Sixteen experimental mature mini-pigs(6 males,10 females),weighing between 20.0 and 24.0 kg were prospectively used to model liver fibrosis induced by intraperitoneal injection of 40% CCl4 dissolved in fat emulsion twice a week for 16 wk,and by feeding 40% CCl4 mixed with maize flour twice daily for the subsequent 5 wk.All the survival animals underwent percutaneous liver biopsy and DWI using b = 300,500 and 800 s/mm2 followed by abdominal gadolinium-enhanced MRI at the 0,5th,9th,16th and 21st weekend after beginning of the modeling.TLV was obtained on enhanced MRI,and apparent diffusion coefficient(ADC) was obtained on DWI.Hepatic tissue specimens were stained with hematoxylin and Masson' s trichrome staining for staging liver fibrosis.Pathological specimens were scored using the human METAVIR classification system.Statistical analyses were performed to determine whether and how the TLV and ADC could be used to predict the stage of liver fibrosis.RESULTS:TLV increased from stage 0 to 2 and decreased from stage 3(r = 0.211;P < 0.001).There was a difference in TLV between stage 0-1 and 2-4(P = 0.03) whereas no difference between stage 0-2 and 3-4(P = 0.71).TLV could predict stage ≥ 2 [area under receiver operating characteristic curve(AUC) = 0.682].There was a decrease in ADC values with increasing stage of fibrosis for b = 300,500 and 800 s/mm2(r =-0.418,-0.535 and-0.622,respectively;all P < 0.001).Differences were found between stage 0-1 and 2-4 in ADC values for b = 300,500 and 800 s/mm2,and between stage 0-2 and 3-4 for b = 500 or 800 s/mm2(all P < 0.05).For predicting stage ≥ 2 and ≥ 3,AUC was 0.803 and 0.847 for b = 500 s/mm2,and 0.848 and 0.887 for b = 800 s/mm2,respectively.CONCLUSION:ADC for b = 500 or 800 s/mm2 could be better than TLV and ADC for b = 300 s/mm2 to pre-dict fibrosis stage ≥ 2 or ≥ 3.

Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis C

AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse (ARFI) elastograpy in chronic hepatitis C.

Histological outcome of chronic hepatitis B in children treated with interferon alpha

AIM： To evaluate the effect of interferon alpha （IFN-α） treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients. METHODS： Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig, Ishak et al., and IETAVIR （only fibrosis stage） before and 12 mo after IFN-α treatment termination in 93 children aged 2-16 years with chronic hepatitis B. RESULTS： None of the three numerical scoring systems for liver fibrosis showed statistically significant differences in liver fibrosis, while evolution of inflammatory activity revealed statistically significant improvement in the whole group of children with chronic hepatitis B treated with IFN-α and in responders. Significantly positive correlations were found between fibrosis stage and inflammation grade in the respective scoring systems. CONCLUSION： Treatment with IFN-α did not improve histological fibrosis but decreased inflammatory activity in children with chronic hepatitis B. The three semiquantitative scoring systems seem to be comparable in the estimation of the inflammation grade and fibrosis stage in this group of children.

CCL2-2518 A/G and CCR2 190 A/G do not influence the outcome of hepatitis C virus infection in the Spanish population

AIM： To assess whether CCL2 or interactions between this chemokine and its receptor （CCR2） are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy. METHODS： Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 （/7 = 202） or F3-F4 （/7 = 82） and according to their response to anti-Hepatitis C virus （HCV） therapy as sustained response （SR, n = 201） or non-sustained response （NSR, n = 98）. Genotyping of the -2518 （A/G） CCL2 was performed using PCR-RFLP, genotyping of the 190 （A/G） CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 （G/A） CCR2 using Taqman probes. RESULTS： Univariate analyses identified 4 parameters （infection duration time, viral genotype, gender and AST levels） that tended to influence fibrosis and 7 parameters （CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels） that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment. CONCLUSION： Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.