Hepatic Fibrosis Stage Research Articles

Quantitative Imaging: Quantification of Liver Shape on CT Using the Statistical Shape Model to Evaluate Hepatic Fibrosis

To investigate the usefulness of the statistical shape model (SSM) for the quantification of liver shape to evaluate hepatic fibrosis. Ninety-one subjects (45 men and 46 women; age range, 20-75years) were included in this retrospective study: 54 potential liver donors and 37 patients with chronic liver disease. The subjects were classified histopathologically according to the fibrosis stage as follows: F0 (n=55); F1 (n = 6); F2 (3); F3 (n = 1); and F4 (n = 26). Each subject underwent contrast-enhanced computed tomography (CT) using a 64-channel scanner (0.625-mm slice thickness). An abdominal radiologist manually traced the liver boundaries on every CT section using an image workstation; the boundaries were used for subsequent analyses. An SSM was constructed by the principal component analysis of the subject data set, which defined a parametric model of the liver shapes. The shape parameters were calculated by fitting SSM to the segmented liver shape of each subject and were used for the training of a linear support vector regression (SVR), which classifies the liver fibrosis stage to maximize the area under the receiver operating characteristic curve (AUC). SSM/SVR models were constructed and were validated in a leave-one-out manner. The performance of our technique was compared to those of two previously reported types of caudate-right lobe ratios (C/RL-m and C/RL-r). In our SSM/SVR models, the AUC values for the classification of liver fibrosis were 0.96 (F0 vs. F1-4), 0.95 (F0-1 vs. F2-4), 0.96 (F0-2 vs. F3-4), and 0.95 (F0-3 vs. F4). These values were significantly superior to AUC values using the C/RL-m or C/RL-r ratios (P<.005). SSM was useful for estimating the stage of hepatic fibrosis by quantifying liver shape.

Dynamic changes of serum HBsAg levels at different grades of liver inflammation and stages of hepatic fibrosis in HBeAg-negative hepatitis B patients

To investigate the dynamic changes in serum levels of hepatitis B surface antigen (HBsAg) and their relation to hepatic parenchyma cell volume (hepatic cell quantity) at different grades of liver inflammation and stages of hepatic fibrosis in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Serum HBsAg levels were detected by electrochemilumineseence. Serum HBsAg levels were apportioned according to the hepatic parenchyma cell volume and compared among liver histological inflammation grade (1, 2, 3 and 4) and hepatic fibrosis stage ( I, II, III and IV), respectively. The levels of serum HBsAg among the four liver histological inflammation grades were:1:6,036.4+/-2,729.4 COI/ml; 2:6,704.6+/-2,457.5 COI/ml; 3:6,332.2+/-2,409.0 COI/ml; 4:6,226.2+/-2,716.0 COI/ml. There were no differences among the groups before apportion (Fbefore apportion=0.564, P=0.640).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume among liver histological inflammation grades were:1:9,174.8+/-4,142.0 COI/ml; 2:10,743.1+/-3,950.3 COI/ml; 3:11,078.0+/-4 230.0COI/ml; 4:11,540.5+/-5,058.8 COI/ml. There were significant differences among the groups after apportion (Fafter apportion =27.354, P<0.001). Serum HBsAg levels among hepatic fibrosis stages were: I: 6,222.1+/-2,665.4 COI/mL; II: 6,706.8+/-2,623.8 COI/ml; III:6 004.5+/-2,625.5 COI/ml; IV:6,455.6+/-2,344.4 COI/ml. There were no differences among groups before apportion (Fbefore apportion=0.768, P=0.513).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume (hepatic cell quantity) among hepatic fibrosis stages were: I :9 417.5+/-4,034.2 COI/ml; II :10,093.3+/-4,183.4 COI/ml; III:10,177.1+/-4,445.0 COI/ml; IV:12,166.6+/-4,418.5 COI/ml. There were significant differences among the groups after apportion (Fafter apportion=57.077, P<0.001). Serum HBsAg levels apportioned by the same hepatic parenchyma cell volume (hepatic cell quantity), rather than serum HBsAg levels, increased with hepatic pathological progress.

The association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C: an observational, multicenter study in Turkey.

To evaluate the association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C. A total of 104 chronic hepatitis C patients were included in this non-interventional, open-label, observational, multicenter, cross-sectional study conducted at 20 gastroenterology clinics in Turkey. The primary end point was the correlation between stage of hepatic fibrosis and insulin resistance evaluated via the homeostasis model of assessment-insulin resistance index. Confounders of hepatic fibrosis and insulin resistance were the secondary end points. The mean age of patients was 52.8 years; 65.4% were female. Type 2 diabetes was present in 6.8% and insulin resistance noted in 38.0% of patients. Further, 45.7% of the patients had mild (A0/A1) and the remaining had moderate/severe (A2/A3) hepatic necroinflammatory activity. Patient distribution according to Metavir fibrosis stage was as follows: F0/F1 (57.0%); F2 (6.5%); F3 (23.7%); and F4 (12.9%). A univariate analysis revealed significant positive correlations between Metavir fibrosis stage and insulin resistance (r=0.297; p=0.007). Logistic regression analysis showed that significant predictors of insulin resistance were high alanine transaminase levels (odds ratio, 0.97; 95% confidence interval, 0.944-0.997) and liver fibrosis stage (odds ratio, 0.114; 95% confidence interval, 0.021-0.607). Our findings revealed significant associations between insulin resistance and hepatic fibrosis.

New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment

New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment

Comparison of the diagnostic accuracies of magnetic resonance elastography and transient elastography for hepatic fibrosis

ObjectivesTo compare the diagnostic accuracies of magnetic resonance elastography (MRE) and transient elastography (TE) for hepatic fibrosis. Materials and MethodsThis retrospective study was approved by the institutional review board and included 113 patients (mean age, 63.1±12.2years; 84 men and 29 women) with chronic liver disease who underwent liver biopsy or resection, histopathologic assessment (METAVIR scoring system), and TE within 6months of MRE. Diagnostic accuracies of MRE and TE were compared using receiver operating characteristic curve analysis. Appropriate cutoff values of the two methods determined by maximum positive and minimum negative likelihood ratios were used to calculate the positive and negative predictive values for discriminating significant fibrosis (≥F2) from F0–F1 or cirrhosis (F4) from F0–F3. ResultsMean (95% confidence interval) area under the receiver operating characteristic curve values of MRE for cirrhosis (F4) (0.97 [0.93–0.99] vs. 0.93 [0.87–0.96]; P=0.0308), clinically significant fibrosis (≥F2) (0.98 [0.94–0.99] vs. 0.87 [0.79–0.92]; P=0.0003), and any fibrosis (≥F1) (0.97 [0.92–0.99] vs. 0.87 [0.76–0.93]; P=0.0126) were significantly higher than those of TE. By using the cutoff values derived from the maximum positive likelihood ratio, the positive and negative predictive values for≥F2 were 98.8% and 83.9%, respectively, by MRE and 98.2% and 44.8%, respectively, by TE; and for F4, 97.0% and 86.3%, respectively, by MRE and 95.8% and 77.5%, respectively, by TE. ConclusionMRE has better diagnostic accuracy than TE for staging hepatic fibrosis.

Nonalcoholic Fatty Liver Disease: Portal Hypertension Due to Outflow Block in Patients without Cirrhosis

To prospectively evaluate whether the characteristics of hepatic blood flow change during the early stages of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). All participants provided written informed consent, and the study protocols were approved by the institutional ethics committee. A total of 121 patients with NAFLD that was diagnosed at histologic examination were enrolled. Hepatic blood flow was measured by means of Doppler ultrasonography (US), and the ratio of arterial to portal blood flow (arterioportal ratio) was calculated. Elasticity of the spleen was measured by means of real-time tissue elastography. The elastic ratio was measured as the value in the small splenic vessel divided by the value of the splenic parenchyma. The arterioportal ratio and splenic elasticity were compared in patients with all stages of fibrosis (F0-F4) and with all levels of platelet counts. Correlations among the resistive index of the hepatic artery and that of the splenic artery, the fibrosis 4 index, hepatic elasticity, arterioportal ratio, splenic elasticity, and platelet counts were analyzed. Univariate and multivariate logistic regression analyses were performed. Correlations in patients with platelet counts greater than 200 000/μL also were analyzed. The mean ± standard deviation arterioportal ratio was significantly higher at fibrosis stage 2 (2.4 ± 0.6) than at fibrosis stage 0 (1.8 ± 0.4) in patients with NAFLD (P < .01). Increased splenic stiffness at earlier stages of fibrosis also was observed in patients with NAFLD (fibrosis stage 2, 4.4 ± 2.3; fibrosis stage 0, 3.2 ± 1.9; P < .05). In patients with NAFLD with platelet counts higher than 200 000/μL, pericellular fibrosis was the only significant predictor of hepatic hemodynamic change at multivariate analysis (odds ratio, 7.17; 95% confidence interval: 1.33, 57.13; P = .021). Change in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD because of outflow block in the sinusoidal area.

Diagnostic value of magnetic resonance elastography for detecting and staging of hepatic fibrosis: A meta-analysis

A meta-analysis was performed to evaluate the diagnostic value of magnetic resonance elastography (MRE) in detecting and staging hepatic fibrosis. A systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library Database up to October 2013 was undertaken to find studies on the evaluation of MRE in patients suspected of hepatic fibrosis. Data from the articles were analysed using Meta-disc 1.4 and Stata 12.0 software. The sensitivity, specificity, and area under the summary receiver operating characteristic (ROC) curve (AUROC) were pooled for all stages of hepatic fibrosis (F ≥ 1, F ≥ 2, F ≥ 3, and F = 4). Publication bias was assessed through the Deeks' funnel plot asymmetry tests. Thirteen studies comprising 989 patients met the inclusion criteria. The pooled sensitivity and specificity for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4 were 0.87 (95% CI = 0.84-0.89) and 0.92 (95% CI = 0.87-0.96), 0.87 (95% CI = 0.84-0.90) and 0.92 (95% CI = 0.89-0.95), 0.88 (95% CI = 0.85-0.91) and 0.91 (95% CI = 0.88-0.93), 0.91 (95% CI = 0.87-0.94) and 0.92 (95% CI = 0.89-0.94), respectively. The pooled AUROC for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4 were 0.9502, 0.9663, 0.9644, and 0.9768, respectively. The non-significant slope of Deeks' funnel plot asymmetry tests indicated that no significant bias was found. MRE has a high diagnostic accuracy for the quantitative detection and staging of hepatic fibrosis.

Accuracy of Real-Time Tissue Elastography for the Evaluation of Hepatic Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study

Background: The prognosis and management of hepatic fibrosis are closely related to the stage of the disease. The limitations of liver biopsy, which is the gold standard for treatment, include its invasiveness and sampling error. Ultrasound elasticity might be the most promising imaging technology for the noninvasive and accurate assessment of hepatic fibrosis. Real-time tissue elastography (RTE) measures the relative stiffness of the tissue in the region of interest caused by the heartbeat. Many studies have verified that RTE is useful for the diagnosis of hepatic fibrosis in patients with chronic hepatitis C (CHC). Purpose: To determine the formula of the liver fibrosis index for chronic hepatitis B (BLFI) and to validate the diagnostic accuracy of the BLFI for hepatic fibrosis compared with the liver fibrosis index (LFI). Materials and Methods: RTE was performed in 747 prospectively enrolled patients with chronic hepatitis B (CHB) or cirrhosis from 8 centers in China; 375 patients were analyzed as the training set, and 372 patients were evaluated as the validation set. The fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided liver biopsy. Nine image features were measured from strain images, and the new formula for the BLFI was obtained by combining the nine imaging features of the RTE images using multiple regression analysis of the training set. The BLFI and LFI were compared with the pathological fibrosis stage at diagnosis, and the diagnostic performances of the indexes were compared. Results: The Spearman correlation coefficient between the BLFI and hepatic fibrosis stages was significantly positive (r = 0.711, p < 0.001), and significant differences were present between all disease stages. The areas under the receiver-operating characteristic (AUROC) curves of the BLFI and LFI for predicting significant fibrosis (S0-S1 vs. S2-S4) were 0.858 and 0.858, respectively. For cirrhosis (S0-S3 vs. S4), the AUROC curves of the BLFI and LFI were 0.868 and 0.862, respectively. Conclusion: The results of this large, multicenter study confirmed that RTE is valuable for the diagnosis of hepatic fibrosis in patients with CHB. However, the diagnostic efficiencies of the new BLFI and the original LFI, which were based on CHC, for the assessment of CHB hepatic fibrosis were similar; thus, the LFI has the potential to be used to directly evaluate the extent of hepatic fibrosis in patients with CHB.

Factor VIII-Related Antigen Detects Phenotypic Change of Sinusoidal to Vascular Endothelium in Hepatic Fibrosis of Elderly Cadavers.

In advanced stages of hepatic fibrosis, the liver sinusoidal endothelium transforms to vascular endothelium with accompanying expression of factor VIII-related antigen (FVIIIRAg), a phenotypic marker of vascular endothelial cells. Liver fibrosis has been shown to be associated with aging and was found to be prevalent in elderly cadavers. Using immunohistochemistry, we studied FVIIIRAg expression in the livers of elderly cadavers with progressive stages of fibrosis. The vascular endothelium of portal tracts and central veins was stained for FVIIIRAg, providing an internal positive control. The incidence of FVIIIRAg expression was low in the sinusoids of livers that showed minimal fibrosis or perisinusoidal fibrosis but was increased in livers with advanced fibrosis (i.e., septa formation, bridging fibrosis, and cirrhosis). FVIIIRAg positive sinusoidal endothelial cells were distributed in loose aggregates in the periportal, periseptal, and midlobular parenchyma and were found less frequently in the centrilobular area. FVIIIRAg immune deposits appeared patchy and discontinuous along the sinusoidal lining, likely representing focalized transformation of sinusoidal to vascular endothelium. There was a discrete localization of FVIIIRAg immunoreactivity in the foci of severe parenchymal fibrosis. Conclusion. FVIIIRAg is a reliable marker for detecting the transformation of sinusoidal to vascular endothelium in advanced liver fibrosis in elderly cadavers.

MRI-based staging of hepatic fibrosis: Comparison of intravoxel incoherent motion diffusion-weighted imaging with magnetic resonance elastography

To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging.

Limited reliability of five non-invasive biomarkers in predicting hepatic fibrosis in chronic HCV mono-infected patients opposed to METAVIR scoring

BackgroundLiver biopsy is gold standard for fibrosis assessment in hepatitis C virus (HCV) infection but its limitations led to the identification of non-invasive biomarkers. This study assesses the reliability of five biomarkers in estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus METAVIR scoring. MethodsOne hundred HCV monoinfected patients who underwent liver biopsy and blood sampling were included. Liver fibrosis was staged (F0–4) and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl score were calculated and their receiver operating curves (ROCs), sensitivities, specificities, predictive values and accuracies were evaluated. ResultsThere were 27, 44, and 29 patients at F0–F1, F2–F3, and F4 groups. Significant statistical differences were found regarding AST, vireamia, platelet count, prothrombin time and all biomarkers. From ROCs only Pohl score predicted significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI showed moderate performance at low cut-offs, but had limited predictive values or accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic reliability of these biomarkers was limited to patients with suspected insignificant fibrosis. ConclusionsThis study verified the limited reliability for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic fibrosis in HCV infected patients opposed to METAVIR scoring.

Diagnostic accuracy of two-dimensional shear wave elastography for the non-invasive staging of hepatic fibrosis in chronic hepatitis B: a cohort study with internal validation.

To determine the accuracy of two-dimensional shear wave elastography (2D-SWE) for noninvasive staging of hepatic fibrosis in chronic hepatitis B (CHB). Patients with CHB infection who underwent liver biopsy were consecutively included. Receiver-operating characteristic (ROC) curves were constructed to assess the overall accuracy and identify optimal cutoff values. Three hundred three patients were analysed. The diagnostic performance characteristics were determined for the first 202 patients (the index cohort) and were validated on the next 101 patients (validation cohort). The areas under the ROC curves for significant fibrosis, severe fibrosis and cirrhosis were all greater than 0.90 and did not differ significantly between the index and validation cohorts. Using the cutoff values generated from the index cohort, the validation cohort 2D-SWE had negative predictive values of 82.6% (95% confidence interval [CI]: 68.4% - 92.3%) for significant fibrosis, 95.1% (95% CI: 86.3% - 99.0%) for severe fibrosis and 97.4% (95% CI: 90.8% - 99.7%) for cirrhosis. The positive predictive values were 83.6% (95% CI: 71.2% - 92.2%), 65.0% (95% CI: 48.1 - 79.5%) and 60.0% (95% CI: 38.7% - 78.9%), respectively. The 2D-SWE showed good diagnostic accuracy in staging liver fibrosis in patients with CHB infection and assisted in excluding liver fibrosis and cirrhosis. • Two-dimensional shear wave elastography showed good diagnostic accuracy in assessing liver fibrosis. • Diagnostic performance did not differ significantly between the index and validation cohorts. • Two-dimensional shear wave elastography assisted in excluding liver fibrosis and cirrhosis.

Hepatic Fibrosis: Prospective Comparison of MR Elastography and US Shear-Wave Elastography for Evaluation

To compare magnetic resonance (MR) elastography and ultrasonographic shear-wave elastography ( SWE shear-wave elastography ) for the staging of hepatic fibrosis ( HF hepatic fibrosis ) in the same individuals. This prospective study was approved by the institutional review board, and informed consent was obtained from all patients. The technical success of and reliable liver stiffness ( LS liver stiffness ) measurement rates at MR elastography and SWE shear-wave elastography were compared in 129 patients who underwent both examinations. For mutual validation, LS liver stiffness values measured at both examinations were correlated by using Pearson correlation. The diagnostic performance of the two techniques for the assessment of substantial HF hepatic fibrosis (stage ≥ F2) was compared by using nonparametric receiver operating characteristic analysis. The technical success rates of MR elastography and SWE shear-wave elastography were 95.35% (123 of 129) and 97.67% (126 of 129), respectively (P = .51). MR elastography provided significantly more reliable LS liver stiffness measurements than did SWE shear-wave elastography (95.35% [123 of 129] vs 75.2% [97 of 129], P < .001). The two examinations showed moderate correlation (r = 0.724). In patients with HF hepatic fibrosis stages of F3 or lower, the two examinations showed moderate-to-strong correlation (r = 0.683 in normal livers, 0.754 in livers with stage F0 or F1 HF hepatic fibrosis , and 0.90 in livers with stage F2 or F3 HF hepatic fibrosis ; P < .001); however, they did not show significant correlation for stage F4 HF hepatic fibrosis (r = 0.30, P = .31). MR elastography and SWE shear-wave elastography showed similar diagnostic capability in depicting HF hepatic fibrosis of stage F2 or greater (P = .98) when LS liver stiffness measurements were reliably performed. MR elastography and SWE shear-wave elastography showed moderate correlation and similar diagnostic performance in the diagnosis of HF hepatic fibrosis of stage F2 or greater; however, MR elastography yielded more reliable LS liver stiffness measurements than did SWE shear-wave elastography .

Renin-angiotensin system and fibrosis in non-alcoholic fatty liver disease.

Therapeutic options are limited for patients with non-alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation of necroinflammation and fibrosis by inhibition of the renin-angiotensin system (RAS). We explored whether the risk of fibrosis was associated with the use of commonly used medications in NAFLD patients with hypertension. Specifically, we sought to determine the association between RAS blocking agents and severity of hepatic fibrosis in NAFLD patients with hypertension. Cross-sectional study where clinical information including demographics, anthropometry, medical history, concomitant medication use, biochemical and histological features were ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients with and without RAS blocker use. Other risk factors for fibrosis were evaluated from the electronic medical records and patient follow-up. Baseline characteristics of hypertensive patients treated with and without RAS blockers were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01-1.06, P = 0.012) and presence of diabetes (OR: 2.55; 95%CI: 1.28-5.09, P = 0.008) had an independent positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21-0.65, P = 0.001) and statins (OR: 0.52; 95%CI: 0.29-0.93, P = 0.029) had a negative association with advanced fibrosis. Hypertensive patients with NAFLD on baseline RAS blockers had less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD.

MR elastography for the assessment of hepatic fibrosis in patients with chronic hepatitis B infection: does histologic necroinflammation influence the measurement of hepatic stiffness?

To determine the diagnostic performance of magnetic resonance (MR) elastography for the staging of hepatic fibrosis and to evaluate the influence of necroinflammation on hepatic stiffness in patients with chronic hepatitis B virus (HBV) infection by using histopathologic findings as the reference standard. One hundred thirteen consecutive patients with chronic HBV infection were recruited prospectively in this institutional review board-approved study after providing written informed consent between March 2012 and October 2013. The stiffness measurements were obtained by using two-dimensional gradient-echo MR elastography with a 3.0-T MR system. The METAVIR scoring system was used for the assessment of fibrosis ("F" stage) and necroinflammation ("A" grade). The predictive ability of MR elastography was evaluated by using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). Multiple linear regression analyses were conducted to determine the relationship between hepatic stiffness and the variables that showed a significant association in the univariate analysis or those that were of interest for comparison with earlier work (histologic scores, sex, age, aspartate aminotransferase level, and aspartate aminotransferase/alanine aminotransferase ratio). MR elastography showed excellent performance for characterization of ≥ F1, ≥ F2, ≥ F3, and F4 findings, with AUC values of 0.961, 0.986, 1.000, and 0.998, respectively. It showed a moderate capability for evaluation of necroinflammatory activity of ≥ A1, ≥ A2, and A3 (AUC = 0.806, 0.834, and 0.906, respectively). Multiple linear regression analysis showed that fibrosis, necroinflammation, and sex were independently associated with hepatic stiffness (β = 0.799, 0.277, and 0.070, respectively; P < .05). For pairwise comparisons, log-transformed hepatic stiffness showed no difference between (a) groups F0/A2-3 and F1/A0-1 and (b) groups F1/A2-3 and F2/A0-1 (P > .99 and P = .486, respectively). MR elastography demonstrated excellent performance for distinguishing the stages of hepatic fibrosis in patients with chronic HBV infection. For hepatic tissue with ≤ F2 fibrosis, necroinflammation can account for a substantial fraction of the increase in hepatic stiffness.

Apparent diffusion coefficient value of hepatic fibrosis and inflammation in children with chronic hepatitis.

This study was done to prospectively evaluate the usefulness of apparent diffusion coefficient (ADC) in the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis. Institutional Review Board approval was obtained. This prospective study was carried out on 50 children with chronic hepatitis (mean age 8.3±3.2years; 33 boys and 17 girls) and 20 age- and sex-matched healthy control children. The children underwent diffusion-weighted magnetic resonance imaging of the liver. The ADC value of the liver was calculated. The hepatic fibrosis stages (F1-F6) and necroinflammatory activity grades (A1-A4) were calculated. The ADC values of different stages of hepatic fibrosis and grades of necroinflammatory activity were calculated. The mean ADC value of the liver parenchyma was 1.53±0.17×10(-3)mm(2)/s in children with chronic hepatitis and 1.74±0.16×10(-3)mm(2)/s in controls. The ADC value was significantly lower in children with hepatic fibrosis compared to controls (p=0.001). There was a significant difference (p=0.001) in ADC between mild (F1-F3) and advanced (F4-F6) stages of fibrosis. There was a significant difference (p=0.004) in ADC between mild (A1-A2) and advanced (A3-A4) grades of necroinflammation. The cut-off ADC values used to differentiate mild from advanced fibrosis and necroinflammation were 1.62 and 1.64mm(2)/s with an area under the curve of 0.898 and 0.807, respectively. The ADC value negatively correlated with stages of hepatic fibrosis (r=-0.799, p=0.001) and necroinflammatory activity grade (r=-0.468, p=0.001). We conclude that ADC value is an effective noninvasive parameter for the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis.

Noninvasive Biomarkers of Liver Fibrosis: An Overview

Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis.

Magnetic resonance elastography and acoustic radiation force impulse for staging hepatic fibrosis: a meta-analysis

Elastography is a non-invasive method to quantify fibrosis based on tissue mechanical properties. We performed a meta-analysis to assess the diagnostic accuracy of two such techniques: Acoustic Radiation Force Impulse Imaging (ARFI) or Magnetic Resonance Elastography (MRE) for staging hepatic fibrosis. Literature databases were searched until June 2013. Inclusion criteria were evaluation of MRE or ARFI, liver biopsy, and reported sensitivity and specificity. A random effects model was used to combine sensitivity and specificity, from which positive (LR+) and negative (LR-) likelihood ratios, diagnostic odds ratios, and area under receiver operating characteristics curve (AUROC) were derived. Differences between MRE and ARFI were compared with t tests (P < 0.05 considered significant). Eleven MRE studies including 982 patients and fifteen ARFI studies including 2,128 patients were selected. AUROC for MRE staging fibrosis were 0.94, 0.97, 0.96, and 0.97 for F1-F4, respectively, whereas AUROC for ARFI staging were 0.82, 0.85, 0.94, and 0.94 for F1-F4, respectively. Significance was found in AUROC between MRE and ARFI for the diagnosis of stage 1 and 2 fibrosis. MRE is more accurate than ARFI with a higher combination of sensitivity, specificity, LR, and AUROC particularly in diagnosing early stages of hepatic fibrosis.

Maximum likelihood estimation of shear wave speed in transient elastography.

Ultrasonic transient elastography (TE), enables to assess, under active mechanical constraints, the elasticity of the liver, which correlates with hepatic fibrosis stages. This technique is routinely used in clinical practice to assess noninvasively liver stiffness. The Fibroscan system used in this work generates a shear wave via an impulse stress applied on the surface of the skin and records a temporal series of radio-frequency (RF) lines using a single-element ultrasound probe. A shear wave propagation map (SWPM) is generated as a 2-D map of the displacements along depth and time, derived from the correlations of the sequential 1-D RF lines, assuming that the direction of propagation (DOP) of the shear wave coincides with the ultrasound beam axis (UBA). Under the assumption of pure elastic tissue, elasticity is proportional to the shear wave speed. This paper introduces a novel approach to the processing of the SWPM, deriving the maximum likelihood estimate of the shear wave speed when comparing the observed displacements and the estimates provided by the Green's functions. A simple parametric model is used to interface Green's theoretical values of noisy measures provided by the SWPM, taking into account depth-varying attenuation and time-delay. The proposed method was evaluated on numerical simulations using a finite element method simulator and on physical phantoms. Evaluation on this test database reported very high agreements of shear wave speed measures when DOP and UBA coincide.

NONINVASIVE ASSESSMENT OF HEPATIC FIBROSIS

Staging of hepatic fibrosis is crucial for prognosis, surveillance and treatment decision in patients with chronic liver diseases in clinical practice. Liver biopsy has still the gold standard for assessment of hepatic fibrosis, but it has some limitations. To overcome this, non-invasive methods were developed. The methods of noninvasive assessment of liver fibrosis were divided into two main groups: serum biomarkers and techniques measuring liver stiffness. Each method has its own advantages and limits. Some studies suggest that the effectiveness of noninvasive methods for assessing liver fibrosis may increase when they are combined. The aim of this article is to review and update the different non invasive methods for assessment of hepatic fibrosis, their advantages, disadvantages, diagnostic accuracy and their applications in clinical practice. Key words: hepatic fibrosis, liver stiffness, chronic liver disease