Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Gd-EOB-DTPA-enhanced MRI-a noninvasive and short-term assessment method for liver necroinflammation after direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C.

PURPOSE: To assess liver necroinflammation in HCV patients undergone antiviral therapy by Gd-EOB-DTPA-enhanced MRI with histopathologic analyses as reference. METHODS: HCV patients were enrolled in this prospective study before antiviral treatment between 09-2016 and 07-2017. Unenhanced MR, Gd-EOB-DTPA-enhanced MR, and liver biopsy were performed before and 24 weeks after treatment of daclatasvir with asunaprevir (DAA). DWI was obtained using a breath-hold single-shot echo planar spin-echo sequence. Twenty minutes after administration of Gd-EOB-DTPA, the relative enhancement (RE) and the contrast enhancement index (CEI) were recorded. Liver necroinflammatory activity grades (G0-18) were categorized on the Ishak Scoring systems. CEI, RE, and DWI of baseline and 24 weeks after treatment were compared by paired t test. Relationship between MR parameters and histologic scores was evaluated by Pearson's correlation. Receiver operating characteristic analysis evaluated the measurements' diagnostic performance. MRI variability between two readers was assessed using the intraclass correlation coefficient.Results RESULTS: A decrease of liver necroinflammatory activity grade (p < 0.0001) was detected in final cohort (n = 21; mean age 44 years; 23 to 67 years; 11 F, 10 M). Statistical results of 42 person-times in 21 patients at baseline and follow-up showed CEI and ADC were significantly different (p = 0.006 and 0.036) across histologic grades of liver necroinflammation. Significant increase of CEI, RE, and ADC (p = 0.0004, 0.0032, 0.0110) 24 weeks after DAA treatment was seen. Additionally, CEI was correlated to necroinflammatory grade (r = - 0.596, p = 0.006). AUROC for CEI, ADC, and CEI combined with ADC to differentiate patients with none and mild (G0-6) from patients with moderate and severe necroinflammation (G7-18) was 0.834 (95% CI 0.712-0.956, 0.724(95% CI 0.565-0.884) and 0.837(95% CI 0.717-0.956). CONCLUSION: Gd-EOB-DTPA-enhanced MRI by CEI could be used as a noninvasive imaging biomarker to distinguish grades of necroinflammatory activity in patients with HCV after DAAs therapy at early stage and CEI combined with ADC could get a better diagnostic accuracy.

Comparative study between two 2D-Shear Waves Elastography techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.

AIMS: We aimed to compare the diagnostic performance of two 2D-Shear Wave Elastography (2D-SWE) techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection using Transient Elas-tography (TE) as reference. MATERIAL AND METHODS: We enrolled 208 consecutive patients with chronic HCV infection, in which liver stiffness (LS) was evaluated in the same session using two 2D-SWE techniques: 2D-SWE.GE and 2D-SWE.SSI using TE as the method of reference. LS measurements were considered failures when no value was obtained after 10 attempts. RESULTS: Valid LSMs were obtained in 95.6% (199/208) of cases by 2D-SWE.GE, 92.7% (193/208) of cases by 2D-SWE.SSI, and in 94.7% (197/208) of cases by TE (p>0.05). The mean LS values by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI: 10.3±3.8 kPa vs. 15±10.4 kPa (p<0.0001). 2D-SWE.GE LSMs correlated better with TE than 2D-SWE.SSI (r=0.75, p<0.0001 vs. r=0.57, p<0.0001, z test p=0.0012). Linear regression analysis showed a moderate correlation between LSMs obtained by 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R2=0.4, P<0.0001). Pairwise comparison of receiver operating characteristics curves (ROC) found no significant differences between 2D-SWE.GE and 2D-SWE.SSI in identifying F≥2 fibrosis (0.97 vs. 0.96, P = 0.5650), F≥3 (0.97 vs. 0.95, P = 0.2935), or F=4 (0.97 vs. 0.96, p = 0.6914). CONCLUSIONS: Both 2D-SWE techniques had good feasibility for the noninvasive assessment of liver fibrosis. LS values obtained by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI. No significant differences were found between both methods in staging liver fibrosis in patients with chronic HCV.

Comparative Study Between the Diagnostic Performance of Point and 2-D Shear-Wave Elastography for the Non-invasive Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C Using Transient Elastography as Reference.

The study compared the diagnostic performance of two shear-wave elastography techniques, elastography point quantification (ElastPQ) and 2-D shear-wave elastography by General Electric (2-D-SWE.GE), for the non-invasive assessment of liver fibrosis in a cohort of patients with chronic hepatitis C virus (HCV) infection, using transient elastography (TE) as the reference method. There was no significant difference between the feasibility rates of TE, ElastPQ and 2-D-SWE.GE (p = 0.507). A good correlation was found between the liver stiffness (LS) values obtained using the two elastographic methods (r = 0.78). The mean LS values obtained using the ElastPQ technique were significantly higher than those obtained using 2-D-SWE.GE (12.1 ± 7.3 kPa vs. 10.4 ± 4.0 kPa, p < 0.0001). Pairwise comparisons of receiver operator characteristics curves between 2-D-SWE.GE and ElastPQ have shown that there are no significant differences in their performance for staging F ≥ 2 fibrosis (p = 0.89), F ≥ 3 fibrosis (p = 0.76) and F = 4 fibrosis (p = 0.86) in patients with chronic HCV infection.

Noninvasive liver fibrosis assessment in chronic viral hepatitis C: agreement among 1D transient elastography, 2D shear wave elastography, and magnetic resonance elastography.

PURPOSE: To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. METHODS: Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis. RESULTS: Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance. CONCLUSIONS: MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B or C by Contrast-Enhanced Magnetic Resonance Imaging.

Background and Aim. To develop a noninvasive magnetic resonance imaging (MRI) method for evaluation of liver fibrosis. We evaluate the utility of hepatocyte-phase Gadoxetate disodium-enhanced magnetic resonance (MR) imaging in staging hepatic fibrosis and compare it with histological analysis as the reference standard (liver biopsy). Methods. Prospective cohort of 78 patients, who received Gadoxetate disodium dynamic contrast-enhanced MRI (DCE-MRI), were divided into three groups. The first group (n=19) was a control group of healthy individuals without liver injury and remaining 59 subjects were chronic hepatitis B and C patients who underwent liver biopsy. These patients were divided into the mild fibrosis F1-F2 (n=32) and advanced fibrosis F3-F4 (n=27) groups. Patients were examined by generated DCE-MRI in 20th minute. Variables such as liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR were evaluated and these results were consequently compared between the three groups. Results. Gd-EOB-DTPA contrast-enhanced dynamic liver MRI examination (DCE-MRI) can in the 20th minute differentiate mild stage of liver fibrosis (F1-F2) from severe stage of liver fibrosis (F3-F4) on the basis of liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR. Diagnostic MRI criteria were created and named MRI Triple test. This test correctly identified 96% of patients with F3-F4 fibrosis and 91% of patients with the F1-F2 fibrosis in the liver biopsy. This test correctly identified 42,1% of patients in the control group (presumed F0 fibrosis without liver disease). Spearman's rank correlation coefficient (r = 0,86, P < .001) confirmed high agreement of biopsy and MR Triple test. MR Triple test's sensitivity was 96.30% (95%CI 81.03% to 99.91%), specificity 90.62% (95%CI 74.98% to 98.02%), positive predictive value 89.66% (95%CI 74.64% to 96.23%), and negative predictive value 96.67% (95%CI 80.86% to 99.50%) for discrimination between F3-4 and F1-2 fibrosis on liver biopsy. Conclusions. Gd-EOB-DTPA contrast-enhanced MRI liver examination in 20th minute is able to reliably differentiate mild stage of liver fibrosis (F1-F2) from severe stage fibrosis (F3-F4) on the basis of Triple test (liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR).

Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis.

BACKGROUND: This study investigated the relationship between liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis. We used an acoustic radiation force impulse (ARFI) technique to measure stiffness, and a radio frequency (RF) vascular quantitative ultrasound technique to measure changes in common carotid artery elasticity and vascular function. METHODS: Two-hundred seventeen patients with chronic viral hepatitis caused by either hepatitis B virus (HBV) or hepatitis C virus (HCV) were enrolled. We divided the patients into two groups, one comprising 147 patients with chronic hepatitis B (CHB) (98 men and 49 women, average age 46.5 ± 12.2 years) and another comprising 70 patients with chronic hepatitis C (CHC) (47 men and 23 women, average age 47.6 ± 12.1 years). Additionally, 64 healthy age- and sex-matched participants (43 men and 21 women, average age 47.8 ± 5.1 years) were selected as the control group. The ARFI technique was used to measure liver stiffness and the RF ultrasound technique was used to measure carotid artery elasticity parameters including intima-media thickness (IMT), pulse wave velocity (PWV), arterial wall dilation coefficient (DC), compliance coefficient (CC), sclerosis indices α and ß, and augmentation index (Aix). Clinical indicators, liver stiffness, and carotid artery elasticity parameters were observed and compared between the different age groups to investigate the correlation between carotid artery elasticity parameters and liver stiffness. RESULTS: The ARFI values for the CHB and CHC groups were significantly higher than those for the control group (1.84 ± 0.52 vs. 1.04 ± 0.11 m/s; 1.86 ± 0.37 vs. 1.04 ± 0.11 m/s, respectively; P < 0.001). When compared to the control group, both CHB and CHC groups showed an IMT of the same order, but had significantly higher elasticity parameters, such as α and ß, as well as lower DC and CC values (P < 0.001). The PWV of the CHC group was significantly higher than that of the control group (7.98 ± 1.42 vs. 6.09 ± 0.90 m/s, P < 0.001). In the CHB group, all parameters including ARFI, IMT, PWV, DC, CC, α and ß, were significantly different between the two age groups (P < 0.05). Within the CHC group, all parameters including IMT, PWV, DC, α and ß, were significantly different between the two age groups (P < 0.05), except for ARFI, wherein the difference was not statistically significant. The correlation analysis and stepwise multiple linear regression analysis indicated that for patients with CHB, age was an independent predictor of common carotid artery IMT (R2 = 0.468, F = 54.635, and P < 0.001). For patients with CHC, age and blood sugar were independent predictors of common carotid artery IMT (R2 = 0.465, F = 29.118, and P < 0.001). CONCLUSION: Although based on ARFI and RF ultrasound, the carotid artery IMT in patients with CHB and CHC was not significantly higher than that in the control group, their functional elasticity parameters had already changed. This finding serves as a useful reference for the clinical diagnosis of vascular diseases in patients with viral hepatitis. TRIAL REGISTRATION: ClinicalTrials: ChiCTR1800015859 25/04/2018.

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging.

AIM: To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B/C (CHB/C). METHODS: We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions (HeF) and relaxation time reduction rate (RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between HeF and RE. RESULTS: A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23 (31.5%); F1, n = 19 (26.0%); F2, n = 13 (17.8%); F3, n = 6 (8.2%), and F4, n = 12 (16.4%). HeF by EOB enhancement imaging was significantly correlated with fibrosis stage (r = -0.808, P < 0.05). AUC values for diagnosis of any (≥ F1), significant (≥ F2) or advanced (≥ F3) fibrosis, and cirrhosis (F4) using HeF were 0.837 (0.733-0.913), 0.890 (0.795-0.951), 0.957 (0.881-0.990), and 0.957 (0.882-0.991), respectively. HeF measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of HeF is a superior noninvasive liver fibrosis staging method. CONCLUSION: A T1 mapping-based HeF method is an efficient diagnostic tool for the staging of liver fibrosis.

Effect of Hepatic Inflammation in Chronic Hepatitis C Infection on Fibrosis Assessment by Arrival Time Parametric Imaging.

Arrival time parametric imaging (At-PI) in contrast-enhanced ultrasonography is useful for assessing liver fibrosis in chronic hepatitis C (CHC) infection. The study aimed to elucidate the effect of hepatic inflammation on At-PI efficiency. Subjects were 159 CHC patients who underwent contrast-enhanced ultrasonography immediately before liver biopsy. Ultrasound contrast agent was injected, and contrast dynamics of the S5 to S6 region of the liver and right kidney were recorded for 40 seconds. The At-PI of liver parenchyma blood flow was generated using saved video clips. Hepatic blood flow during the first 5 seconds after starting contrast injection was displayed in red and that after another 5 seconds was displayed in yellow. The ratio of red (ROR) in At-PI images of the entire liver was measured with ImageJ. Ratio of red values of livers with different activity grades (0-3) were compared for each fibrosis (F) stage as determined by biopsy. Correlations of ROR with alanine aminotransferase (ALT) levels were analyzed using a linear regression line from the distribution map. Comparison of ROR for different activity grades in each F stage revealed no significant differences. Correlation coefficient R (P value) for ALT and ROR was R = -0.0094 (P = 0.43) at F0 to F1, R = -0.186 (P = 0.21) at F2, R = -0.233 (P = 0.27) at F3, and R = 0.041 (P = 0.89) at F4, with no significant correlation between ALT and ROR in any F stage. Hepatic inflammation in CHC infection does not affect At-PI diagnostic accuracy.

Elastogram quality assessment score in vibration-controlled transient elastography: Diagnostic performance compared to digital morphometric analysis of liver biopsy in chronic hepatitis C.

Vibration-controlled transient elastography (VCTE) is widely used for noninvasive fibrosis staging in chronic hepatitis C. However, internal validation is based solely on variability and success rate and lacks reproducible quality indicators. We analysed the graphic representation of shear wave propagation in comparison with morphometric results of liver biopsy, eliminating observer variability bias. Individual elastograms were classified according to two morphologic criteria: extension of wave propagation (length of the graphic representation) and shear wave dispersal (level of parallelism displayed in the elastogram). Then, a score based on these criteria stratified the elastogram in classes I through III (highest to lowest technical quality). Liver stiffness results of each measurement were compared with collagen contents in liver biopsy by morphometric analysis. A total of 3243 elastograms were studied (316 patients). Digital morphometry in liver biopsy showed significant fibrosis in 66% of samples and advanced fibrosis in 31%. Elastogram quality analysis resulted in 1438 class I measurements (44%), 1070 class II (34%) and 735 class III. Area under the receiver operating curve (AUROC) for severe fibrosis according to class (I, II and III) was 0.941, 0.887 and 0.766, respectively. For advanced fibrosis, AUROCs were 0.977, 0.883 and 0.781, respectively. Spearman's correlation testing for all classes and levels of fibrosis demonstrated significant independent association (r2  = -.95, P < .01). Our study is the first to propose measurable quality criteria for VTCE and to validate them against objective assessment of liver biopsy through digital morphometric imaging analysis. We concluded that VCTE performance is significantly influenced by quality assessment of individual measurements. Considering these criteria in clinical practice may improve accuracy.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4): A single-center study.

Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV) as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD) patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb) and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR) for both HCV and hepatitis B virus (HBV), serum hyaluronic acid level, and alpha-fetoprotein (AFP). Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1%) and diabetic nephropathy (18.7%). HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1%) who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9%) had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA) level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619); also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970). Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

Acoustic Radiation Force Impulse (ARFI) Elastography and Serological Markers in Assessment of Liver Fibrosis and Free Portal Pressure in Patients with Hepatitis B.

BACKGROUND The aim of this study was to investigate the feasibility of using acoustic radiation force impulse (ARFI) elastography, AST-to-platelet ratio index (APRI), and FIB-4 in assessing liver fibrosis and free portal pressure in patients with hepatitis B. MATERIAL AND METHODS We enrolled 126 patients with hepatitis B who underwent liver surgery at the General Surgery Department of the First Affiliated Hospital of Shihezi University Medical School from February 2013 to August 2015. Preoperatively, shear wave velocity (SWV) of the liver was measured with the Siemens S2000 ultrasound system to reflect liver stiffness. Serological markers were collected and fibrosis indices APRI and FIB-4 were calculated. Intraoperatively, liver tissues were harvested and free portal pressure (FPP) was measured. Postoperatively, fibrosis of liver tissues was pathologically staged. RESULTS The results of SWV, APRI, FIB-4, and FPP were all correlated with the degree of liver fibrosis (Spearman correlation coefficients: r=0.777, P<0.001; r=0.526, P<0.001; r=0.471, P<0.001; p<0.000; r=0.675, p<0.000). Receiver operating characteristic curve (ROC) analysis showed that the areas under the curve (AUC) of ARFI, APRI, and FIB-4 in diagnosing liver fibrosis were 0.830, 0.768, and 0.717, respectively, for stage F≥1; 0.861, 0.773, and 0.754, respectively, for stage F≥2; 0.941, 0.793, and 0.779, respectively, for stage F≥3; and 0.945, 0.783, and 0.754, respectively, for stage F=4. SWV, APRI, and FIB-4 were all correlated with FPP (Pearson correlation coefficients: 0.387, P<0.001; 0.446, P<0.001; 0.419, P<0.001). CONCLUSIONS ARFI, APRI, and FIB-4 can assess liver fibrosis in patients with hepatitis B when assessing the portal venous pressure. The difference in diagnostic efficacy between the 3 was not significant.

Cost-effectiveness of enhanced liver fibrosis test to assess liver fibrosis in chronic hepatitis C virus and alcoholic liver disease patients.

AIM: To assess liver fibrosis (LF) in hepatitis C virus (HCV) and alcoholic liver disease (ALD), estimate health outcomes and costs of new noninvasive testing strategies. METHODS: A Markov model was developed to simulate LF progression in HCV and ALD for a cohort of 40-year-old men with abnormal levels of transaminases. Three different testing alternatives were studied: a single liver biopsy; annual Enhanced liver fibrosis (ELF™) followed by liver stiffness measurement (LSM) imaging as a confirmation test if the ELF test is positive; and annual ELF test without LSM. The analysis was performed from the perspective of a university hospital in Spain. Clinical data were obtained from published literature. Costs were sourced from administrative databases of the hospital. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In HCV patients, annual sequential ELF test/LSM and annual ELF test alone prevented respectively 12.9 and 13.3 liver fibrosis-related deaths per 100 persons tested, compared to biopsy. The incremental cost-effectiveness ratios (ICERs) were respectively €13400 and €11500 per quality-adjusted life year (QALY). In ALD, fibrosis-related deaths decreased by 11.7 and 22.1 per 100 persons tested respectively with sequential ELF test/LSM and annual ELF test alone. ICERs were €280 and €190 per QALY, respectively. CONCLUSION: The use of the ELF test with or without a confirmation LSM are cost-effective options compared to a single liver biopsy for testing liver fibrosis in HCV and ALD patients in Spain.

Assessment of liver fibrosis with acoustic radiation force impulse imaging versus liver histology in patients with chronic hepatitis C: a pilot study.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) involves the mechanical excitation of tissues using short-duration acoustic pulses to generate localized displacements in tissue. The displacements results in shear-wave propagation, tracked by ultrasonography (US) correlation-based methods and recorded in meters per seconds. AIM: To compare (ARFI) integrated into a conventional US with the standard histological examination of liver biopsy specimens for the assessment of liver fibrosis. MATERIALS AND METHODS: Histological fibrosis staging with standard liver biopsy using the Metavir scoring system as well as fibrosis assessment using ARFI were performed to 80 patients with chronic hepatitis C over a 3-month period. RESULTS: ARFI findings were identical to the biopsy findings in 61 (76.25%) patients.Fifty-eight (67.5%) patients with an early fibrosis stage (F0, F1, and F2) by histology had identical fibrosis stages using ARFI.Only 20 out of 26 patients with an advanced fibrosis stage (F3 and F4) using ARFI had advanced fibrosis histologically. In the advanced fibrosis stages, the sensitivity of ARFI was 70% and specificity was 80%, with positive and negative predictive values of 53.8 and 88.9%, respectively. The accuracy of detection of advanced fibrosis by ARFI was 77.5%. CONCLUSION: ARFI imaging is a promising noninvasive US-based method for the assessment of liver fibrosis.

Non-invasive assessment of liver fibrosis in patients with hepatitis C: Shear wave elastography and colour Doppler velocity profile technique versus liver biopsy.

BACKGROUND AND STUDY AIMS: Determination of the presence and degree of liver fibrosis is essential for the prognosis and treatment of patients with chronic hepatitis C. Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. We determined the efficacy of shear wave elastography (SWE) and colour Doppler velocity as non-invasive methods for the assessment of liver fibrosis compared to liver biopsy among patients with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: In total, 117 patients with chronic HCV infection and 50 healthy age- and sex-matched control subjects were included. For each patient and control, abdominal ultrasonography, Doppler ultrasonography of the right portal vein (PV), and SWE were performed, whereas liver biopsy was performed for patients. RESULTS: The mean value of the right PV maximum velocity was lower in patients with different stages of fibrosis than in controls (p<0.001). The mean value of liver stiffness determined by SWE was significantly higher in patients with different stages of fibrosis than in controls. Cutoff values for liver stiffness determined by SWE for assessing fibrosis stages were F2⩾4.815, F3⩾6.335, and F4=7.540 with a sensitivity of 84.6%, 96.2%, and 100.0%; specificity of 88.5%, 93.8%, and 100.0%; positive predictive value (PPV) of 93.6%, 98.0%, and 100.0%; negative predictive value (NPV) of 74.2%, 88.2%, and 100.0%; and overall accuracy of 85.9%, 95.6%, and 100.0% [area under the ROC curve (AUC): 0.89, 0.96, and 1.0], respectively. Cutoff values for the right PV maximum velocity for assessing fibrosis stages were F2<23.4, F3<21, and F4<20 with a sensitivity of 65.0%, 57.4%, and 57.1%; specificity of 59.8%, 76.4%, and 75.5%; PPV of 33.8%, 58.3%, and 32.0%; NPV of 84.4%, 75.7%, and 89.7%; and overall accuracy of 61.1%, 69.5%, and 72.5% (AUC: 0.614, 0.696, and 0.625), respectively. CONCLUSION: SWE is effective for the non-invasive assessment of liver fibrosis in patients with HCV infection. SWE provides a more accurate correlation with liver fibrosis stage than colour Doppler velocity profile for the assessment of liver fibrosis, especially in advanced stages (F3 and F4).

Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

PURPOSE: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. METHODS: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. RESULTS: Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. CONCLUSION: Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.

Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant.

UNLABELLED:  Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. RESULTS: Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. CONCLUSION: ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.