Non-invasive Assessment Of Liver Fibrosis Research Articles

Variability of Liver Shear Wave Measurements Using a New Ultrasound Elastographic Technique.

A new 2-dimensional (2D) shear wave elastographic (SWE) device has been developed for the noninvasive assessment of liver fibrosis. Guidelines on measurement acquisition parameters are not yet well established for this technique. Our study aimed to assess 2D SWE measurement variability and to determine the number of measurements required per patient to reliably assess liver stiffness. Two-dimensional SWE was assessed in 55 patients with mixed-etiology chronic liver disease on an Aplio 500 ultrasound system (Toshiba Medical Systems Corporation, Tochigi, Japan). Ten measurements were obtained per patient by an operator blinded to all preceding readings. Results were analyzed with clinical information obtained from medical records. The median interquartile range/median ratio for 2D SWE was 0.131 (quartiles 1-3, 0.089-0.174). Five readings provided an approximation within 0.11 m/s, or 4.2% of the median velocity of 10 measurements. Factors associated with increased measurement variability included body mass index (ρ = 0.388; P = .01), increased skin-to-liver capsule distance (ρ = 0.426; P = .002), and measurements taken within 1.5 cm of the liver capsule (P < .001). Measurements with heterogeneous shear wave profiles (indicated by a region of interest [ROI] SD/speed ratio > 0.15) showed greater deviation from the set's median velocity than those with an ROI SD/speed ratio of 0.15 or lower (0.42 versus 0.22 m/s; P = .001). Two-dimensional SWE showed low overall measurement variability, with a minimum of 5 readings providing equivalent precision to the existing method using 10 samples. Obesity, increasing abdominal wall thickness, subcapsular measurements and an ROI SD/speed ratio of greater than 0.15 were all associated with increased measurement variability. The ROI SD/speed ratio warrants further evaluation as a quality assessment metric, to allow objective operator assessment of individual 2D SWE measurement reliability in real time.

Intra-Individual Comparison between 2-D Shear Wave Elastography (GE System) and Virtual Touch Tissue Quantification (Siemens System) in Grading Liver Fibrosis

Ultrasound-based shear wave elastography (SWE) has recently gained substantial attention for non-invasive assessment of liver fibrosis. The purpose of this study was to perform an intra-individual comparison between 2-D shear wave elastography (2-D-SWE with a GE system) and Virtual Touch Tissue Quantification (VTTQ with a Siemens system) to assess whether these can be used interchangeably to grade fibrosis. Ninety-three patients (51 men, 42 women; mean age, 54 y) with liver disease of various etiologies (hepatitis B virus = 47, hepatitis C virus = 22; alcohol = 6, non-alcoholic steatohepatitis = 5, other = 13) were included. Using published system-specific shear wave speed cutoff values, liver fibrosis was classified into clinically non-significant (F0/F1) and significant (≥F2) fibrosis. Results indicated that intra-modality repeatability was excellent for both techniques (GE 2-D-SWE: intra-class correlation coefficient = 0.89 [0.84–0.93]; VTTQ: intra-class correlation coefficient = 0.90 [0.86–0.93]). Intra-modality classification agreement for fibrosis grading was good to excellent (GE 2-D-SWE: κ = 0.65, VTTQ: κ = 0.82). However, inter-modality agreement for fibrosis grading was only fair (κ = 0.31) using published system-specific shear wave speed cutoff values of fibrosis. In conclusion, although both GE 2-D-SWE and Siemens VTTQ exhibit good to excellent intra-modality repeatability, inter-modality agreement is only fair, suggesting that these should not be used interchangeably.

Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT).

A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7.4±3.2kPa and the mean LIC was 4.81±3.82mg/gdw (n=99). Data available at 4±1.5years showed a significant reduction in LSM (6.6±3.2kPa, p 0.017) and hepatic siderosis measured by LIC (3.65±3.45mg/gdw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurement (n=41) and subjects treated with a stable dose of deferasirox over the entire period of observation (n=39). A reduction of LSM, yet not statistically significant, was achieved in patients on combined deferoxamine + deferiprone, while the group on deferoxamine (n=11) remained stable over time. HCV-RNA positivity was found in 33 patients at T0, 20 of which were treated during the observation period. Patients who underwent anti-HCV therapy showed a more evident reduction in LSM (9±3 vs 7±3.1kPa, p 0.016). Adequate chelation therapy is mandatory in order to prevent liver disease progression in TDT. Patients could benefit from regular non-invasive assessment of liver fibrosis by TE to indirectly monitor treatment adequacy and therapeutic compliance.

Non-invasive Assessment of Liver Fibrosis with ElastPQ: Comparison with Transient Elastography and Serologic Fibrosis Marker Tests, and Correlation with Liver Pathology Results

We investigated the feasibility of using ultrasound shear wave elastography point quantification (ElastPQ) for liver fibrosis staging and compared it with other non-invasive tools with respect to efficacy in liver stiffness measurement. A total of 106 patients who underwent liver stiffness measurements, using ElastPQ and biochemical investigations, before parenchymal liver biopsy or surgery were included. Among these, 51 also underwent transient elastography (TE). Correlations of ElastPQ, TE and aspartate aminotransferase-to-platelet ratio index (APRI) with histopathological findings (as the reference standard) were determined using Spearman's correlation coefficient. The diagnostic performance of ElastPQ, TE and APRI was evaluated using receiver operating characteristic (ROC) curve analysis. ElastPQ had good diagnostic accuracy in identifying each liver fibrosis stage, with an area under the ROC curve (AUC) of 0.810 to 0.864. Stiffness values obtained using ElastPQ, TE and APRI were significantly positively correlated (r = 0.686, r = 0.732 and r = 0.454, respectively) with histologic fibrosis staging (p < 0.001). According to the AUC for the diagnosis of significant fibrosis (≥F2) and cirrhosis (=F4), ElastPQ had better diagnostic accuracy (AUC = 0.929 and 0.834, respectively) than APRI (AUC = 0.656 and 0.618, respectively) (p < 0.05), and was similar to TE (AUC = 0.915 and 0.879, respectively). ElastPQ is a promising ultrasound-based imaging technique for evaluation of liver fibrosis, with a diagnostic accuracy comparable to that of TE.

Non-invasive liver fibrosis assessment and HCV treatment initiation within asystematic screening program in HIV/HCV coinfected patients.

SummaryBackground and aimHepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV).MethodsThe FIB-4 was calculated in all HIV/HCV from 2014–2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of </≥1.45 (established cut-off for ruling out ADVFIB) and SIGFIB/ADVFIB were defined by liver stiffness >7.1 kPa/>9.5 kPa, respectively.ResultsAmong 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43).In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4 <1.45 underwent TE. Interestingly, 40% (23/57) and 18% (10/57) of these patients showed SIGFIB or even ADVFIB, respectively, and 78% (18/23) finally received interferon-free treatment. Overall, only 20% (42/210) of HIV/HCV received interferon-free treatment.ConclusionFIB-4 was not useful for ruling out SIGFIB/ADVFIB in our cohort of HIV/HCV. Treatment was initiated only in a small proportion (20%) of HIV/HCV during the first 2 years of interferon-free treatment availability, although the observed proportion of patients with SIGFIB (assessed by TE) was considerably higher (58%). Thus, it requires the ongoing combined efforts of both HIV and HCV specialists to increase treatment uptake rates in this special population.Electronic supplementary materialThe online version of this article (doi: 10.1007/s00508-017-1231-x) contains supplementary material, which is available to authorized users.

Evaluation of eLIFT for Non-invasive Assessment of Liver fibrosis and Cirrhosis in Patients with Chronic Hepatitis B Virus Infection

Recently, the easy Liver Fibrosis Test (eLIFT), a sum of points attributed to age, gender, gamma-glutamyl transpeptidase, aspartate transaminase, platelets, and prothrombin time, was developed for diagnosing advanced fibrosis and cirrhosis in chronic liver disease. We aimed to evaluate the performance of eLIFT to predict liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). Histologic and laboratory data of 747 CHB patients were analyzed. The performance of eLIFT for diagnosing liver fibrosis and cirrhosis was compared with that of aspartate transaminase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4). To predict advanced fibrosis, the AUROC of eLIFT was comparable with that of APRI (0.66 vs 0.71, p = 0.095) and FIB-4 (0.66 vs 0.67, p = 0.612). To predict severe fibrosis, the AUROC of eLIFT was lower than that of APRI (0.65 vs 0.83, p < 0.001) and FIB-4 (0.65 vs 0.82, p < 0.001). To predict cirrhosis, the AUROC of eLIFT was also lower than that of APRI (0.64 vs 0.85, p = 0.001) and FIB-4 (0.64 vs 0.76, p = 0.033). The eLIFT is not a good non-invasive test for the diagnosis of liver fibrosis and cirrhosis in CHB patients.

Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey

ObjectiveGuidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of...

Non-invasive assessment of liver fibrosis in patients with HBV-related chronic liver disease undergoing antiviral treatment: A preliminary study

In chronic hepatitis B (CHB) patients, fibrosis assessment during antiviral treatment is a key step in the clinical management. Aim of this study was to evaluate the performance of elastography in assessing fibrosis stage in CHB before and after two years of nucleoside/nucleotide analogues (NUC) treatment in comparison with indirect serum markers. CHB diagnosis was made according to standard criteria. A clinical and virological evaluation was performed at baseline and again at 3, 6, 9, 12 18, and 24 months during treatment. Fibrosis was evaluated by liver biopsy, elastography and indirect serum markers. Of 75 patients, 50 had CHB, HBeAg negative and were deemed eligible for this study. Of these, 22 underwent liver biopsy. Mean histo-morphometric values of fibrotic tissue differed significantly in the stage < S3 vs. stage ≥S3: 2.01±2.62% vs. 12.85±7.31% (p=0.03), respectively. At 18 and 24 months, stiffness values were statistically reduced from those previously observed (P=0.03 and P<0.001). At 24 months the values of APRI, FIB-4 and LOK were not different from baseline values, while the value of FORNS score at 24 months was the only one statistically reduced. In two patients with fibrosis stage S3 and S6, respectively, fibrosis regressed to stage S2 and S5. In conclusion, the results of the present study show that liver histology, stiffness and FORNS score improve significantly during a long-term follow-up of HBV patients successfully treated with NUC. These results strongly suggest that the non-invasive evaluation of liver fibrosis represents a key step in the management and treatment of chronic HBV hepatitis.

The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease

Background/AimThe gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a novel serum model, which was reported more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD).ResultsOf 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GPR was higher than that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89 vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p = 0.104).Materials and Methods131 patients with CHB-NAFLD were included, and the diagnostic performances of GPR, APRI and FIB-4 were compared by receiver operating characteristic (ROC) curves and the area under ROC curves (AUROCs).ConclusionsThe GPR could be used as a non-invasive marker to predict liver fibrosis and cirrhosis in CHB-NAFLD individuals.

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 aimsDetermination 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 methodsIn 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. ResultsThe 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. ConclusionSWE 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).

P417 Non-invasive assessment of liver fibrosis by transient elastography and AST to ALT ratio in patients with Crohn's disease treated with methotrexate

Background: One of the most feared concerns about the use of methotrexate (MTX) is the risk of developing chronic liver injury. Transient elastography is a simple, non-invasive method for estimating liver fibrosis. AST to ALT ratio (AST/ALT ratio) is also a good easy-to-use indicator of the risk of fibrosis in chronic liver diseases. The aim was to assess the risk of chronic liver injury induced by MTX in a cohort of patients with Crohn's disease (CD) at a high-volume tertiary center. Methods: Cross-sectional study including CD patients treated with methotrexate. Clinical and laboratorial data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®, and the cutoff values for significant liver fibrosis (according to METAVIR) was F ≥2: 7.1 kPa. AST/ALT ratio was considered significant for risk of fibrosis if >1. Patients with chronic hepatitis B or C, excessive daily consumption of alcoholic, non-alcoholic steatohepatitis, or other known causes of chronic liver disease were excluded. Estimates of the presence and severity of steatosis according to the parameter of controlled attenuation (CAP) were also evaluated, considering the absence of significant steatosis (S0) if less than 200 dB/m, mild (S1) if 200–249 dB/m, moderate (S2) if 250–299 dB/m, and severe (S3) if 300 dB/m or greater. Results: 62 patients were included, 35 female (56.5%), with a mean age of 37.5±11.3 years. MTX was the first-line immunosuppressant in 9 patients (14.5%). Indications for initiating MTX included: adjuvant to anti-TNF agent (43.5%), intolerance to azathioprine (27.4%), corticodependence (19.4%) and corticoresistance (9.7%). Mean treatment duration was 88±86 weeks. Mean cumulative MTX dose was 998±871 mg. All patients received MTX subcutaneously. In sixteen patients MTX was discontinued due to changes in liver function tests. The mean value of Fibroscan was 5.3±1.5 kPa, and in 11.1% of cases the value was considered significant for fibrosis (≥7.1 kPa). In none of the cases was a value compatible with METAVIR F4 (>11 kPa). The mean CAP value was 198±58 dB/m, distributed as follows: S0 63.3%, S1 16.7%, S2 13.3% and S3 6.7%. The mean AST/ALT ratio was 1.12±0.43 and was considered significant (>1) in 58.7% of the cases. Fibroscan values correlated directly with ALT (0.44, p=0.026) and bilirubin (0.426, p=0.038), but not with duration of treatment or cumulative dose. Likewise, these variables did not correlate with the AST/ALT ratio. Conclusions: Excluding patients with other risk factors for chronic liver disease, the use of methotrexate regardless of the cumulative dose appears to be safe in the medium to long term in CD patients according to non-invasive methods.

THU-488 - Noninvasive assessment of liver fibrosis and portal hypertension after viral eradication in post-transplant hepatitis C

THU-488 - Noninvasive assessment of liver fibrosis and portal hypertension after viral eradication in post-transplant hepatitis C

Ultrasound Elastography: Review of Techniques and Clinical Applications.

Elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. These techniques take advantage of changed soft tissue elasticity in various pathologies to yield qualitative and quantitative information that can be used for diagnostic purposes. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave). Ultrasound-based methods are of particular interest due to its many inherent advantages, such as wide availability including at the bedside and relatively low cost. Several ultrasound elastography techniques using different excitation methods have been developed. In general, these can be classified into strain imaging methods that use internal or external compression stimuli, and shear wave imaging that use ultrasound-generated traveling shear wave stimuli. While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging.Here, we review the basic principles, foundation physics, and limitations of ultrasound elastography and summarize its current clinical use and ongoing developments in various clinical applications.

Tegafur-uracil-induced rapid development of advanced hepatic fibrosis.

Tegafur-uracil has been reported to have only minor adverse effects and is associated with liver injury in 1.79% of Japanese patients. The development of tegafur-uracil-induced hepatic fibrosis with portal hypertension is rare. Here, we report a case of a 74-year-old woman with rapidly developing tegafur-uracil-induced hepatic fibrosis. The patient had no history of liver disease and had been treated with tegafur-uracil for 8 mo after breast cancer surgery. The patient was admitted to our hospital for abdominal distension and leg edema associated with liver dysfunction. Computed tomography imaging revealed massive ascites and splenomegaly, and a non-invasive assessment of liver fibrosis indicated advanced fibrosis. The histopathological findings revealed periportal fibrosis and bridging fibrosis with septation. The massive ascites resolved after discontinuing tegafur-uracil. These findings suggest that advanced hepatic fibrosis can develop from a relatively short-term administration of tegafur-uracil and that non-invasive assessment is useful for predicting hepatic fibrosis.

THU-494 - Non-invasive assessment of liver fibrosis by point share wave elastography in primary biliary cholangitis: comparison with fibroscan® and fibrosis scores

THU-494 - Non-invasive assessment of liver fibrosis by point share wave elastography in primary biliary cholangitis: comparison with fibroscan® and fibrosis scores

Alcohol use, viral hepatitis and liver fibrosis among HIV‐positive persons in West Africa: a cross‐sectional study

Introduction: Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub-Saharan Africa. Methods: The study was undertaken in three HIV referral clinics in Côte d’Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non-invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase-to-platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)-C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti-hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results: A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36–50). Their median CD4 count was 393 cells/mm3 (IQR: 234–563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8–6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT-C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2–14.0), (Ref. AUDIT-C <4) and HBV infection (OR = 2.9, CI: 1.2–7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir-based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients.

Correlation Between Fibroscan and ARFI with Metavir Liver Fibrosis Score

Non-invasive assessment of liver fibrosis with Fibroscan and acoustic radiation force impulse (AFRI) imaging are two most popular modalities to measure liver fibrosis. Fibroscan is a well-established modality which measure both liver fibrosis and steatosis. However, there is considerable failure rate, and without image quidding the data may be misleading in the present of focal lesion in R hepatic lobe. ARFI may select an optimal location for measurement but there are concerns on the inter-observer and inter-location variations. We try to decrease the variation by measuring ARFI at two different locations. In a consecutive series of patients who received liver histology study were prospectively enrolled. All participant received hemogram, liver biochemistry, viral markers, ARFI and Fibroscan within 4 weeks of histology study. A standardized protocol was used to both Fibroscan and ARFI on the same day by a single technologist. Then both data from Fibroscan and ARFI were correlated with liver histology. Additional series of non-biopsy cases with chronic hepatitis B, chronic hepatitis C and non-alcoholic liver disease were also included for validation analysis. A total of 83 patients with liver histology study were included. This series included 34 NonB and NonC, 8 autoimmune liver diseases, 29 chronic hepatitis B and 12 hepatitis C. We excluded patients with alcoholism, dual HBV and HCV infection and unknown etiology. The correlation between Fibroscan and ARFI two-location measurement is good (R2=0.589, P<0.001). The area under the curve for Metavir 4 fibrosis are 0.877 and 0.919 for Fibroscan and ARFI respectively. A relatively lower value in Fibroscan than in ARFI is noted in the present of severe steatosis (CAP≥293, P<0.001). Similar situation was found in non-biopsy patients received both studies. The phenomenon of lower slope in patients with high CAP value are presented in all HBV, HCV or NBNC non-biopsy groups. We conclude that the correlation between Fibroscan and ARFI two location measurement is good. ARFI tends to have a better linearity with histology fibrosis grades than Fibroscan in patients with severe steatosis.

Progression of Liver Fibrosis Can be Controlled Under Adequate Chelation in Transfusion-Dependent Thalassemia (TDT).

BACKGROUND. A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection have been implicated in the development of liver fibrosis. The objective of iron chelation is to avoid the complications of siderosis, such as hepatocellular injury. As a matter of fact, adequate chelation therapy is mandatory in order to prevent liver disease progression. In the last few years the availability of different chelating agents (coupled with anti-HCV therapy) allowed control of liver disease due to secondary iron overload. Transient elastography (TE, Fibroscan®) is a non-invasive and rapid diagnostic tool that enables accurate prediction of hepatic fibrosis by measuring liver stiffness (LSM). Patients with TDT could benefit from regular non-invasive assessment of liver fibrosis as an indirect indicator of treatment adequacy and therapeutic compliance.AIM. We investigated the efficacy of adequate iron chelation to prevent the progression of liver fibrosis in TDT patients over a time period of approximately 4 years.MATERIALS AND METHODS. We analysed data in a retrospective cohort study over a 4±1.5-year time period. Ninety-nine patients with beta-thalassemia major (41 M, 58 F, aged 36±6 years), followed at Rare Disease Center, Ca’ Granda Hospital in Milan, were enrolled in the study. All patients received regular transfusions every 2-4 weeks. Chelation therapy was registered using deferasirox (DFX), deferoxamine (DFO), deferiprone (DFP) or a combination of the three. All the participants underwent TE and T2-weighted magnetic resonance imaging (T2*MRI) twice (at baseline,T0 and after approximately 4 years, T1). Liver iron concentration (LIC) was assessed by T2*MRI using the appropriate formula at T0 and T1. LSM was measured according to the following cut-off: <5.0 kPa no fibrosis (F0), 5.1-7.9 kPa mild fibrosis (F1), >7.9 kPa moderate fibrosis (F2), >10.3 advanced fibrosis (F3), >11.9 kPa cirrhosis (F4). We divided our cohort into groups depending on the administered chelating agent and the presence of iron overload defined by a LIC > 4.23 mg Fe/g dry weight (corresponding to a T2* value > 6.3 ms).RESULTS. At baseline the mean pre-transfusion Hb levels was 9.74 ± 1.17 g/dL, the mean iron intake 0.33 ± 0.07 mg Fe/kg/d and median serum ferritin 669.5 ng/ml (range 113-5912). HCV-RNA positivity was found in 33 patients (33%) at T0: 20 patients were treated for hepatitis C during the observation period. The overall mean LSM was 7.4±3.2 kPa, the mean hepatic T2* was 9.92±7.01 ms and the mean LIC was 4.81±3.82 mg/g dw (n=99). Data available at 4±1.5 years showed a significant reduction in liver stiffness (6.6±3.2 kPa, p 0.017), iron overload measured by hepatic T2* (12.84±7.28 ms, p < 0.001) and LIC (3.65±3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurment (n=41). The number of patients with moderate to advanced fibrosis (LSM ≥ F2) decreased, yet not significantly (30% vs 19%, p 0.07). Subjects treated with a stable dose of DFX over the entire period of observation (n=39) showed a reduction of LSM (6.9±2.3 vs 6.06±2.4, p 0.04) and a concomitant improvement of hepatic T2* and LIC values (respectively 11.02±6.57 vs 15.04±6.42 and 3.84±2.81 vs 2.49±1.89, p < 0.001). In this group we observed a substantial decrease in the number of patients with LIC > 4.23 mg Fe/g dw (33% vs 13%, p 0.01). A reduction of LSM, yet not statistically significant due to the limited size of the cohort, was achieved in patients on combined DFO+DFP at T0 and T1 (n=6, 8.6±5.5 vs 7.3±3.8). The group of patients on DFO (n=11) remained stable over time. Patients who underwent anti-HCV therapy showed an even more evident reduction in LSM (9±3 vs 7±3.1, p 0.016).CONCLUSION. These data support evidence on the efficacy of adequate iron chelation therapy and, if necessary, anti-HCV treatment in decreasing or at least controlling the progression of liver fibrosis measured by TE in transfusion-dependent BTM patients. Therapeutic compliance and tailoring of drugs is essential to prevent hepatic injury resulting from siderosis. Moreover, proper chelation and treatment of HCV infection act sinergistically to limit progression of liver disease in TDT patients with active hepatitis C, so that development of cirrhosis could be either prevented or greatly delayed. DisclosuresCappellini:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme-Sanofi: Membership on an entity's Board of Directors or advisory committees.

Comparison of Two-Dimensional Shear Wave Elastography and Real-Time Tissue Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B

Background: Noninvasive assessment of liver fibrosis has important clinical significance. Different techniques including two-dimensional shear-wave elastography (2D SWE) and real-time tissue elastography (RTE) are reported to be useful for the noninvasive diagnosis of hepatic fibrosis. All these techniques are affected by many factors. How to choose a reasonable method needs further studies. Purpose: This study was conducted to comparatively assess the diagnostic performance of 2D SWE and RTE in patients with Chronic Hepatitis B (CHB) and influence of inflammation on the stiffness values obtained by both techniques, so as to objectively assess the reasonable choice between these 2 elastography techniques for noninvasive assessment of hepatic fibrosis in clinical practice. Materials and Methods: Four-hundred and thirty-seven patients with CHB meeting the inclusion criteria were enrolled in the study. All patients underwent liver stiffness measurements by using 2D SWE and RTE on the same day. Histologic fibrosis was staged and inflammation activity was graded based on the METAVIR scoring system on liver biopsy specimens. Results: The liver stiffness values by using 2D SWE and RTE both increased in parallel with the degree of liver fibrosis and the grade of inflammation. However, the diagnostic efficacy of significant fibrosis and cirrhosis using 2D SWE was significantly higher than that of RTE. The 2D SWE measurement values were statistically different in different alanine aminotransferase (ALT) levels and METAVIR activity grades; however, no statistically significant differences were observed by using RTE. The diagnostic efficacy of 2D SWE significantly varied with elevated ALT levels compared with RTE. Conclusion: 2D SWE was more accurate than RTE in the assessment of significant fibrosis and cirrhosis in patients with CHB. Compared with RTE, the measurement values and diagnostic performance obtained by 2D SWE were prone to be more easily affected by the inflammation fluctuations.

Early changes in non-invasive assessment of liver fibrosis in hepatitis C virus-infected patients treated with DAAs: Preliminary reports

Early changes in non-invasive assessment of liver fibrosis in hepatitis C virus-infected patients treated with DAAs: Preliminary reports