Ultrasound-based Transient Elastography Research Articles

Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis.

Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.

Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia.

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology.

Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway.

Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2-4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4 <1·3, BARD score 0-1, NAFLD fibrosis score less than -1·455, AST to ALT ratio <0·8, and APRI <0·5). We also assessed independent factors associated with that discordance by multivariable logistic regression analysis. We included 1202 people with HIV at risk for NAFLD (mean age 51·2 years [SD 10·1], 914 [76%] male and 288 [24%] female, mean HIV duration 16·3 years [SE 9·7], mean BMI 26·5 Kg/m2 [SD 4·5]; prevalence of diabetes 49·5%). 222 (18·5%) of these participants had significant liver fibrosis according to transient elastography. Assessment of simple fibrosis biomarkers would have decreased transient elastography referrals between 22·5% (BARD score) and 82·4% (APRI). Discordance rate ranged from 3·9% (NAFLD fibrosis score) to 11·1% (APRI). After adjustment for age, sex, presence of diabetes, level of HDL cholesterol, and CD4 cell count, BMI (odds ratio 1·12, 95% CI 1·07-1·17) and triglyceride level (1·25, 1·08-1·46) were independent predictors of discordance for low APRI and high transient elastography. Use of a two-tier pathway to identify liver fibrosis in ageing people with HIV at risk for NAFLD could reduce transient elastography examinations by a substantial proportion, reducing costs and helping to optimise use of resources in HIV care. GS is supported by a Senior Salary Award from Fonds de recherche du Québec-Santé (number 296306).

Quantitative Susceptibility Mapping versus R2*-based Histogram Analysis for Evaluating Liver Fibrosis: Preliminary Results.

The staging of liver fibrosis is clinically important, and a less invasive method is preferred. Quantitative susceptibility mapping (QSM) has shown a great potential in estimating liver fibrosis in addition to R2* relaxometry. However, few studies have compared QSM analysis and liver fibrosis. We aimed to evaluate the feasibility of estimating liver fibrosis by using QSM and R2*-based histogram analyses by comparing it with ultrasound-based transient elastography and the stage of histologic fibrosis. Fourteen patients with liver disease were enrolled. Data sets of multi-echo gradient echo sequence with breath-holding were acquired on a 3-Tesla scanner. QSM and R2* were reconstructed by water-fat separation method, and ROIs were analyzed for these images. Quantitative parameters with histogram features (mean, variance, skewness, kurtosis, and 1st, 10th, 50th, 90th, and 99th percentiles) were extracted. These data were compared with the elasticity measured by ultrasound transient elastography and histological stage of liver fibrosis (F0 to F4, based on the new Inuyama classification) determined by biopsy or hepatectomy. The correlation of histogram parameters with intrahepatic elasticity and histologically confirmed fibrosis stage was examined. Texture parameters were compared between subgroups divided according to fibrosis stage. Receiver operating characteristic (ROC) analysis was also performed. P < 0.05 indicated statistical significance. The six histogram parameters of both QSM and R2*were significantly correlated with intrahepatic elasticity. In particular, three parameters (variance, percentiles [90th and 99th]) of QSM showed high correlation (r = 0.818-0.844), whereas R2* parameters showed a moderate correlation with elasticity. Four parameters of QSM were significantly correlated with fibrosis stage (ρ = 0.637-0.723) and differentiated F2-4 from F0-1 fibrosis and F3-4 from F0-2 fibrosis with areas under the ROC curve of > 0.8, but those of R2* did not. QSM may serve as a promising surrogate indicator in detecting liver fibrosis.

Comparison of Transient Elastography and Liver Biopsy in Assessing Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Ultrasound-based transient elastography (TE) or TE of the liver is a noninvasive tool for effectively evaluating liver stiffness and fibrosis. The study aimed to compare the accuracy of TE as assessed by Fibroscan with liver biopsy in staging fibrosis in patients with NAFLD. Consecutive NAFLD patients (N = 72) were prospectively enrolled. TE evaluation was performed with Fibroscan and compared with liver biopsy, which is a reference standard. Fibrosis was staged according to the METAVIR scoring system (Meta-analysis of Histological Data in Viral Hepatitis). TE scores and biopsy-related fibrosis stages were correlated. Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) of TE was evaluated. Data were analyzed using software R v3.6.3. Liver biopsy showed that 36.11% of patients did not exhibit fibrosis, whereas 25, 16.67, 15.28, and 6.94% of patients had stage F1 (por-tal/mild fibrosis), F2 (periportal/moderate fibrosis), F3 (bridging/severe fibrosis), and F4 (cirrhosis/advanced fibrosis), respectively. TE showed that 50% of patients had cirrhosis, whereas 20.83,15.28, and 13.86% of patients had mild, moderate, and severe fibrosis, respectively. TE had 71% accuracy, 89% sensitivity, and 38% specificity in diagnosing the severity of fibrosis. Hence, it can be implemented as a noninvasive alternative diagnostic tool for understanding the severity of fibrosis in patients with NAFLD. Moreover, it can also be used for quick early diagnosis of NAFLD, reliable staging of fibrosis, and understanding the need for liver transplantation in patients with NAFLD.

Defining values for controlled attenuation parameter and liver stiffness in youth without liver disease.

We aimed to determine the reference values to define an age-specific normal range of controlled attenuation parameter (CAP, a measure of liver steatosis) and liver stiffness measurement (LSM) values assessed by ultrasound-based transient elastography in adolescents without underlying liver disease. A total of 462 participants were included in this cross-sectional study using data from NHANES 2017-2018. LSM and CAP were carried out using the FibroScan® M-probe. Anthropometric, metabolic and hematological parameters were measured. The median CAP was 199.0 dB/m (150.0-245.0 dB/m, 10th to 90th percentiles) and the median LSM was 4.7 kPa (3.4-6.3 kPa, 10th to 90th percentiles) for ages 12-19.9 years. Regression analyses show that the CAP and LSM were not positively correlated with age (boys CAP R2 = 0.001, p = 0.576 and LSM R2 = 0.012, p = 0.096; girls CAP R2 = 0.011, p = 0.113 and LSM R2 = 0.006, p = 0.236). Finally, CAP was positively associated with LSM in girls (β = 0.189, p = 0.005) but not in boys (β = -0.083, p = 0.202). The reference values indicated here for LSM and CAP will help in the screening of adolescents between ages 12 and 19.9 years and might serve as a useful method for identifying those youth at high risk of nonalcoholic fatty liver disease. The reference values indicated in this study for liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) will help in the screening of adolescents between ages 12 and 19.9 years in clinical practice. The cutoffs of LSM and CAP might serve as a useful method for identifying those youth at high risk of nonalcoholic fatty liver disease.

Increased Hepatic Fat Content in Patients with Resistance to Thyroid Hormone Beta.

Background: Thyroid hormone (TH) has important functions in controlling hepatic lipid metabolism. Individuals with resistance to thyroid hormone beta (RTHβ) who harbor mutations in the THRB gene experience loss-of-function of thyroid hormone receptor beta (TRβ), which is the predominant TR isoform expressed in the liver. We hypothesized that individuals with RTHβ may have increased hepatic steatosis. Methods: Controlled attenuation parameter (CAP) was assessed in individuals harboring the R243Q mutation of the THRB gene (n = 21) and in their wild-type (WT) first-degree relatives (n = 22) using the ultrasound-based transient elastography (TE) device (FibroScan). All participants belonged to the same family, lived on the same small island, and were therefore exposed to similar environmental conditions. CAP measurements and blood samples were obtained after an overnight fast. The observers were blinded to the status of the patients. Results: The hepatic fat content was increased in RTHβ individuals compared with their WT relatives (CAP values of 263 ± 21 and 218.7 ± 43 dB/m, respectively, p = 0.007). The CAP values correlated with age and body mass index (BMI) (age: r = 0.55, p = 0.011; BMI: r = 0.51, p = 0.022) in the WT first-degree relatives but not in RTHβ individuals, suggesting that the defect in TRβ signaling was predominant over the effects of age and obesity. Circulating free fatty acid levels were significantly higher in RTHβ individuals (0.29 ± 0.033 vs. 0.17 ± 0.025 mmol/L, p = 0.02). There was no evidence of insulin resistance evaluated by the homeostatic model assessment of insulin resistance in both groups studied. Conclusions: Our findings provide evidence that impairments in intrahepatic TRβ signaling due to mutations of the THRB gene can lead to hepatic steatosis, which emphasizes the influence of TH in the liver metabolism of lipids and provides a rationale for the development TRβ-selective thyromimetics. Consequently, new molecules with a very high TRβ affinity and hepatic selectivity have been developed for the treatment of lipid-associated hepatic disorders, particularly nonalcoholic fatty liver disease.

Estimation of liver elasticity using the finite element method and four-dimensional computed tomography images as a biomarker of liver fibrosis.

Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis. Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4). The mean±standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54±0.33mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r=0.87, P<0.001). Furthermore, the estimated whole liver elasticity was statistically significantly correlated with the UTE (r=0.84, P<0.001), APRI score (r=0.62, P=0.005), and FIB-4 score (r=0.54, P=0.021). In this study, liver elasticity was estimated through FEM-based simulation and actual respiratory-induced liver displacement obtained from 4DCT images. Furthermore, we assessed that the estimated elasticity of the liver's right lobe was strongly correlated with the UTE. Therefore, the estimated elasticity has the potential to be a feasible imaging biomarker for assessing liver fibrosis using only 4DCT images without additional inspection or equipment costs. Because our results were derived from a limited sample of 20 patients, it is necessary to evaluate the accuracy of elasticity estimation for each liver segment on larger groups of biopsied patients to utilize liver elasticity information for radiotherapy planning.

Liver stiffness assessment by transient elastography suggests high prevalence of liver involvement in common variable immunodeficiency

BackgroundUp to 50% of patients with common variable immunodeficiency (CVID) present persistently increased serum levels of liver enzymes and/or mild hepatomegaly. Ultrasound-based transient elastography (TE) is largely used for early detection of the progression of chronic liver diseases, but has never been employed in CVID. We performed a cross-sectional study to evaluate TE values in a cohort of adult CVID-patients. MethodsFull blood count, liver function test, liver and spleen sonogram and ultrasound-based TE were performed in 77 adult CVID patients. Demographic and clinical data were retrospectively collected from medical files. Results33.8% (26/77) patients presented increased TE values ranging from moderate fibrosis to cirrhosis. TE values were positively correlated with ALP, γGT, spleen longitudinal diameter and peripheral blood counts (no significant correlation with BMI, AST, ALT, total proteins, albumin, bilirubin and hemoglobin). Moreover, liver stiffness was higher in patients with the clinical phenotypes polyclonal lymphoproliferation and enteropathy, and patients with both these complications had an increased risk (OR: 7.14) of presenting pathologic TE values compared with those without anyone of these. ConclusionsTransient elastography is a useful tool to be used alongside clinical and laboratory data to assess liver involvement in CVID.

Prevalence and Determinants of Significant Liver Fibrosis by Vibration-Controlled Transient Elastography in Thai Chronic Hepatitis B Patients.

Aims To describe the prevalence of significant liver fibrosis by ultrasound-based vibration-controlled transient elastography (VCTE; FibroScan®) and to identify the determinants of significant liver fibrosis in Thai chronic hepatitis B patients. Methods A cross-sectional study of consecutive chronic hepatitis B patients performed VCTE and followed up at Rajavithi Hospital, Bangkok, Thailand, was conducted between 1 January, 2013, and 31 December, 2016. Liver fibrosis was defined as minimal (METAVIR F0-1) by VCTE < 7.2 kPa and significant (METAVIR F2-4) by VCTE ≥ 7.2 kPa. VCTE assessments and medical records were retrospectively reviewed. The prevalence and determinants of significant liver fibrosis were analyzed. Results A total of 206 eligible patients were included; 120 patients (58.3%) were female. The mean age was 50 years (SD 12.4 years), and 32.5% had a body mass index ≥ 25. The prevalences of minimal (F 0-1) and significant fibrosis (F2-4) were 74.3% and 25.7%, respectively. The prevalence of hepatitis B e antigen negative (HBeAg -ve) was 83%. The median serum hepatitis B virus viral load was 4,340 IU/mL (range 20-271,883,036). Significant determinants of significant fibrosis (F2-4) were male gender (aOR 3.24 [95%CI: 1.36-7.72]) and high aspartate transaminase (AST) level (aOR 5.71 [95%CI: 2.03-16.04]). Conclusion Around one-quarter of the Thai patients with chronic viral hepatitis B had significant liver disease defined by VCTE, requiring further evaluation for specific treatment for hepatitis B virus. Determinants of significant liver fibrosis were male gender and high AST level.

Imaging of Hepatic Fibrosis

The purpose of this review is to discuss the current imaging techniques for non-invasive assessment of liver fibrosis (LF). Elastography-based techniques are the most widely used imaging methods for the evaluation of LF. Currently, MR elastography (MRE) is the most accurate non-invasive method for detection and staging of LF. Ultrasound-based vibration-controlled transient elastography (VCTE) is the most widely used as it can be easily performed at the point of care but has technical limitations especially in the obese. Innovations and technical improvements continue to evolve in elastography for improving accuracy and avoiding misinterpretation from confounding factors. Other imaging methods including diffusion-weighted imaging (DWI), hepatocellular contrast-enhanced (HCE) MRI, T1 relaxometry, T1ρ imaging, textural analysis, liver surface nodularity, susceptibility-weighted imaging, and perfusion imaging are promising but need further evaluation and clinical validation. MRE is the most accurate imaging technique for assessment of LF.

Magnetic resonance elastography in the assessment of hepatic fibrosis: a study comparing transient elastography and histological data in the same patients.

To evaluate the quantitative measurement of liver stiffness (LS), compare the diagnostic performance of magnetic resonance elastography (MRE) and ultrasound-based transient elastography (TE), and evaluate two different MRE-based LS measurement methods. Between October 2013 and January 2015, 116 consecutive patients with chronic liver disease underwent MRE to measure LS (kilopascals; kPa). Of the 116 patients, 51 patients underwent both TE and liver biopsy, and the interval between the liver biopsy and both the MRE and TE was less than 90days. MRE-derived LS values were measured on the anterior segment of the right lobe (single small round regions of interest per slice; srROIs) and whole right lobe of the liver (free hand region of interest; fhROI), and these values were correlated with pathological fibrosis grades and diagnostic performance. Pathological fibrosis stage was significantly correlated with srROIs (r=0.87, p<0.001), fhROI (r=0.80, p<0.001), and TE (r=0.73, p<0.001). For detection of significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis, the area under the curve (AUC) associated with the srROIs was largest, and there was a significant difference between srROIs and TE (0.93 vs. 0.82, p=0.006), srROIs and fhROI (0.93 vs. 0.89, p=0.04) for detection of ≥F2. For advanced fibrosis and cirrhosis detection, AUCs were not significant (0.92-0.96). MRE and TE detected liver fibrosis with comparable accuracy. In particular, the srROIs method was effective for detecting of significant fibrosis.

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Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease

Magnetic resonance imaging (MRI) techniques and ultrasound-based transient elastography (TE) can be used in noninvasive diagnosis of fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We performed a prospective study to compare the performance of magnetic resonance elastography (MRE) vs TE for diagnosis of fibrosis, and MRI-based proton density fat fraction (MRI-PDFF) analysis vs TE-based controlled attenuation parameter (CAP) for diagnosis of steatosis in patients undergoing biopsy to assess NAFLD. We performed a cross-sectional study of 104 consecutive adults (56.7% female) who underwent MRE, TE, and liver biopsy analysis (using the histologic scoring system for NAFLD from the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System) from October 2011 through May 2016 at a tertiary medical center. All patients received a standard clinical evaluation, including collection of history, anthropometric examination, and biochemical tests. The primary outcomes were fibrosis and steatosis. Secondary outcomes included dichotomized stages of fibrosis and nonalcoholic steatohepatitis vs no nonalcoholic steatohepatitis. Receiver operating characteristic curve analyses were used to compare performances of MRE vs TE in diagnosis of fibrosis (stages 1-4 vs 0) and MRI-PDFF vs CAP for diagnosis of steatosis (grades 1-3 vs 0) with respect to findings from biopsy analysis. MRE detected any fibrosis (stage 1 or more) with an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% confidence interval [CI], 0.74-0.91), which was significantly higher than that of TE (AUROC, 0.67; 95% CI, 0.56-0.78). MRI-PDFF detected any steatosis with an AUROC of 0.99 (95% CI, 0.98-1.00), which was significantly higher than that of CAP (AUROC, 0.85; 95% CI, 0.75-0.96). MRE detected fibrosis of stages 2, 3, or 4 with AUROC values of 0.89 (95% CI, 0.83-0.96), 0.87 (95% CI, 0.78-0.96), and 0.87 (95% CI, 0.71-1.00); TE detected fibrosis of stages 2, 3, or 4 with AUROC values of 0.86 (95% CI, 0.77-0.95), 0.80 (95% CI, 0.67-0.93), and 0.69 (95% CI, 0.45-0.94). MRI-PDFF identified steatosis of grades 2 or 3 with AUROC values of 0.90 (95% CI, 0.82-0.97) and 0.92 (95% CI, 0.84-0.99); CAP identified steatosis of grades 2 or 3 with AUROC values of 0.70 (95% CI, 0.58-0.82) and 0.73 (95% CI, 0.58-0.89). In a prospective, cross-sectional study of more than 100 patients, we found MRE to be more accurate than TE in identification of liver fibrosis (stage 1 or more), using biopsy analysis as the standard. MRI-PDFF is more accurate than CAP in detecting all grades of steatosis in patients with NAFLD.

From liver biopsy to non-invasive markers in evaluating fibrosis in chronic liver disease

Chronic liver disease is a late stage of progressive hepatic fibrosis. It consists of functional and structural disruptions in most chronic liver diseases. An accurate diagnosis allows us to establish the degree of fibrosis and the stage of the disease, the prognosis of the patient and to predict a treatment response. Despite the fact that liver biopsy is considered a gold standard, noninvasive methods for diagnosing liver fibrosis have gained more and more importance. Whether we talk about serum biomarkers or imagistic methods from transient elastography to 3-D magnetic resonance elastography, the question remains: are these useful or useless? Serum biomarkers represent blood components that can reflect liver histological changes, thus they can monitor the continuous process of fibrosis. These can be subcategorized in direct (that show extracellular matrix turnover) and indirect markers (that reflect disturbances in the hepatic function). However these markers alone are not as accurate in the staging of fibrosis, only help differentiate patients without or with low grade of fibrosis from those with significant fibrosis and cannot be considered alone in the diagnosis of liver fibrosis. Imagistic methods include: ultrasound-based transient elastography, magnetic resonance elastography (MRE), 2D-shear wave elastography, acoustic radiation impulse imaging (ARFI) and cross sectional imaging, the first being the most used. Using a combination of non-invasive tools allows us to diminish the number of patients in need of liver biopsy. However, the patient must always be informed of the advantages and disadvantages of each method and its limitations.

CP-027 Protocolised use of protease inhibitors for hepatitis C in a Health Care Area: 18 months of cost savings

BackgroundIn order to bring prescriptions for the use of direct-acting antiviral agents (DAAs) for the treatment of HCV genotype 1 infection in mono and co-infected patients in line with the...

Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C

To compare the diagnostic accuracy of TE and MRE and establish cutoff levels and diagnostic strategies for both techniques, enabling selection of patients for liver biopsy. One hundred three patients with chronic hepatitis B or C and liver biopsy were prospectively included. Areas under curves (AUROC) were compared for TE and MRE for METAVIR fibrosis grade ≥ F2 and ≥F3. We defined cutoff values for selection of patients with F0-F1 (sensitivity >95%) and for significant fibrosis F2-F4 (specificity >95%). Following exclusions, 85 patients were analysed (65 CHB, 19 CHC, 1 co-infected). Fibrosis stages were F0 (n = 3), F1 (n = 53), F2 (n = 15), F3 (n = 8) and F4 (n = 6). TE and MRE accuracy were comparable [AUROCTE ≥ F2: 0.914 (95% CI: 0.857-0.972) vs. AUROCMRE ≥ F2: 0.909 (0.840-0.977), P = 0.89; AUROCTE ≥ F3: 0.895 (0.816-0.974) vs. AUROCMRE ≥ F3: 0.928 (0.874-0.982), P = 0.42]. Cutoff values of <5.2 and ≥8.9 kPa (TE) and <1.66 and ≥2.18 kPa (MRE) diagnosed 64% and 66% of patients correctly as F0-F1 or F2-F4. A conditional strategy in inconclusive test results increased diagnostic yield to 80%. TE and MRE have comparable accuracy for detecting significant fibrosis, which was reliably detected or excluded in two-thirds of patients. A conditional strategy further increased diagnostic yield to 80%. • Both ultrasound-based transient elastography and magnetic resonance elastography can assess hepatic fibrosis. • Both have comparable accuracy for detecting liver fibrosis in viral hepatitis. • The individual techniques reliably detect or exclude significant liver fibrosis in 66 %. • A conditional strategy for inconclusive findings increases the number of correct diagnoses.

MR elastography of liver disease: State of the art

Hepatic fibrosis is a common result of different chronic liver diseases caused by viral infections, alcohol abuse, nonalcoholic fatty liver disease (NAFLD), autoimmune disease and metabolic/genetic disorders. Hepatic fibrosis is a dynamic process which can, in some cases, be reversible with effective treatment (1, 2). Otherwise, it can progress to more advanced stages including cirrhosis where liver function is impaired and severe complications can occur such as variceal bleeding, ascites, portal hypertension, hepatocellular carcinoma and death (3). In 2009, chronic liver disease and cirrhosis were responsible for 143,000 hospitalizations, 11,000 in-hospital deaths (7.7% death rate), and 6.7 billion dollars of hospital charges in total (4). Accurately detecting and staging fibrosis is important in the management of chronic liver disease for initiating treatment and monitoring its effects on the liver. Chronic viral hepatitis C (HCV) infection is a significant cause of hepatic disease and its treatment may depend on the presence of substantial fibrosis (5, 6). It is well known that liver biopsy is the current reference method for the detection and staging of fibrosis. However, it is an invasive method and can cause undesired complications including bleeding (1.7%) (7) and death (0.01-1%) (7-9). The accuracy of liver biopsy is affected by sampling errors (20-33% of patients can have fibrosis stage misclassified by 1 category) (10, 11), and intra- and inter-operator inconsistency (Kappa coefficient 0.62 – 0.89, where 1 means perfect agreement) (11, 12). Furthermore, this approach is not well accepted by patients and physicians alike (13). Conventional noninvasive imaging techniques (ultrasound, computed-tomography, MRI) can visualize the morphologic changes of liver due to fibrosis and cirrhosis. However, the sensitivity and accuracy of these modalities are low for detecting earlier stages of fibrosis and thus are not suitable for staging liver fibrosis over its entire spectrum (14). Over the last several years, new noninvasive methods of assessing liver fibrosis have been developed and investigated, including serum tests, diffusion-weighted MR imaging (DWI), contrast enhanced MR imaging (CE-MRI), ultrasound based transient elastography (UTE) and MR elastography (MRE). Accumulated data showed that the AUROC (area under receiver operating characteristic curve) values are between 77%-91% for serum tests (15-20), 88% for DWI (21), and 83% for CE-MRI (22) to detect the presence of liver fibrosis due to different disease causes. As one of the two existing methods of measuring liver stiffness, UTE has higher AUROC values (0.79-0.98) (23-25), yet it is less accurate for detecting early fibrosis stages and has a high technical failure rate in certain patient subsets (ascites, narrow intercostals space, obesity) (26-28). The other method of measuring liver stiffness, MR elastography (MRE) is the most accurate (AUROC = 92% - 100%) method for detecting and staging liver fibrosis to date, especially in early stages of fibrosis because of its capability of measuring cross-sectional areas of hepatic parenchyma, and the technique is not affected by the ascites and obesity (3, 21, 26, 27, 29-31). In one study, MRE even detected necroinflammation before the onset of fibrosis in patients with NAFLD (32). The detection of early stage fibrosis is of clinical significance as treatments for liver disease are thought to be more effective when compared to later stages of fibrosis. Given its technical advantages and high diagnostic accuracy, this article reviews the application of MR elastography to address clinical questions involving HCV, NAFLD, and methotrexate (MTX) exposure.

Ultrasound-based transient elastography for the detection of hepatic fibrosis in patients with recurrent hepatitis C virus after liver transplantation: A systematic review and meta-analysis

Ultrasound-based transient elastography (TE) is a promising noninvasive alternative to liver biopsy for the detection of hepatic fibrosis due to recurrent hepatitis C virus (HCV) after liver transplantation (LT). However, its overall test performance in various settings remains unknown. The aim of this study was to perform a systematic review and diagnostic accuracy meta-analysis of studies comparing ultrasound-based TE to liver biopsy for the detection of hepatic fibrosis due to a recurrent HCV infection after LT. Electronic and manual bibliographic searches (including scientific abstracts) were performed to identify potential studies. A meta-analysis was conducted to generate pooled estimates of the sensitivity values, specificity values, likelihood ratios, and diagnostic odds ratios of individual studies. The extent of the heterogeneity and the reasons for it were assessed. Six fully published studies were identified for analysis. Five studies that evaluated significant fibrosis were identified. Among these studies, the pooled estimates were 83% for sensitivity [95% confidence interval (CI) = 77%-88%], 83% for specificity (95% CI = 77%-88%), 4.95 for the positive likelihood ratio (95% CI = 3.4-7.2), 0.17 for the negative likelihood ratio (95% CI = 0.09-0.35), and 30.5 for the diagnostic odds ratio (95% CI = 12.8-72.4). For the 5 studies that assessed cirrhosis, the pooled estimates were 98% for sensitivity (95% CI = 90%-100%), 84% for specificity (95% CI = 80%-88%), 7 for the positive likelihood ratio (95% CI = 2.8-17.3), 0.06 for the negative likelihood ratio (95% CI = 0.02-0.19), and 130 for the diagnostic odds ratio (95% CI = 36.5-462.1). A diagnostic threshold (or cutoff value) bias was identified as an important cause of heterogeneity for the pooled results of both patient groups. In conclusion, ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis due to a recurrent HCV infection after LT. The detection of significant fibrosis is more accurate for these patients versus patients whose native liver is chronically infected with HCV.

Noninvasive assessment of liver fibrosis

Noninvasive assessment of liver fibrosis