Comparative diagnostic performance of ultrasound shear wave elastography and magnetic resonance elastography for classifying fibrosis stage in adults with biopsy-proven nonalcoholic fatty liver disease

Objectives To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). Methods Patients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE. Results In total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m2) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54–0.76) and 0.81 (0.72–0.89), 0.81 (0.71–0.91) and 0.94 (0.89–1.00), 0.85 (0.74–0.96) and 0.95 (0.89–1.00), and 0.91 (0.79–1.00) and 0.92 (0.83–1.00), for detecting fibrosis stage ≥ 1, ≥ 2, ≥ 3, and = 4, respectively. The differences were significant for detecting fibrosis stage ≥ 1 and ≥ 2 (p < 0.01) but not otherwise. At ≥ 90% sensitivity cutoff, MRE yielded higher specificity than SWE at diagnosing fibrosis stage ≥ 1, ≥ 2, and ≥ 3. At ≥ 90% specificity cutoff, MRE yielded higher sensitivity than SWE at diagnosing fibrosis stage ≥ 1 and ≥ 2. Conclusions In adults with NAFLD, MRE was more accurate than SWE in diagnosing stage ≥ 1 and ≥ 2 fibrosis, but not stage ≥ 3 or 4 fibrosis. Key Points • For detecting any fibrosis or mild fibrosis, MR elastography was significantly more accurate than shear wave elastography. • For detecting advanced fibrosis and cirrhosis, MRE and SWE did not differ significantly in accuracy. • For excluding advanced fibrosis and potentially ruling out the need for biopsy, SWE and MRE did not differ significantly in negative predictive value. • Neither SWE nor MRE had sufficiently high positive predictive value to rule in advanced fibrosis.

Dynamics of Circulating miR-122 Predict Liver Cancer and Mortality in Japanese Patients with Histopathologically Confirmed NAFLD and Severe Fibrosis Stage

<b><i>Introduction:</i></b> It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). <b><i>Methods:</i></b> This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. <b><i>Results:</i></b> The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios &#x3c;0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios &#x3c;0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates. <b><i>Conclusions:</i></b> Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.

Assessment of liver fibrosis in children with chronic HBV infection by non!invasive methods

Purpose — to assess liver fibrosis in children with chronic HBV infection with nonEinvasive methods: instrumental (shear wave elastography) and serological (APRI score). Materials and methods. 70 children with HCV aged 2–17 years were examined. The stage of liver fibrosis was determined by the APRI index and the method of shear wave elastography. Results. The majority (82.8%; n=58) of children were diagnosed with HBeAgEpositive HBV infection: HBeAg-positive chronic hepatitis occurred in 54.3% (n=38) of children, HBeAg-positive chronic infection in 28.6% (n=20). 15.7% (n=11) of children had HBeAg-negative chronic infection, and only one (1.4%) patient had HBeAg-negative chronic hepatitis. According to the results of shear wave elastography, in 64.3% (n=45) the stage of liver fibrosis F0-1 was diagnosed; in 35.7% (n=25) — stage of fibrosis >F2. According to APRI score, 63.0% (n=44) had liver fibrosis F0-1, and liver fibrosis stage >F2 was diagnosed in 37.2% (n=26). According to liver elastography, 42.0% of patients with HBeAg-positive chronic hepatitis were diagnosed with liver fibrosis stage >F2. According to APRI score, almost 66% (n=46) of children with HBeAg-positive chronic hepatitis had progressive liver fibrosis >F2. According to the correlation analysis results, a direct correlation was found between liver enzymes levels and APRI score — ALT (τ=0.67; p<0.05), AST (τ=0.72; p<0.05) and GGT (τ=0.26; p<0.05). Conclusions. Most children with chronic HBV infection had stage F0-1 liver fibrosis according to both elastography and APRI score (64% and 63%, respectively). Elastography fibrosis stage >F2 was diagnosed in 42% of HBeAg-positive chronic hepatitis, while APRI index fibrosis stage >F2 was diagnosed in 66% of patients with HBeAg-positive chronic hepatitis. Thus, the results of the liver fibrosis evaluation according to the liver elastography and APRI score in children with chronic HBV infection are similar and can be used in clinical practice to select patients who require antiviral therapy. The APRI score depends on the activity of hepatitis and its use in children with HBeAg-positive chronic hepatitis has certain limitations. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, chronic HBV infection, fibrosis, shear wave elastography, APRI.

Liver biopsy complication rates in patients with non-alcoholic fatty liver disease

BACKGROUND: With new treatments for non-alcoholic fatty liver disease (NAFLD) on the horizon, it will be important to risk-stratify patients based on degree of fibrosis to allocate treatment to those at highest risk. No studies have examined the complication rates of liver biopsies in patients with NAFLD in the outpatient setting. METHODS: We conducted a retrospective chart review of all outpatient elective liver biopsies for NAFLD at a tertiary care centre over a 10-year period. Demographic variables and stage of fibrosis were recorded. Complications up to 1-week post-procedure were recorded. We used univariate logistic regression models to estimate the odds of major complications by fibrosis stage, age, sex, platelets, and international normalized ratio (INR). RESULTS: There were 582 biopsies reviewed in total. The mean age was 53 years. There was an even proportion of males to females. The mean fibrosis stage was 1.9; platelet count was 223.9, INR was 1, and partial thromboplastin time (PTT) was 31. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. There were no statistically significant associations between age (odds ratio [OR] 0.97, 95% CI 0.92–1.03), female sex (OR 1.00, 95% CI 0.25–4.04), platelet count <150 (OR 0.59, 95% CI [-inf.], 3.86), INR >1.3 (OR 0.47, 95% CI 0.057–3.85), fibrosis stage, and complication rate. CONCLUSIONS: Our results are consistent with previous studies examining complication rates in other patient populations and clinical settings and support the overall safety of liver biopsies.

Evaluation of Rabbits Liver Fibrosis Using Gd-DTPA-BMA of Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Objective. To evaluate the different pharmacokinetic parameters of the DCE-MRI method on diagnosing and staging of rabbits’ liver fibrosis. Methods. We had performed DCE-MRI for rabbits that had been divided into the experiment group and the control group. Then, rabbits’ images were transferred to a work station to get three parameters such as Ktrans, Kep, and Ve, which had been measured to calculate. After data were analyzed, ROC analyses were performed to assess the diagnostic performance of Ktrans, Kep, and Ve to judge liver fibrosis. Results. The distribution of the different liver fibrosis group was as follows: F1, n = 8; F2, n = 9; F3, n = 6; F4, n = 5. No fibrosis was deemed as F0, n = 6. Kep is statistically significant P < 0.05 for F0 and mild liver fibrosis stage, and the Kep shows AUC of 0.814. Three parameters are statistically significant for F0 and advanced liver fibrosis stage (Ktrans and Kep, P < 0.01 ; Ve, P < 0.05 ), and the Ktrans shows AUC of 0.924; the Kep shows AUC of 0.909; the Ve shows AUC of 0.848; Ktrans and Kep are statistically significant for mild and advanced liver fibrosis stages (Ktrans, P < 0.01 ; Kep, P < 0.05 ), and the Ktrans shows AUC of 0.840; the Kep shows AUC of 0.765. Both Ktrans and Kep are negatively correlated with the liver fibrosis stage. Ve is positively correlated with the liver fibrosis stage. Conclusion. Ktrans is shown to be the best DCE parameter to distinguish the fibrotic liver from the normal liver and mild and advanced fibrosis. On the contrary, Kep is moderate and Ve is worst. And Kep is a good DCE parameter to differentiate mild fibrosis from the normal liver.

Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. In adults with NAFLD, fibrosis can develop and progress to liver cirrhosis and liver failure. However, the underlying molecular mechanisms of fibrosis progression are not fully understood. Using total RNA-Seq, we investigated the molecular mechanisms of NAFLD and fibrosis. We sequenced liver tissue from 143 adults across the full spectrum of fibrosis stage including those with stage 4 fibrosis (cirrhosis). We identified gene expression clusters that strongly correlate with fibrosis stage including four genes that have been found consistently across previously published transcriptomic studies on NASH i.e. COL1A2, EFEMP2, FBLN5 and THBS2. Using cell type deconvolution, we estimated the loss of hepatocytes versus gain of hepatic stellate cells, macrophages and cholangiocytes with advancing fibrosis stage. Hepatocyte-specific functional analysis indicated increase of pro-apoptotic pathways and markers of bipotent hepatocyte/cholangiocyte precursors. Regression modelling was used to derive predictors of fibrosis stage. This study elucidated molecular and cell composition changes associated with increasing fibrosis stage in NAFLD and defined informative gene signatures for the disease.

Diagnostic Value of Magnetic Resonance Elastography Radiomics Analysis for the Assessment of Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Background: To investigate the diagnostic performance of radiomics analysis using magnetic resonance elastography (MRE) toward assessing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 100 patients with suspected NAFLD were retrospectively enrolled. All patients underwent a liver parenchymal biopsy. MRE was performed using a 3.0-T scanner. Following three-dimensional (3D) segmentation of MRE images, 834 radiomic features were analyzed using a commercial program. Radiologic features, such as median and mean values of two-dimensional (2D) or 3D regions of interest (ROIs) and variable clinical features, were analyzed. A random forest regressor was employed to extract important radiomic, radiological, and clinical features. A random forest classifier model was trained to use these features to classify the fibrosis stage. The area under the receiver operating characteristic curve (AUC) was evaluated using a classifier for fibrosis stage diagnosis. Results: The pathological hepatic fibrosis stage was classified as low-grade fibrosis (stages F0–F1, n = 82) or clinically significant fibrosis (stages F2–F4, n = 18). Eight important features were extracted from radiomics analysis, with the two most important being wavelet-HHL gray level dependence matrix (GLDM)-dependence non-uniformity-normalized and wavelet-HHL GLDM-dependence entropy. The median value of the 2D ROI was identified as the most important radiologic feature. Platelet count was identified as an important clinical feature. The AUC of the classifier using radiomics was comparable to that of radiologic measures (0.97 ± 0.07 vs. 0.96 ± 0.06). Conclusions: MRE radiomics analysis provides diagnostic performance comparable to conventional MRE analysis for the assessment of clinically significant hepatic fibrosis in patients with NAFLD.