Hepatic Fibrosis Stage Research Articles

MRI with diffusion-weighted image in assessment of hepatic fibrosis and steatosis

Background FibroScan and diffusion MRI have been recommended for staging and noninvasive diagnosis of hepatic fibrosis and steatosis. Aim To evaluate the diagnostic efficiency of conventional MRI and diffusion-weighted imaging in diagnosis and staging of hepatic fibrosis and steatosis. Patients and methods This research was conducted on 30 patients proven to have hepatic fibrosis or steatosis based on clinical, laboratory, and/or ultrasonographic criteria. Both sexes were included. Their age ranged from 20 to 60 years. The participants were sent to the MRI Unit in the Department of Radiodiagnosis, Tanta University Hospitals, over a period of 12 months from March 2021 till March 2022. Results There was a significant difference between apparent diffusion coefficient values of F0 and F1, F3, and F4 (P=0.010, 0.041, and 0.019, respectively); however, no significant difference was observed among the other various fibrosis stages. Conclusions FibroScan is a good noninvasive route for detection of hepatic fibrosis and steatosis. It can differentiate among various phases of hepatic fibrosis and steatosis. MRI can differentiate between fibrotic and nonfibrotic liver and also steatotic from nonsteatotic liver. However, it cannot differentiate between various phases of hepatic fibrosis and steatosis, especially the intermediate stages.

Diagnostic of FibroTouch and six serological models in assessing the degree of liver fibrosis among patients with chronic hepatic disease: A single-center retrospective study.

Background and aimsThe aim of this study was to evaluate the diagnostic value of FibroTouch and serological models on staging hepatic fibrosis in chronic liver diseases.MethodsWe recruited 850 patients undergoing liver biopsy and received FibroTouch test before or after liver biopsy within one week, blood was taken for the routine inspection before the operation within one week. The serological models were calculated by the blood results and routine clinical information. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC).ResultsPatients with severe liver fibrosis had significantly higher AST, ALT, GGT, RDW, ALP, and FT-LSM. The area under the receiver operating characteristic curve (AUROC) of FT-LSM for the liver diagnosis of S≥2, S≥3 and S = 4 was 0.75(95% confidence interval [CI]:0.72–0.78), 0.83(95% CI: 0.80–0.86), and 0.85 (95% CI: 0.81–0.89), respectively. The optimal cut-off of FT-LSM for diagnosing S≥2, S≥3 and S = 4 was 8.7, 10.7, and 12.3, respectively.ConclusionsOur study showed the FibroTouch has a higher diagnostic value compared with the non-invasive serological models in staging the fibrosis stage. The cut-off of FibroTouch and five serological models (APRI, FIB-4, S-index, Forns, and PRP) increased with the severe of fibrosis stage.

FRI092 - Diagnostic accuracy of MRE for staging hepatic fibrosis in patients with NAFLD

FRI092 - Diagnostic accuracy of MRE for staging hepatic fibrosis in patients with NAFLD

Regulation of BMP8A expression during hepatic fibrogenesis process

Introduction: Hepatocellular injury is the main triggering event of wound healing response that leads to liver fibrosis. Hepatic stellate cell (HSC) activation is crucial in the progression of fibrogenic process since they represent the major source of extracellular matrix components and contribute to the inflammatory response by secreting proinflammatory cytokines. Bone morphogenetic proteins (BMPs) are soluble growth factors which exert pleiotropic effects in various tissues regulating different physiological processes of cellular homeostasis. Regarding BMP8A, its implication in liver damage has been poorly investigated. Therefore, the aim of this study was to determine BMP8A expression in different fibrosis-mediated liver damage scenarios. Materials and methods: Histological study of livers was performed and hepatic BMP8A expression levels were determined by RT-qPCR in different experimental models of hepatic fibrosis: carbon tetrachloride injected mice, as a classic hepatic fibrosis model, mice subjected to bile duct ligation, as a model of cholestatic damage-derived hepatic fibrosis, and high fat diet fed mice, reproducing the progression of non-alcoholic fatty liver disease (NAFLD) which curses with variable states of concomitant fibrosis in advanced stages. Likewise, the same analysis was conducted in livers from 11 patients with biopsy proven NAFLD-derived fibrosis and 25 NAFLD patients without fibrosis. To reproduce the experimental conditions of the murine models, BMP8A levels were determined in hepatocytes stimulated with conditioned media derived from TGFbeta-stimulated hepatic stellate cells (LX2). Results: Firstly, murine models were validated through a histological examination of the liver and a molecular analysis of fibrotic specific markers. Next, hepatic BMP8A mRNA expression was significant increased in all studied models of hepatic fibrosis comparing with the respective controls. In fact, there is a positive correlation between hepatic BMP8A levels and fibrosis stage as well as with markers of fibrosis. Accordingly, the clinical study revealed an elevated BMP8A expression in fibrotic livers, in comparison with those without any fibrotic sign. Furthermore, in vitro experiments also showed an increased BMP8A expression in Huh7 cells treated with conditioned media derived from TGFbeta-activated LX2 cells. Conclusions: This study reveals for the first time an increased BMP8A hepatic expression in the context of hepatic fibrosis. Its detection in serum might be useful as a non-invasive tool for the diagnosis/prognosis of patients affected by this liver disease. Moreover, these results suggest that BMP8A is involved in hepatic fibrosis progression, being possibly relevant in its therapeutic manage.

Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in autoimmune hepatitis-primary biliary cholangitis overlap syndrome

BACKGROUNDAutoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome has a worse prognosis than AIH or PBC alone. Therefore, accurately staging liver fibrosis and dynamically monitoring disease progression are essential.AIMTo investigate the performance of two-dimensional shear-wave elastography (2D-SWE) for noninvasively staging liver fibrosis and assessing the clinical utility of repeated 2D-SWE for monitoring treatment response in AIH-PBC overlap syndrome.METHODSA total of 148 patients diagnosed with AIH-PBC overlap syndrome were retrospectively enrolled. Among them, 82 patients had a 2D-SWE follow-up time of more than 1 year. The Scheuer scoring system was used to evaluate stages of hepatic inflammation and liver fibrosis. The performance of 2D-SWE for staging liver fibrosis was evaluated with the liver biopsy. Changes in liver stiffness (LS) measured by 2D-SWE in patients with or without complete biochemical remission were evaluated. RESULTSLS value was strongly correlated with liver fibrosis stage (Spearman r = 0.84, P < 0.0001). The areas under the receiver operating characteristic curves of LS for diagnosing significant fibrosis (≥ S2), severe fibrosis (≥ S3), and cirrhosis (S4) were 0.91, 0.97, and 0.96, respectively. Patients with complete biochemical remission had a considerable decrease in LS values (P < 0.0001). More importantly, the declined LS in patients with S0-S2 was significantly lower than that in patients with S3-S4 (P = 0.0002). In contrast, patients who failed to achieve biochemical remission had a slight but not significant decrease in LS (P = 0.37). CONCLUSIONLS measured by 2D-SWE is an accurate and reliable method in assessing liver fibrosis, especially for diagnosing severe fibrosis (≥ 3) and monitoring treatment response in patients with AIH-PBC overlap syndrome.

Noninvasive Diagnostic Methods for the Assessment of Hepatic Fibrosis in Liver Transplant Recipients

Hepatic fibrosis in liver transplant recipients is the main predictive factor for graft function. Diagnostic methods for hepatic fibrosis staging should be available, reproducible, and noninvasive, if possible. We aimed to compare diagnostic methods for the assessment of hepatic fibrosis in transplant recipients: liver biopsy as a reference method, dynamic elastography, and direct and indirect blood markers (the ELF test [Enhanced Liver Fibrosis] test and the FibroTest). We sought to set a cutoff value for each method in order to assess significant liver fibrosis (F ≥2). The study involved 62 patients after liver transplantation. Fibrosis was assessed in biopsy specimens using the METAVIR Score System (F0-F4). To identify clinically significant cutoff values of hepatic fibrosis (F ≥2, F ≥3, F=4) for each method compared, a receiver-operating characteristic (ROC) curve analysis was used. Area under ROC for the prediction of significant fibrosis (F ≥2), advanced fibrosis (F ≥3), and cirrhosis (F=4) for the study group was 0.5938, 0.8952, and 0.9583 for dynamic elastography; 0.7295, 0.7072, and 0.8409 for the ELF test; and 0.4863, 0.8049, and 0.8723 for the FibroTest. The cutoff value for F ≥2 for dynamic elastography was 4.65 kPa; for the ELF test, 9.27; and for the FibroTest, 0.72. The sensitivity and specificity of the tests studied, as compared with biopsy results, increase with increasing severity of hepatic fibrosis. The noninvasive diagnostic methods are of limited value in the diagnosis of early fibrosis stages. In the diagnostic assessment of hepatic fibrosis in its advanced stages, dynamic elastography can be used in conjunction with ELF test as a noninvasive alternative to liver biopsy.

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

The aim of the study was to investigate the diagnostic feasibility of radiomics analysis using magnetic resonance elastography (MRE) to assess hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). One hundred patients with suspected NAFLD were retrospectively enrolled. All patients underwent a liver parenchymal biopsy. Magnetic resonance elastography was performed using a 3.0-T scanner. After multislice segmentation of MRE images, 834 radiomic features were analyzed using a commercial program. Radiologic features, such as median and mean values of the regions of interest and variable clinical features, were analyzed. A random forest regressor was used 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 was evaluated using a classifier for fibrosis stage diagnosis. 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 2 most important being wavelet-high high low gray level dependence matrix dependence nonuniformity-normalized and wavelet-high high low gray level dependence matrix dependence entropy. The median value of the multiple small regions of interest was identified as the most important radiologic feature. Platelet count has been identified as an important clinical feature. The area under the receiver operating characteristic curve of the classifier using radiomics was comparable with that of radiologic measures (0.97 ± 0.07 and 0.96 ± 0.06, respectively). Magnetic resonance elastography radiomics analysis provides diagnostic performance comparable with conventional MRE analysis for the assessment of clinically significant hepatic fibrosis in patients with NAFLD.

OPTIONS OF INTERFERON-FREE THERAPY FOR HCV INFECTION. A CASE STUDY. COMPARISON OF NON-INVASIVE METHODS FOR LIVER FIBROSIS ASSESSMENT

The incidence of hepatitis C virus infection in Russia is 2–3 %. In our country the socio-economic damage caused by the increase in the incidence of chronic hepatitis and its consequences, such as liver cirrhosis and hepatocarcinoma, is enormous. The goal of antiviral therapy for chronic hepatitis C is a sustained virological response, which is associated with a biochemical response and regression of hepatic tissue fibrosis, which leads to a decrease in the liver cirrhosis development.&#x0D; The purpose of the study is to determine the efficacy of interferon-free therapy; to compare the efficacy of non-invasive methods for liver fibrosis diagnostics in chronic hepatitis C.&#x0D; Materials and Methods. The study included 63 patients who underwent direct antiviral therapy (dasabuvir and ombitasvir + paritaprevir + ritonavir (3D-therapy)) in combination with ribavirin or without it, depending on the hepatitis C virus genotype and the stage of liver fibrosis. The stage of hepatic tissue fibrosis was assessed by non-invasive methods, namely, elastography and vibration-controlled transient elastometry using FibriScanCompact 530 (Echosens, France). Liver fibrosis biomarkers (AAR, APRI, Fib-4, Forns index) were calculated; MDA test was conducted.&#x0D; Results. 100 % efficacy of dasabuvir and ombitasvir + paritaprevir + ritonavir was confirmed for both 8- and 12-week therapy in comorbid patients with extrahepatic manifestations, patients who underwent interferon-based therapy, regardless of liver fibrosis stage and disease duration.&#x0D; The article provides a comparative description of non-invasive methods for assessing liver fibrosis in patients with chronic hepatitis C: elastography, elastometry and serum fibrosis indices (APRI, AAR, FIB-4, MDA, Forns index). Indirect fibrosis markers are useful, because they allow to determine the late stages of liver fibrosis (F3-F4 on the METAVIR scale) with a very high degree of confidence.

Evaluating Serum Neuregulin 4 as a Noninvasive Biomarker in Patients with Non-alcoholic Fatty Liver Disease

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) spectrum ranges from simple hepatic steatosis to non-alcoholic steatohepatitis. Considering the restrictions of liver biopsy, various serological biomarkers have recently emerged for non-invasive diagnosis of NAFLD. AIM: This study aimed to evaluate the association between serum neuregulin 4 (Nrg4) and NAFLD and the use of serum Nrg4 as a noninvasive marker for diagnosis of NAFLD. METHODS: Sixty-three Egyptian NAFLD patients and 63 controls were enrolled and subjected to detailed history taking, thorough clinical examination including anthropometric measures (body mass index [BMI] and waist circumference). Laboratory investigations included complete blood count, lipid profile (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triglycerides), serum albumin, transaminases, bilirubin levels, hepatitis markers (anti-HCV antibodies and hepatitis B surface antigen), anti-nuclear antibodies and anti-smooth muscle antibody. Measurement of serum Nrg4 by ELISA and non-invasive NAFLD scores such as NAFLD fibrosis score and FIB4 score were applied to all patients. RESULTS: There was a statistically significant difference between cases and controls regarding the BMI, waist circumference, hemoglobin level, total leukocytic count, total cholesterol, LDL-C, HDL-C, and serum triglycerides levels. Nrg4 was significantly decreased in NAFLD patients as compared to controls. Moreover, Nrg4, total cholesterol, and LDL-C levels were statistically significant independent predictors of NAFLD. No significant differences were observed between Nrg4 level and the variable stages of hepatic fibrosis by NAFLD fibrosis score. CONCLUSION: Decreased serum Nrg4 level is frequent in NAFLD patients and is an independent predictor of NAFLD, suggesting that Nrg4 might have a potential role in prevention and treatment of NAFLD.

The Role and Significance of Non-invasive Methods, with a Particular Focus on Shear Wave Elastography in Hepatic Fibrosis Staging

Shear Wave Elastography (SWE) represents a new, non-invasive method, used in the diagnosis of diffuse liver diseases. The method has been widely used instead of liver biopsy - an invasive procedure with potential major risk complications. Compared to liver biopsy, SWE provides an examination of larger areas of the liver, thus providing better staging of hepatic fibrosis. &#x0D; 30 patients were included in the study on basis of previous clinical, biochemical, and ultrasound findings indicating a presence of a chronic liver lesion. Patients were divided into three groups: 6 patients with steatosis, 13 patients with viral hepatitis, and 11 patients with liver cirrhosis. Liver damage biochemical markers, serum markers of liver fibrosis, and SWE were determined in all patients. Statistical analysis revealed a positive correlation between SWE results, and the values of biochemical markers of the hepatic lesion, as well as serum markers of liver fibrosis.

The Glycodiversity of HCV E2 Glycoprotein-Specific Antibodies as a Signature of Hepatic Damage and Virotherapy Efficacy

The HCV E2 glycoprotein-specific Abs (E2-Ab) is an important factor in the host resistance to hepatitis C virus (HCV) infection. There is evidence that the E2-Ab sialylation is associated with liver damage and virotherapy efficacy. The aim of this study was to further profile the E2-Ab glycosylation. The fucosylation and sialylation of E2-Ab in one hundred six (HCV)-infected patients were tested using the lectin-based ELISA platform. Data were analyzed by the stage of hepatic fibrosis, HCV genotype and the response to IF-RBV virotherapy. The changes in the E2–Ab glycosylation were also evaluated by the receiver operator characteristic curve (ROC) and multiple regression analysis. The E2-Ab reactivity to fucose-specific Aleuria aurantia lectin (AAL) and sialo-specific Sambucus nigra agglutinin (SNA) was decreased in the advanced stages of liver fibrosis. The SNA binding analysis was more informative in the discrimination of patients with advanced fibrosis compared to those with earlier fibrosis stages or no fibrosis group. No significant correlation between the reactivities of SNA and AAL lectins was established irrespective of HCV genotype. The patients infected with HCV 3a genotype showed an increased E2-Ab fucosylation, a lower E2-SNA/E2-AAL ratio and a better response to virotherapy. The association of the E2-SNA/E2-AAL ratio with virotherapy outcome was observed in patients infected with HCV 1b genotype. A better response to IF-RBV therapy was found in patients with a higher fucosylated E2 Abs and a lower E2-SNA/E2-AAL ratio. Thus the significance of E2 antibodies in the course of HCV hepatitis was demonstrated to be dependent on their glycosylation, the sialylation/fucosylation ratio, as well as on HCV genotype.

Usefulness of 2D shear wave elastography for the evaluation of hepatic fibrosis and treatment response in patients with autoimmune hepatitis.

PurposeThe purpose of this study was to determine the usefulness of two-dimensional shear wave elastography (2D SWE) in the assessment of liver stiffness (LS) and dispersion slope (DS) to evaluate hepatic fibrosis and the treatment response in patients with autoimmune hepatitis (AIH).MethodsPatients diagnosed with AIH who underwent 2D SWE between June 2014 and June 2021 were enrolled in this retrospective study. The patients were classified into four groups according to the histologic stage of fibrosis (F1-F4). The baseline characteristics, laboratory test results, histologic results, and 2D SWE results were analyzed. The diagnostic performance of LS measurements in hepatic fibrosis staging was investigated, and variables were compared before and after steroid treatment for AIH.ResultsIn total, 69 patients were analyzed. The LS values differed according to the stage of liver fibrosis (P<0.001). The area under the curve for LS was 0.903, 0.815, and 0.854 for ≥F2, ≥F3, and F4, respectively. The diagnostic performance of LS measurements was significantly greater than that of serum biomarkers, except for fibrosis index-4 for F4 (P<0.05). Significant differences were observed in follow-up examinations in both the LS value and DS in patients who received steroid therapy (P=0.012 and P=0.011, respectively).ConclusionIn conclusion, 2D SWE is a useful method for the assessment of hepatic fibrosis in patients with AIH. In follow-up examinations, LS and DS can be used as reliable parameters to evaluate the treatment response of AIH.

Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease: A long-term follow-up study.

Background and AimsThe presence of advanced hepatic fibrosis is the prime marker for the prediction of liver‐related complications in non‐alcoholic fatty liver disease (NAFLD). Blood‐based non‐invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2–3‐year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.MethodsWe retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow‐up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end‐stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow‐up: Fibrosis‐4 (FIB‐4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate‐to‐alanine aminotransferase ratio (dAAR).ResultsOne hundred and thirty‐five patients were included with a mean follow‐up of 12.6 ± 8.5 years. During follow‐up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow‐up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56–0.64 and positive predictive values of 0.28–0.36 at sensitivity fixed at 90%.ConclusionsChange of FIB‐4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.

Endoscopic Ultrasound-Guided Porto-systemic Pressure Gradient Measurement Correlates with Histological Hepatic Fibrosis.

Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.

2-Step PLT16-AST44 method: Simplified liver fibrosis detection system in patients with non-alcoholic fatty liver disease.

Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non-alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early-stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. We developed a novel simplified ≥F1 detecting system, designated as 2-Step PLT16-AST44 method, where (1) PLT of 16×104 /μl or less, or (2) PLT greater than 16×104 /μl and AST greater than 44U/L is determined as having ≥F1 fibrosis. The 2-Step PLT16-AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2-Step PLT16-AST44 method's power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB-4, and APRI. We propose the 2-Step PLT16-AST44 method as a simple and beneficial early-stage hepatic fibrosis detection system.

Diagnostic performance of liver fibrosis assessment by quantification of liver surface nodularity on computed tomography and magnetic resonance imaging: systematic review and meta-analysis.

To determine the diagnostic performance of the liver surface nodularity (LSN) score for assessment of hepatic fibrosis. Major databases were searched to identify studies reporting the diagnostic performance of the LSN score published from January 2011 to April 2021. The pooled sensitivity and specificity of the LSN score in the diagnosis of significant fibrosis (F2-4), advanced fibrosis (F3-4), and liver cirrhosis (F4) were calculated using a bivariate random-effects model, and the summary areas under the hierarchical summary receiver operating characteristics curve (AUC) for each were calculated. Subgroup analysis was performed to explore the causes of study heterogeneity. Of 168 screened studies, six were included in the analysis. The pooled sensitivity, specificity, and AUC of the LSN score were 68% (95% confidence interval [CI], 45-84%), 89% (95% CI, 83-93%), and 0.90 (95% CI, 0.87-0.92), respectively, for the diagnosis of significant fibrosis; 88% (95% CI, 60-97%), 78% (95% CI, 57-90%), and 0.89 (95% CI, 0.86-0.91), respectively, for the diagnosis of advanced fibrosis; and 83% (95% CI, 71-91%), 80% (95% CI, 72-85%), and 0.87 (95% CI, 0.83-0.89), respectively, for the diagnosis of liver cirrhosis. Cutoff values of the LSN score affected study heterogeneity in the diagnosis of advanced fibrosis (p = 0.03) and liver cirrhosis (p = 0.01). Imaging modality (p = 0.01) and reference standard (p = 0.01) affected study heterogeneity in the diagnosis of liver cirrhosis. The LSN score showed good diagnostic performance in assessing the hepatic fibrosis stage. Additional investigations are needed to improve and standardize the LSN score. Key Points • The liver surface nodularity (LSN) score showed overall good diagnostic performance in assessing hepatic fibrosis. • The pooled sensitivity of the LSN score was highest in the diagnosis of advanced fibrosis (88%; 95% confidence interval [CI], 60-97%), and the pooled specificity was highest in the diagnosis of significant fibrosis (89%; 95% CI, 83-93%). • The diagnostic performance of the LSN score differed according to the cutoff value, imaging modality, and reference standard.

Diagnostic performance of 2D-shear wave elastography and serum fibrosis markers for evaluation of hepatic graft fibrosis in pediatric liver-inclusive transplant recipients: A prospective pilot study.

Liver biopsy is the gold standard for hepatic fibrosis staging, but it is invasive and has potential severe complications. We aimed to determine the diagnostic performance of 2D-SWE and serum markers to predict significant hepatic graft fibrosis (≥F2) in pediatric liver-inclusive transplant recipients. This prospective, cross-sectional pilot study included children younger than 19years who had received a LT or LSBT and underwent a liver biopsy performed for clinical indications. LS was measured using 2D-SWE. The AUROC was calculated to evaluate the diagnostic performance of 2D-SWE and biomarkers (AST/ALT ratio, APRI, FIB4) for predicting significant fibrosis. Twenty-two children (13males, 8 LSBT) were included. Eighteen (81.8%) children received a whole liver graft. Thirteen (59.1%) patients had hepatic fibrosis (≥F1) and four (18.2%) had significant fibrosis. The AUROCs of AST/ALT ratio, APRI, and FIB4 for predicting significant hepatic graft fibrosis were 0.71 (p=.29), 0.85 (p=.0001), and 0.76 (p=.03), respectively. When FIB4 was calculated using the hepatic graft's age, its AUROC improved to 0.85 (p<.0001). The AUROC of 2D-SWE for predicting significant hepatic graft fibrosis was 0.80 (p=.046). When 2D-SWE was combined with APRI or FIB4, its AUROC improved to 0.82 (p=.08) and 0.87 (p=.002), respectively. APRI and FIB4 can accurately predict significant hepatic graft fibrosis. 2D-SWE may serve as a valuable adjunct tool to detect significant graft fibrosis, especially when combined with these serum markers.

Diagnostic value of transient elastography in the staging of hepatic fibrosis in patients with autoimmune liver disease: A Meta-analysis

Diagnostic value of transient elastography in the staging of hepatic fibrosis in patients with autoimmune liver disease: A Meta-analysis

Investigating the association of toll-like receptor 9 rs5743836, rs352140, and rs187084 gene polymorphisms and their mRNA levels with different hepatic fibrosis stages of non-alcoholic fatty liver patients compared to healthy controls.

Recent studies have shown that the level of hepatocyte-derived mitochondrial DNA is elevated in plasma samples obtained from mice and NASH patients, and it has the ability to toll-like receptor 9 (TLR9) activation resulting in steatosis, hepatocyte injury, and fibrosis. In this study, we explored the association between TLR9 rs5743836, rs352140, and rs187084 polymorphism and its plasma mRNA level in non-alcoholic fatty liver (NAFL) patients with different liver fibrosis scores compared to healthy controls. Seventy Iranian patients diagnosed with NAFL, based on fibroscan testing results, were divided into F0-F1 (N=33), F2-F3 (N=19), and F4 (N=18) hepatic fibrosis groups and compared to 22 healthy controls. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the mRNA expression level of TLR9 was determined using Real-Time PCR analysis. Results showed no significant association between allelic and genotypic distribution frequency of TLR9 rs5743836, rs352140, and rs187084 polymorphisms in NAFL patients with hepatic fibrosis compared to healthy controls (P>0.05). However, the mRNA level of TLR9 was significantly elevated in correlation with hepatic fibrosis progression in NAFL patients compared to healthy controls (P<0.05). As a preliminary study, our data showed a correlative overexpression of TLR9 mRNA with hepatic fibrosis progression in NAFL patients without the effectiveness of TLR9 gene polymorphisms.

Diagnostic Performance of Spin-Echo Echo-Planar Imaging Magnetic Resonance Elastography in 3T System for Noninvasive Assessment of Hepatic Fibrosis.

ObjectiveTo validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard.Materials and MethodsThis retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0–F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal–Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis.ResultsInter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97–0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0–F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97–0.98 (sensitivity 91.2%–95.9%, specificity 90.7%–99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0–F3 stages.ConclusionThe 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.