Staging Liver Fibrosis In Patients Research Articles

Staging liver fibrosis: comparison of radiomics model and fusion model based on multiparametric MRI in patients with chronic liver disease.

To develop and compare radiomics model and fusion model based on multiple MR parameters for staging liver fibrosis in patients with chronic liver disease. Patients with chronic liver disease who underwent multiparametric abdominal MRI were included in this retrospective study. Multiparametric MR images were imported into 3D-Slicer software for drawing bounding boxes on MR images. By using a 3D-Slicer extension of SlicerRadiomics, radiomics features were extracted from these MR images. The z-score normalization method was used for post-processing radiomics features. The least absolute shrinkage and selection operator method (LASSO) was performed for selecting significant radiomics features. The logistic regression analysis was used for building the radiomics model. A fusion model was built by integrating serum fibrosis biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4) with radiomics signatures. In the training cohort, AUCs of radiomics and fusion model were 0.707-0.842 and 0.718-0.854 for differentiating different groups. In the testing cohort, AUCs were 0.514-0.724 and 0.609-0.728. For the training cohort, there was no significantdifference of AUCs between radiomics and fusion model (p > 0.05). For the testing cohort, AUCs of fusion model were higher than those of radiomics model in differentiating F1-3 vs. F4 and F1-2 vs. F4 (p = 0.011 & 0.042). Radiomics model and fusion model based on multiparametric MRI exhibited the feasibility for staging liver fibrosis in patients with CLD, and APRI and FIB-4 could improve the diagnostic performance of radiomics model in differentiatingF1-3 vs. F4 and F1-2 vs. F4.

Serum level of full-length connective tissue growth factor reflects liver fibrosis stage in patients with Fontan-associated liver disease.

Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.

MR Elastography: Practical Questions, From the AJR Special Series on Imaging of Fibrosis.

MR elastography (MRE), first described in 1995 and FDA-cleared in 2009, has emerged as an important tool for noninvasively detecting and staging liver fibrosis in patients with known or suspected chronic liver disease. This review focuses on a series of practical questions about the clinical use of MRE. Most head-to-head comparison studies with other laboratory and imaging-based tests have concluded that MRE has the highest diagnostic performance among tests for staging liver fibrosis. Limitations in the accuracy of biopsy as a standard of truth in staging liver fibrosis are increasingly being recognized. MRE-based measurements show promise as quantitative surrogates of disease severity and predictors of important clinical outcomes. The appropriate role of MRE in the management of patients with chronic liver disease is being actively incorporated into recognized clinical guidelines. Growing evidence shows that MRI measurement of elevated liver fat is the most important single biomarker for detecting nonalcoholic steatohepatitis (NASH) and that MRE-based liver stiffness is the most important single biomarker for detecting at-risk NASH (i.e., NASH with stage ≥ F2 fibrosis). Advances in MRE technology are offering higher precision and new biomarkers, which have potential to allow independent assessment of inflammation and other histologic processes in addition to fibrosis.

RDW-SD is Superior to RDW-CV in Reflecting Liver Fibrosis Stage in Patients with Chronic Hepatitis B.

The clinical significance of the red blood cell distribution width (RDW)-coefficient of variation (RDW-CV) has been recognized in numerous diseases, but few studies have investigated the usefulness of RDW-standard deviation (RDW-SD). This study aimed to compare the utility of RDW-SD and RDW-CV in evaluating liver fibrosis stage in patients with chronic hepatitis B (CHB). In this retrospective study, we enrolled 720 treatment-naïve CHB patients and 578 healthy controls, and evaluated their clinical parameters. In CHB patients, the associations between RDW-CV and liver fibrosis stage were analyzed as compared to RDW-SD using one-way analysis of variance (ANOVA), Spearman's rank correlation, student's t-test, binary logistic regression, and receiver operating characteristic (ROC) curve. RDW-SD, rather than RDW-CV was significantly elevated in CHB patients compared with healthy controls. Correlation analysis showed a stronger association between RDW-SD and liver fibrosis stage than RDW-CV in CHB patients. RDW-CV and RDW-SD are both independent predictors of significant fibrosis. For the diagnosis of significant fibrosis, the area under the receiver operating characteristic curve (AUC) for RDW-CV was 0.599, while for RDW-SD, it was 0.706. RDW-to-platelet ratio (RPR), a novel index for liver fibrosis calculated as RDW-CV/platelet, exhibited an AUC of 0.730. This AUC increased to 0.752 when RDW-CV in the RPR formula was replaced with RDW-SD. Additionally, subgroup analyses based on age, gender, and HBeAg status showed that the AUC for RDW-SD in diagnosing significant fibrosis was significantly greater than that for RDW-CV, with statistically significant differences. RDW-SD showed superiority in reflecting liver fibrosis stage and diagnosing liver significant fibrosis than RDW-CV in treatment-naïve CHB patients.

Evaluation of blood-based PRO-C3 testing as a diagnostic marker for staging liver fibrosis: A systematic review and meta-analysis.

With the global increase in chronic liver disease and cirrhosis, there is an increasing need to identify non-invasive biomarkers to measure the severity of disease progression while reducing reliance on pathological biopsies. This study aimed to comprehensively evaluate the diagnostic value of PRO-C3 as a biomarker for staging liver fibrosis in patients with viral hepatitis or fatty liver disease. Articles published until January 6, 2023, were searched in the PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate the quality of the included studies. Pooled sensitivity, specificity, diagnostic odds ratio, and likelihood ratios were integrated using a random-effects model, and a summary receiver operating characteristic curve was constructed. Publication bias was also detected. Subgroup and meta-regression analyses, as well as sensitivity analysis, were also performed. Fourteen studies with 4315 patients were included. Summary area under the curve of PRO-C3 for the identification of significant fibrosis (≥F2) and advanced fibrosis (≥F3) was 0.80 (95% confidence interval: 0.76-0.83). Subgroup and meta-regression analyses suggested that disease type and sample size may be the primary factors of heterogeneity in PRO-C3 diagnosis of ≥F2, while study design, study sample type, and enzyme-linked immunosorbent assay kit brand may be the primary sources of heterogeneity in PRO-C3 diagnosis of ≥F3. PRO-C3 demonstrated clinically meaningful diagnostic accuracy when used alone as a non-invasive biomarker for diagnosing the liver fibrosis stage in individuals with viral hepatitis or fatty liver disease.

Correlation between a New Point-Shear Wave Elastography Device (X+pSWE) with Liver Histology and 2D-SWE (SSI) for Liver Stiffness Quantification in Chronic Liver Disease.

The aim of this study was to investigate the feasibility, the correlation with previously validated 2D-SWE by supersonic imagine (SSI), and the accuracy in fibrosis-staging of a novel point shear-wave elastography device (X+pSWE) in patients with chronic liver disease. This prospective study included 253 patients with chronic liver diseases, without comorbidities potentially affecting liver stiffness. All patients underwent X+pSWE and 2D-SWE with SSI. Among them 122 patients also underwent liver biopsy and were classified according to histologic fibrosis. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while receiver operator characteristic curve (ROC) analysis with Youden index was used to establish thresholds for fibrosis staging. A very good correlation was found between X+pSWE and 2D-SWE with SSI (r2 = 0.94; p < 0.001), with X+pSWE average liver stiffness values 0.24 kPa lower than those obtained with SSI. AUROC of X+pSWE for the staging of significant fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4) using SSI as a reference standard was 0.96 (95% CI, 0.93-0.99), 0.98 (95% CI, 0.97-1) and 0.99 (95% CI, 0.98-1), respectively. The best cut-off values for diagnosing fibrosis ≥F2, ≥F3 and F4 were, respectively, 6.9, 8.5 and 12 for X+pSWE. According to histologic classification, X+pSWE correctly identified 93 out of 113 patients (82%) for F ≥ 2 and 101 out of 113 patients (89%) for F ≥ 3 using the aforementioned cut-off values. X+pSWE is a useful novel non-invasive technique for staging liver fibrosis in patients with chronic liver disease.

Staging liver fibrosis in patients with chronic hepatitis B using two-dimensional shear wave elastography based on histopathological findings: a prospective multicenter study.

With the rapid development of shear wave elastography technology, the clinical application prospect of two-dimensional shear wave elastography (2D SWE) for non-invasive monitoring of liver fibrosis is extremely promising. This study aimed to evaluate the diagnostic performance of ElastQ, a noval 2D SWE method, in the staging of liver fibrosis in patients with chronic hepatitis B with histopathological results as the reference standard. Between August 2020 and December 2021, a prospective multicenter study of 602 consecutive patients with chronic hepatitis B was conducted in 14 hospitals. All patients underwent liver biopsy and 2D SWE examination. The patients were divided into a training cohort and a validation cohort. The area under the receiver operating characteristic curve (AUROC) was calculated, and the optimal cut-off values for ElastQ were obtained. Overall, 2D SWE values showed a strong correlation with fibrosis stage (r=0.71, P<0.001). In the training cohort, the AUROCs of ElastQ for diagnosing fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 0.817 [95% confidence interval (CI): 0.777-0.853), 0.887 (95% CI: 0.852-0.915), 0.912 (95% CI: 0.881-0.937), and 0.832 (95% CI: 0.793-0.866)], respectively. In the validation cohort, the AUROCs of ElastQ for diagnosing fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 0.807 (95% CI: 0.742-0.861), 0.868 (95% CI: 0.810-0.914), 0.855 (95% CI: 0.796-0.903), and 0.851 (95% CI: 0.791-0.900), respectively. The optimal liver stiffness cut-off values for the identification of fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 5.72 kPa (sensitivity: 78%, specificity: 70%), 6.85 kPa (sensitivity: 77%, specificity: 86%), 7.43 kPa (sensitivity: 80%, specificity: 86%), and 8.03 kPa (sensitivity: 81%, specificity: 73%), respectively. Two-dimensional SWE can accurately stage liver fibrosis in patients with chronic hepatitis B.

Noninvasive diagnosis of liver fibrosis in schistosomiasis japonica: Opportunities and challenges

Schistosomiasis is an infectious disease caused by trematode parasites of the genus Schistosoma. According to the World Health Organization (WHO), it is estimated that about 250 million people in the world are infected with the disease, nearly 800 million people are at risk of infection, and more than 200,000 people die of schistosomiasis every year.1, 2 In China, the endemic species of schistosome that primarily infects humans is Schistosoma japonicum. Schistosomiasis japonica has been a major public health problem affecting human health and economic development in the past decades. The latest national epidemiological data showed that there were still 29,517 advanced cases of schistosomiasis japonica at the end of 2020. Moreover, approximately 842,500 patients had been previously infected with S. japonicum nationwide, of whom 83.3% had chronic schistosomiasis.3 Our previous studies confirmed that past cases have no possibility of re-infection after antiparasitic treatment and that liver fibrosis continues to progress and eventually develops into advanced schistosomiasis.4 Some studies have also shown that although chemotherapy with praziquantel is readily available and has good efficacy, liver fibrosis remains the most serious consequence of S. japonicum chronic infection, with an incidence of nearly 20% in infected patients.5 Hence, nearly one million patients with chronic schistosomiasis are at risk of later developing liver fibrosis. Unlike Schistosoma haematobium which causes urinary tract morbidities, S. japonicum causes gastrointestinal and liver diseases. In the human host, some schistosome eggs excreted by adult parasites that have settled in the mesenteric venous plexuses are transported by mesenteric circulation to the liver, where they are trapped in small portal branches. A granulomatous cell-mediated response to egg antigens occurs around the eggs, resulting in the excessive production and deposition of collagen along the portal vein and tract branches by activated hepatic stellate cells. Repeated embolization of eggs over time, especially in cases of high-burden infection, leads to hepatosplenic schistosomiasis (HSS) or also known as Symmers' fibrosis, a form of hepatopathy that results in periportal fibrosis (PPF) with portal hypertension. HSS represents one of the most common chronic sequelae of this infection.6, 7 Patients with periportal fibrosis retain hepatocellular function, differentiating the disease from cirrhosis and other liver diseases (Table 1).8 Confluent granulomata around trapped helminth ova → portal “pipe-stem” fibrosis around portal vessels; liver parenchyma preserved Liver cell necrosis followed by nodular hepatocellular regeneration and fibrous septa and bands involving the entire liver parenchyma Presinusoidal block; normal occluded hepatic venous pressure Sinusoidal block; increased occluded hepatic venous pressure Liver function preserved Liver function impaired Normal hepatic vein pressure gradient Increased hepatic vein pressure gradient The presence and severity of liver fibrosis determines the prognosis and clinical management. Therefore, the early diagnosis and long-term dynamic monitoring of liver fibrosis are clinically important. According to the consensus on the diagnosis and therapy of liver fibrosis (2019) issued by the Chinese Medical Association, liver biopsy remains the gold standard for the diagnosis of liver fibrosis. The hepatic venous pressure gradient (HVPG) is significantly related to the stage of liver fibrosis and is the gold standard for the diagnosis and risk classification of portal hypertension. Liver biopsy is an invasive examination that causes discomfort to patients. Additionally, cases may result in complications, such as bleeding and sepsis, that are not easily accepted by patients. Moreover, the uneven distribution of fibrosis in the liver often leads to sampling errors, resulting in the underestimation of stages of fibrosis and missed diagnosis of liver cirrhosis. The histological analysis relies on the experience and skills of pathologists and has a subjective tendency, which is easy to produce differences within and among observers. In addition to the aforementioned technical shortcomings, the high cost of tissue biopsies limits widespread application. HVPG measures the pressure difference between the portal vein and the intra-abdominal vena cava by comparing the difference between the wedge pressure of the hepatic vein and the free pressure of the hepatic vein. Compared to the wedge pressure of the hepatic vein, the pressure gradient of the hepatic vein eliminates the influence of intra-abdominal pressure on the measurement results and therefore better reflects the pressure of the portal vein. However, in prehepatic or intrahepatic presinusoidal portal hypertension, the wedge pressure of the hepatic vein cannot reflect the increase in portal vein pressure as the blood flowing to the hepatic vein travels through the unaffected sinuses with a large volume and low resistance. Therefore, the hepatic vein wedge and pressure were normal in these patients. Portal hypertension caused by advanced schistosomiasis does not cause changes in wedge pressure or free pressure of the hepatic vein. Therefore, HVPG may not be effective in diagnosing and monitoring hepatic fibrosis in patients with advanced schistosomiasis. Considering these limitations, most studies have focused on noninvasive methods for detecting liver fibrosis. Serum markers can directly or indirectly reflect liver fibrosis. Studies have explored the diagnostic performance of individual and combinations of serum markers for the assessment of liver fibrosis in S. japonica (Supporting Information: Table 1). Hou et al. selected seven biomarkers to evaluate diagnostic efficacy and found that hyaluronic acid (HA) resulted in a high area under receiver operating characteristic curve (AUROC) of 0.938 (95% confidence interval [CI], 0.886–0.990) for significant fibrosis (F ≥ 2). Using a combination of aspartate aminotransferase and platelet ratio index and HA/100, the AUROC was 0.958 (95% CI, 0.914–1.000) for F ≥ 2.9 Another study constructed a new index using biomarkers to diagnose significant fibrosis. The international normalized ratio × HA/100 yielded a higher AUROC of 0.921 and therefore, the new index was considered a useful tool for identifying significant fibrosis in patients with schistosomiasis.10 However, serum markers have several limitations, including overestimating or underestimating the stage of fibrosis in certain conditions, as well as the inability to discriminate between intermediate stages of fibrosis. Due to the advantages of noninvasiveness and high repeatability, abdominal ultrasound plays an important role in the diagnosis of hepatosplenic schistosomiasis (Supporting Information: Figure 1). However, ultrasound is limited by the need for adequate experience and training, in addition to its low accuracy during the initial stages of the disease. Transient elastography (TE) is an ultrasound-based noninvasive technology for diagnosing liver fibrosis based on the assessment of liver stiffness measurement (LSM). The diagnostic value of LSM using TE for assessing liver fibrosis has been widely investigated in patients with various chronic liver diseases. A study showed that LSM is a reliable parameter for predicting significant to advanced liver fibrosis and cirrhosis in patients with advanced schistosomiasis japonica.5 LSM using TE is a noninvasive, convenient, and economical method for fibrosis risk evaluation; however, it has a few limitations. First, LSM cannot be accurately measured in patients with high body mass index or ascites because the mechanical waves cannot correctly propagate to the tissue. Moreover, TE evaluation does not allow the region of interest (ROI) to be placed in a specific area. Given the nature and distribution of fibrosis in HSS (fibrosis is not diffused by the liver parenchyma), LSM measured by TE will be subject to sampling error. Acoustic radiation force impulse elastography (point shear wave elastography, pSWE; two-dimensional shear wave elastography, 2DSWE) can also be used to diagnose HSS, enabling the detection of fibrosis in an ROI and yielding better diagnostic accuracy than conventional TE.11 A recent study that explored the application of pSWE in the context of schistosomiasis showed that pSWE was able to differentiate between mild and significant PPF at higher velocities (1.40 m/s).12 With the application of artificial intelligence technology in the medical field, an emerging technology called radiomics that is widely used in disease diagnosis can provide the automated quantification of image features from a large number of medical images. A recent prospective multicenter study investigating the diagnostic performance of the newly developed deep learning radiomics of elastography (DLRE) in 2D-SWE images for liver fibrosis staging in patients with HBV infection showed that DLRE was more accurate than 2D-SWE in assessing cirrhosis and advanced fibrosis, and more accurate than biomarkers in assessing all three liver fibrosis stages in patients with CHB.13 However, no studies on the use of radiomics technology have been conducted to evaluate periportal fibrosis caused by schistosomiasis. Although the noninvasive diagnosis of PPF has been extensively explored, there is still a lack of accepted and easy-to-use standards. Future studies should focus on establishing the role of noninvasive techniques in the diagnosis of liver fibrosis in schistosomiasis japonica, identifying fibrosis regression following antiparasitic therapy, and predicting the progression of the disease. Tao Wang and Kun Yang drafted the manuscript. HaiYong Hua, JianFeng Zhang, Wei Li, and Kun Yang critically revised the manuscript for important intellectual content. All the authors have read and approved the final version of the manuscript. This study was funded by the National Natural Science Foundation of China (Grant No.: 82173586) and Jiangsu Provincial Department of Science and Technology (Grant No.: BZ2020003). The authors declare no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Meta-analysis of the diagnostic accuracy of serum type IV collagen 7S concentration for the staging of liver fibrosis in nonalcoholic fatty liver disease.

We aimed to evaluate the diagnostic accuracy of the measurement of serum type IV collagen 7S (T4C7S) concentration for the staging of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A systematic search or published works was carried out using the PubMed, Cochrane Library, and Web of Science Core Collection databases for studies of the accuracy of serum T4C7S concentration for the staging of fibrosis using Fibrosis stage (F)0-4 in patients with NAFLD diagnosed by liver biopsy. Nine articles describing 1475 participants with NAFLD were included. For fibrosis≥F1, with n=849, summary estimates of sensitivity of 0.79, specificity of 0.69, and area under the curve (AUC) of 0.80 were obtained using a median T7C4S cut-off value of 4.6ng/ml. For fibrosis≥F2, with n=1,090, summary estimates of sensitivity of 0.78, specificity of 0.78, and AUC of 0.84 were obtained using a median cut-off value of 4.9ng/ml. For fibrosis≥F3, with n=1311 participants and a median cut-off value of 5.4ng/ml, a pooled sensitivity of 0.82, specificity of 0.81, and AUC of 0.83 were obtained. For fibrosis≥F4, with n=753 and a median cut-off value of 6.6ng/ml, a pooled sensitivity of 0.85, specificity of 0.81, and AUC of 0.85 were obtained. Serum T4C7S concentration was found to be an accurate method of staging liver fibrosis in patients with NAFLD.

S1228 EUS-Guided Shear Wave Elastography Appears to Be More Accurate Than Transient Elastography in Predicting Liver Fibrosis Staging in Patients With Obesity

Introduction: Transient elastography (TE) is a non-invasive clinical tool used to assess liver stiffness measurement (LSM) and can be correlated to liver fibrosis staging. Obesity can make elastography challenging to perform due to increased abdominal wall thickness, with high failure rates for TE. Fibroscan XL probes have lower failure rates, though it is unclear if readings are reliable or correlate well with liver biopsies. EUS guided shear wave elastography (EUS-SWE) can potentially circumvent this limitation, as liver parenchyma via EUS can be visualized under a thin subcentimeter gastric or duodenal wall, which does not change appreciably with body habitus. We aim to determine whether TE or EUS-SWE correlate better with liver biopsy fibrosis staging for patients with obesity. Methods: A retrospective chart review was performed for patients with obesity at a single tertiary hospital from Dec 2021 to May 2022. Patients with obesity (BMI≥30) with LSM concerning for advanced fibrosis (F3 or F4) were referred for EUS-SWE and EUS guided liver biopsy, both of which performed in the left liver lobe. LSM (reported in kPa) were correlated with fibrosis staging on liver biopsy and were considered accurate if they fell within cutoff ranges: kPa ≤7 = F0-1, kPa 7-8 = F2, kPa 8-12 = F3, and kPa >12 = F4. No established cutoffs exist for EUS-SWE, so stiffness values were compared to that for TE on which were closer to TE cutoff ranges. Results: 12 consecutive patients with obesity underwent TE, EUS-SWE, and EUS guided liver biopsy. The mean age was 55.3 [range 18-69], 9 (75%) were females, and mean BMI was 44.9 [range 30.2-67.8]. LSM ranged from 9.1 to 41.9 kPa. Only 2 (17%) patients’ TE results correlated accurately with liver fibrosis staging on biopsy; see Table. Assuming similar fibrosis staging cutoff ranges for TE, EUS-SWE accurately downgraded 8 (67%) patients and demonstrated no change for 4 (33%) patients. EUS-SWE was closer to biopsy LSM cutoffs for 9 (75%) patients, while TE was more accurate in only 1 (8%) patient. Conclusion: In this small cohort of patients with obesity with possible advanced fibrosis, TE appeared to overdiagnose fibrosis stage, while EUS-SWE appeared to downgrade LSM appropriately for patients who were overdiagnosed. Larger cohort studies are ongoing to allow proper interpretation of EUS-SWE stiffness values and compare its utility and accuracy to TE. Table 1. - Individual patient data with basic demographics, transient elastography data, EUS shear wave elastography data, and data comparison and analysis Patient # Age Gender BMI TE LSM Value (kPa) Fibrosis Staging Based on TE Cutoff Fibrosis Stage on Biopsy (TE cutoffs) TE LSM as Compared to Fibrosis Staging on Biopsy EUS-SWE Stiffness (kPa) Closer to Biopsy Cutoffs? TE vs EUS-SWE How Did EUS-SWE Compare to TE via Fibrosis Staging ? 1 58 Female 62.4 9.1 F3 F0 (kPa≤7mmHg) Overstaged 5 EUS-SWE Downgraded 2 68 Female 39 9.9 F3 F0 (≤7) Overstaged 4.9 EUS-SWE Downgraded 3 59 Female 32.6 9.4 F3 F0 (≤7) Overstaged 6.3 EUS-SWE Downgraded 4 63 Female 32.8 15.7 F4 F0 (≤7) Overstaged 7.3 EUS-SWE Downgraded 5 48 Male 67.8 41.9 F4 F0 (≤7) Overstaged 7.3 EUS-SWE Downgraded 6 63 Female 38 9.4 F3 F0 (≤7) Overstaged 2 EUS-SWE Downgraded 7 56 Male 43.6 9.6 F3 F3 (8-12) Appropriate Stage 10.5 EUS-SWE No Change 8 18 Female 61.1 34.6 F4 F2 (7-8) Overstaged 19.6 EUS-SWE Downgraded 9 53 Female 32.6 20.5 F4 F4 (≥12) Appropriate Stage 21.7 Same No change 10 55 Male 34.9 12.2 F4 F2 (7-8) Overstaged 12.2 Same No Change 11 53 Female 30.2 14 F4 F3 (8-12) Overstaged 15.2 TE No Change 12 69 Female 64.1 14.7 F4 F2 (7-8) Overstaged 10.2 EUS-SWE Downgraded

Radiomics nomograms based on R2* mapping and clinical biomarkers for staging of liver fibrosis in patients with chronic hepatitis B: a single-center retrospective study.

To investigate the value of R2* mapping-based radiomics nomograms in staging liver fibrosis in patients with chronic hepatitis B. Between January 2020 and December 2020, 151 patients with chronic hepatitis B were randomly divided into training (n = 103) and validation (n = 48) cohorts. From January to February 2021, 58 patients were included in a test cohort. Radiomics features were selected using the interclass correlation coefficient and least absolute shrinkage and selection operator method. Three radiomics nomograms, combining the radiomics score (Radscore) derived from R2* mapping and clinical variables, were used for staging significant and advanced fibrosis, and cirrhosis. Performance of the model was evaluated using the AUC. The utility and clinical benefits were evaluated using the continuous net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). The Radscore calculated by 12 radiomics features and independent factors (laminin and platelet) of advanced fibrosis were used to construct the radiomics nomograms. In the test cohort, the AUCs of the radiomics nomograms for staging significant fibrosis, advanced fibrosis, and cirrhosis were 0.738 (95% confidence interval [CI]: 0.604-0.872), 0.879 (95% CI: 0.779-0.98), and 0.952 (95% CI: 0.878-1), respectively. NRI, IDI, and DCA confirmed that radiomics nomograms demonstrated varying degrees of clinical benefit and improvement for advanced fibrosis and cirrhosis, but not for significant fibrosis. Radiomics nomograms combined with R2* mapping-based Radscore, laminin, and platelet have value in staging advanced fibrosis and cirrhosis but limited value for staging significant fibrosis. • Laminin and platelets were independent predictors of advanced fibrosis. • Radiomics analysis based on R2* mapping was beneficial for evaluating advanced fibrosis and cirrhosis. • It was difficult to distinguish significant fibrosis using a radiomics nomogram, which is possibly due to the complex pathological microenvironment of chronic liver diseases.

Diagnostic Performance of Transient Elastography Versus Two-Dimensional Shear Wave Elastography for Liver Fibrosis in Chronic Viral Hepatitis: Direct Comparison and a Meta-Analysis.

Objective This systematic review and meta-analysis aimed to compare the diagnostic performance of transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE) for staging liver fibrosis in patients with chronic viral hepatitis (CVH). Methods Pubmed, Embase, Web of Science, and Cochrane Library were searched (-01/08/2021) for studies comparing TE with 2D-SWE in patients with CVH. Other etiologies of chronic liver disease (CLD) and articles not published in SCI journals were excluded. The bivariate random-effects model was used to pool the performance of the TE and 2D-SWE. Results Eight articles with a total of 1301 CVH patients were included. The prevalence of significant fibrosis (fibrosis stage ≥ 2), advanced fibrosis (fibrosis stage ≥ 3), and cirrhosis was 50.8%, 44.8%, and 34.7%, respectively. 2D-SWE expressed higher overall accuracy than TE in detecting significant fibrosis (0.93 vs. 0.85, P = 0.04). No significant difference among the overall diagnostic accuracy of TE and 2D-SWE in staging advanced fibrosis and cirrhosis was found. Conclusion TE and 2D-SWE express good to excellent diagnostic accuracies to stage fibrosis in CVH patients. 2D-SWE compares favorably with TE especially for predicting significant fibrosis.

Rethinking Liver Fibrosis Staging in Patients with Hepatocellular Carcinoma: New Insights from a Large Two-Center Cohort Study.

BackgroundHepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy closely related to background chronic liver disease. This study aimed to explore predictive factors associated with background liver fibrosis burden in patients with HCC and sought to construct a practical predictive model for clinical use.MethodsThis large two-center retrospective cohort study evaluated data from Chinese medical centers. Uni- and multivariate ordinal logistic regression analyses were performed to identify variables associated with liver fibrosis stages. Predictive models based on variables identified by multivariate analysis were established in the Derivation Cohort and subjected to internal and external validation. Model performance was evaluated for discriminative and calibration abilities.ResultsMultivariate ordinal logistic regression analysis identified liver fibrosis severity score (LFSS), portal hypertension (PH) severity, plateletcrit (PCT) and model for end-stage liver disease-sodium (MELD-Na) as independent predictors of liver fibrosis stage in HCC patients. Nomograms that integrated these factors disclosed that the area under receiver operating characteristic curves (AUROCs) to predict S1 in the Derivation and External Validation cohorts were 0.850 and 0.919, respectively. Internal validation disclosed C-indexes of 0.823 and 0.833 in the Derivation and External Validation cohorts, respectively, indicating that the nomogram had good and excellent performance for distinguishing between S1 and non-S1 patients. Nomogram performance in the Derivation and External Validation cohorts, respectively, was fair and good to predict stage S2 (AUROCs 0.726, 0.806; C-indexes 0.713, 0.791); poor for S3 (AUROCs 0.648, 0.698; C-indexes 0.616, 0.666); good for S4 (AUROCs 0.812, 0.824; C-indexes 0.804, 0.792); and good for S3+S4 (AUROCs 0.806, 0.840; C-indexes 0.795, 0.811).ConclusionWe propose new predictive models for the staging of background liver fibrosis in patients with HCC that can be implemented into clinical practice as important complements to hepatic imaging to inform HCC management strategy.

FRI095 - Confounding factors in diagnostic performance of magnetic resonance elastography for staging liver fibrosis in patients with non-alcoholic fatty liver disease: an individual patient data meta-analysis

FRI095 - Confounding factors in diagnostic performance of magnetic resonance elastography for staging liver fibrosis in patients with non-alcoholic fatty liver disease: an individual patient data meta-analysis

Withdrawn: Bing‐Tian Dong, Yu‐Ping Chen, Guo‐Rong Lyu, Hua‐Ming Wang, Guo‐Fu Lin and Jiong‐Hui Gu; Diagnostic accuracy of two‐dimensional shear wave elastography and magnetic resonance elastography for staging liver fibrosis in patients with chronic hepatitis B: A systematic review and meta‐analysis

An accurate assessment of liver fibrosis is critical for the management of chronic hepatitis B (CHB) patients. Two-dimensional shear wave elastography (2D-SWE) and magnetic resonance elastography (MRE) have recently been proposed to diagnose liver fibrosis. To determine the optimal noninvasive method for diagnosing fibrosis in CHB, we conducted a meta-analysis to compare the performance of 2D-SWE and MRE for diagnosing fibrosis in patients with CHB. Literature databases were searched until January 1st 2021. Three measures, the summary area under the receiver operating characteristic curve (AUSROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities, were used to assess the performance of 2D-SWE and MRE for detecting liver fibrosis. Twenty-four studies with 5126 CHB patients were included. The summary sensitivities and specificities of 2D-SWE and MRE were 82% and 81%, 91% and 94%, respectively, for detecting significant fibrosis, 88% and 85%, 93% and 93%, respectively, for detecting advanced fibrosis, and 89% and 87%, 92% and 92%, respectively, for detecting cirrhosis. The AUSROC value of MRE (0.97) in predicting significant fibrosis was significantly higher than those of 2D-SWE (0.88, P < 0.001). The AUSROC values of 2D-SWE and MRE were 0.93 and 0.98, respectively, for the diagnosis of advanced fibrosis, and 0.94 and 0.97, respectively, for the diagnosis of cirrhosis. MRE and 2D-SWE are excellent tools for staging fibrosis in patients with CHB. MRE probably exhibit the better diagnostic accuracy in detecting significant fibrosis as compared to 2D-SWE.

Comparison of point-shear wave elastography (ElastPQ) and transient elastography (FibroScan) for liver fibrosis staging in patients with non-alcoholic fatty liver disease.

ElastPQ is a point shear wave elastography technique used to non-invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F-TE) in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F-TE and ElastPQ as part of routine clinical care. We enrolled 671 patients with NAFLD, mean age 55.8 ± 13 years, body mass index (BMI) 31.5 ± 5.7kg/m2 , 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F-TE (Spearman's r=0.80, p < .001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2kPa discrepancy between the two techniques were a larger waist circumference and F-TE ≥10kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F-TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F ≥ 1, F ≥ 2, F ≥ 3 and F=4 respectively). Optimal cut-off values of ElastPQ for individual fibrosis stages were lower than those of F-TE. ElastPQ shows an excellent correlation with F-TE in patients with NAFLD, which was better for lower LSM. The optimal cut-off values of ElastPQ are lower than those of F-TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F-TE for all stages of fibrosis.

Ultrasound score combined with liver stiffness measurement by sound touch elastography for staging liver fibrosis in patients with chronic hepatitis B: a clinical prospective study.

BackgroundA noninvasive and precise diagnosis of liver fibrosis in patients with chronic hepatitis B (CHB) is crucial for establishing the optimal time and strategy of therapy and for predicting treatment response. This study aimed to assess the diagnostic performance of ultrasound (US) score and liver stiffness measurement (LSM) of sound touch elastography (STE) in diagnosing liver fibrosis stages and to investigate whether combining these methods would improve liver fibrosis staging.MethodsUS and STE examinations were performed in CHB patients included. Liver biopsy was used as a reference standard. A diagnostic marker with the optimal linear combination (LC) of US score and LSM of STE, namely LC marker, was established for noninvasive assessment of liver fibrosis stages. The diagnostic performance of the LC marker was evaluated by using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC).ResultsA total of 291 subjects, including 242 patients with CHB and 49 healthy volunteers, were included. Correlation analysis showed that the correlation of liver fibrosis stages to the LC marker (Spearman’s r=0.846, P<0.001) was higher than that of LSM (r=0.771, P<0.001) or US score (r=0.825, P<0.001) alone. The results showed that the overall diagnostic performance of the LC marker in predicting a fibrosis stage of ≥F1, ≥F2, ≥F3, and =F4 {AUCs: 0.943 [95% confidence interval (CI): 0.917–0.948], 0.906 (0.871–0.915), 0.953 (0.923–0.969), and 0.961 (0.922–0.973), respectively} were better than those of the US score [AUCs: 0.916 (0.883–0.948, P=0.014), 0.875 (0.835–0.915, P<0.001), 0.934 (0.898–0.969, P=0.001), and 0.918 (0.864–0.973, P<0.001), respectively] or LSM [AUCs: 0.858 (0.812–0.948, P<0.001), 0.867 (0.826–0.915, P=0.006), 0.930 (0.894–0.969, P<0.023), and 0.958 (0.918–0.973, P=0.778), respectively].ConclusionsThe LC marker with the optimal combination of LSM and US score may be considered as a promising diagnostic model for noninvasive staging of liver fibrosis.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort.

to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy. Histological inflammation and surrogate biomarkers of inflammation can overestimate liver stiffness, but only GGT was statistically significant in the multivariate analysis. Important features of NAFLD patients such as obesity, DM, or lipidic profile did not affect MRE accuracy.

Rethinking Liver Fibrosis Staging in Patients with Hepatocellular Carcinoma: New Insights from a Large Multi-Center Cohort Study

Rethinking Liver Fibrosis Staging in Patients with Hepatocellular Carcinoma: New Insights from a Large Multi-Center Cohort Study

Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study

Non-alcoholic steatohepatitis (NASH) is a chronic, progressive fibrotic liver disease that can lead to cirrhosis. While liver biopsy is considered the reference standard for the histologic diagnosis of NASH and staging of fibrosis, its use in clinical practice is limited. Non-invasive tests (NITs) are increasingly being used to identify and stage liver fibrosis in patients with NASH, and several can assess liver-related outcomes. We report changes in various NITs in patients treated with obeticholic acid (OCA) or placebo in the phase III REGENERATE study. Patients with NASH and fibrosis stage F2 or F3 (n= 931) were randomized (1:1:1) to receive placebo, OCA 10 mg, or OCA 25 mg once daily. Various NITs based on clinical chemistry and/or imaging were evaluated at baseline and throughout the study. Rapid, sustained reductions from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase levels, as well as in Fibrosis-4 (FIB-4), FibroTest, FibroMeter, and FibroScan-AST scores were observed in OCA-treated vs. placebo-treated patients. Reduction in liver stiffness by vibration-controlled transient elastography was observed in the OCA 25 mg group vs. the placebo group at Month 18. NIT changes were associated with shifts in histologic fibrosis stage. The greatest improvements were observed in patients with ≥1-stage fibrosis improvement; however, improvements in ALT, AST, FIB-4, and FibroTest were also observed in OCA-treated patients whose histologic fibrosis remained stable. Based on the REGENERATE Month 18 interim analysis, rapid and sustained improvements in various NITs were observed with OCA treatment. Dynamic changes in selected NITs separated histologic responders from non-responders. These results suggest that NITs may be useful in assessing histologic response to OCA therapy. CLINICALTRIALS. NCT02548351 LAY SUMMARY: Non-alcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, non-invasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study, which is evaluating the effects of obeticholic acid vs. placebo in patients with NASH, various NITs were also evaluated. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients' response to therapy.