GOOD CORRELATION BETWEEN LIVER STIFFNESS MEASUREMENT AND APRI, FIB-4, PLATELET COUNT, IN PEDIATRIC AUTOIMMUNE HEPATITIS.

BACKGROUND: •Due to the invasive nature of the liver biopsy, there is a growing interest in the use of non-invasive markers of liver fibrosis. BACKGROUND: •There is a significant and positive correlation between APRI. BACKGROUND: FIB-4 and platelet count and liver stiffness measurement evaluated by transient elastography in pediatric autoimmune hepatitis. BACKGROUND: There is limited evidence focusing on the use of non-invasive markers to assess liver fibrosis in pediatric chronic liver diseases. OBJECTIVE: The aim of the study was to evaluate the correlation between liver stiffness measurement (LSM) using transient liver elastography (TLE) and serum non-invasive markers in pediatric autoimmune hepatitis (AIH). METHODS: Cross-sectional study between May 2016 and February 2020. Twenty-eight children with AIH (age range between 3 and 20 years old) who had undergone TLE and had routine serum tests were enrolled. Patients were divided into 2 groups: (1) Liver fibrosis degree ≥F2 (TLE ≥6.45 kPa) and (2)

Diagnostic accuracy of an uncorrected native T1 mapping sequence for liver fibrosis and inflammation in autoimmune hepatitis: a prospective study using histopathology as reference standard.

PURPOSE: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. MATERIAL AND METHODS: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3 months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. RESULTS: T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). CONCLUSION: A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Metavir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis.

BACKGROUND: Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. AIM: To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. METHODS: The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. RESULTS: A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. CONCLUSION: Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

A novel model predicted liver cirrhosis constructed by ultrasound and serological in autoimmune liver hepatitis.

To establish a noninvasive model based on two-dimensional shear wave elasticity (2D-SWE) technology, ultrasound feature and serological indicators to predict cirrhosis in autoimmune hepatitis (AIH) and verified. Patients with AIH confirmed by liver biopsy with liver ultrasound and serological examination were collected from January 2019 to May 2022. Patients were divided into cirrhosis and non-cirrhosis groups. Basic indexes, ultrasound indexes and serological indexes were collected. Multivariable logistic regression used for screening independent risk factors predicting cirrhosis, construct the AIH cirrhosis prediction model, named autoimmune hepatitis cirrhosis (AIHC). Determine best cutoff score according to the Youden index, verified the model's predictive efficacy. One hundred forty-six patients were collected. The following indicators were independent risk factors for predicting cirrhosis: LS (OR: 1.416, P = .015), splenomegaly (OR: 10.446, P = .006), complement C4 (OR: 0.020, P = .009). The best cutoff score was 65, with a sensitivity 88.9% and specificity 75.6%; the area under curve was 0.901, AIHC possessed a higher net reclassification index (NRI) and integrated discrimination improvement compared with other indexes, and AIHC had the best clinical decision curve. The AIHC constructed in this study has better predictive efficacy than other noninvasive indexes, and we visualized the model for easy application, which was worth further promotion in clinical practice.

Performance of 2D-shear wave elastography in autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

PURPOSE: To evaluate the diagnostic values of liver stiffness (LS) measured by 2D-SWE, fibrosis index based on the four factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and GGT to PLT ratio (GPR) for assessing liver fibrosis and high-risk esophageal varices (EVs) in patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome. METHODS: Data of 141 patients were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. The Spearman correlation coefficient was used for correlation analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance. RESULTS: LS and FIB-4 were positively correlated with the fibrosis stage (r = 0.555 and 0.198, respectively). LS had significantly higher areas under the ROC curves (AUROCs) values than FIB-4 for predicting advanced fibrosis (0.818 vs. 0.567, P < 0.001), cirrhosis (0.879 vs. 0.637, P < 0.001), whereas LS and FIB-4 similarly predicted significant fibrosis (0.748 vs. 0.638, P = 0.071) and high-risk EVs (0.731 vs. 0.659, P = 0.303). The optimal cut-off values of 2D-SWE for detecting significant fibrosis, advanced fibrosis, cirrhosis, and high-risk EVs were 8.7 kPa, 12.8 kPa, 14.0 kPa, and 11.0 kPa, respectively. LS values were influenced by fibrosis stage, serum GGT, albumin, and total bilirubin levels. The overall concordance rate of the liver stiffness vs. Scheuer stages was 49.65%. CONCLUSIONS: 2D-SWE shows significantly greater diagnostic accuracy than serum fibrosis indexes for diagnosing advanced fibrosis and cirrhosis in patients with AIH-PBC overlap syndrome.

Longitudinal changes in quantitative magnetic resonance imaging metrics in children and young adults with autoimmune liver disease.

PURPOSE: To assess longitudinal changes in quantitative MRI metrics in pediatric and young adult patients with autoimmune liver disease (AILD). METHODS: This prospective, IRB-approved study included 20 children and young adults (median age = 15 years) with primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC) and 19 (median age = 17 years) with autoimmune hepatitis (AIH). At a field strength of 1.5-T, T2*-corrected T1 mapping (cT1), 3D fast spin-echo MRCP, and 2D gradient recalled echo MR elastography (MRE) were performed at baseline, one year, and two years. cT1 and quantitative MRCP were processed using LiverMultiScan and MRCP + , respectively (Perspectum Ltd, Oxford, UK). Linear mixed models were used to assess longitudinal changes in quantitative MRI metrics. Spearman rank-order correlation was used to assess relationships between changes in quantitative MRI metrics. RESULTS: Changes in quantitative MRI metrics greater than established repeatability coefficients were measured in six (cT1) and five (MRE) patients with PSC/ASC as well as in six patients (cT1 and MRE) with AIH, although linear mixed models identified no significant changes for the subgroups as a whole. For PSC/ASC, there were positive correlations between change in liver stiffness and changes in bile duct strictures (ρ = 0.68; p = 0.005) and bile duct dilations (ρ = 0.70; p = 0.004) between baseline and Year 2. CONCLUSION: On average, there were no significant changes in quantitative MRI metrics over a two-year period in children and young adults with AILD. However, worsening cholangiopathy was associated with increasing liver stiffness by MRE in patients with PSC/ASC.

[Malignant lymphoma diagnosed by gallbladder wall thickness in an autoimmune hepatitis patient].

A 77-year-old female patient was undergoing steroid treatment for cirrhosis with autoimmune hepatitis. Periodic imaging acquisitions revealed both irregular gallbladder wall thickness and an isovascular tumor in segment one of the liver. After cholecystectomy and segmental hepatectomy, the pathological diagnosis was diffuse large B-cell lymphoma in both organs. Accordingly, she received chemotherapy but the disease rapidly spread;she died five months after surgery. Malignant lymphoma of the gallbladder is an uncommon disease;we consider that autoimmunity factors were associated with this pathogenesis.

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

BACKGROUND: Autoimmune 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. AIM: To 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. METHODS: A 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. RESULTS: LS 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). CONCLUSION: LS 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.

Associations between MRI T1 mapping, liver stiffness, quantitative MRCP, and laboratory biomarkers in children and young adults with autoimmune liver disease.

PURPOSE: Define relationships between quantitative magnetic resonance imaging (MRI) metrics and clinical/laboratory data in a pediatric and young adult cohort with autoimmune liver disease (AILD). MATERIALS AND METHODS: This prospective, cross-sectional study was institutional review board-approved. Patients enrolled in an institutional AILD registry were divided into groups: (1) autoimmune hepatitis (AIH) or (2) primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC). Participants underwent serum liver biochemistry testing and research MRI examinations, including 3D magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and iron-corrected T1 mapping (cT1). MRCP + and LiverMultiScan (Perspectum Ltd., Oxford, UK) were used to post-process 3D MRCP and cT1 data. Multiple linear regression models were used to assess relationships. RESULTS: 58 patients, 35 male, median age 16 years were included; 30 in the AIH group, 28 in the PSC/ASC group. After statistical adjustments for patient age, sex, presence of inflammatory bowel disease (IBD), specific diagnosis (PSC/ASC vs. AIH), and time from diagnosis to MRI examination, left hepatic bile duct maximum diameter was a statistically significant predictor of whole liver mean cT1, cT1 interquartile range (IQR), and MRE liver stiffness (p = 0.01-0.04). Seven laboratory values were significant predictors of whole liver cT1 IQR (p < 0.0001-0.04). Eight laboratory values and right hepatic bile duct median and maximum diameter were significant predictors of liver stiffness (p < 0.0001-0.03). CONCLUSIONS: Bile duct diameters and multiple laboratory biomarkers of liver disease are independent predictors of liver stiffness and cT1 IQR in pediatric patients with AILD.

Quantitative multiparametric MRI as a non-invasive stratification tool in children and adolescents with autoimmune liver disease.

Autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC) are two very closely related autoimmune liver diseases with overlapping clinical features and similar management strategies. The purpose of this study was to assess the utility of quantitative imaging markers to distinguish ASC from AIH in paediatrics. 66 participants (N = 52 AIH, N = 14 ASC) aged 14.4 ± 3.3 years scheduled to undergo routine biopsy and baseline serum liver biochemistry testing were invited to undergo MRI (non-contrast abdominal MRI and 3D fast spin-echo MRCP). Multiparametric MRI was used to measure fibro-inflammation with corrected T1 (cT1), while the biliary tree was modelled   using quantitative MRCP (MRCP +). Mann-Whitney U tests were performed to compare liver function tests with imaging markers between patient groups (ASC vs AIH). Receiver operating characteristic curves and stepwise logistic regressions were used to identify the best combination of markers to discriminate between ASC and AIH. Correlations between liver function tests and imaging markers were performed using Spearman's rank correlation. cT1 was significantly correlated with liver function tests (range 0.33 ≤ R ≤ 56, p < 0.05), as well as with fibrosis, lobular and portal inflammation (range 0.31 ≤ R ≤ 42, p < 0.05). 19 MRCP + metrics correlated significantly with liver function tests (range 0.29 ≤ R ≤ 0.43, p < 0.05). GGT and MRCP + metrics were significantly higher in ASC compared to those with AIH. The best multivariable model for distinguishing ASC from AIH included total number of ducts and the sum of relative severity of both strictures and dilatations AUC: 0.91 (95% CI 0.78-1). Quantitative MRCP metrics are a good discriminator of ASC from AIH.

Bone microarchitecture in patients with autoimmune hepatitis.

In patients with autoimmune hepatitis (AIH), osteoporosis represents a common extrahepatic complication, which we recently showed by an assessment of areal bone mineral density (aBMD) via dual-energy x-ray absorptiometry (DXA). However, it is well established that bone quality and fracture risk does not solely depend on aBMD, but also on bone microarchitecture. It is currently not known whether AIH patients exhibit a site-specific or compartment-specific deterioration in the skeletal microarchitecture. In order to assess potential geometric, volumetric, and microarchitectural changes, high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements were performed at the distal radius and distal tibia in female patients with AIH (n = 51) and compared to age-matched female healthy controls (n = 32) as well as to female patients with AIH/primary biliary cholangitis (PBC) overlap syndrome (n = 25) and female patients with PBC alone (PBC, n = 36). DXA at the lumbar spine and hip, clinical characteristics, transient elastography (FibroScan) and laboratory analyses were also included in this analysis. AIH patients showed a predominant reduction of cortical thickness (Ct.Th) in the distal radius and tibia compared to healthy controls (p < .0001 and p = .003, respectively). In contrast, trabecular parameters such as bone volume fraction (BV/TV) did not differ significantly at the distal radius (p = .453) or tibia (p = .508). Linear regression models revealed significant negative associations between age and Ct.Th (95% confidence interval [CI], -14 to -5 µm/year, p < .0001), but not between liver stiffness, cumulative prednisolone dose (even after an adjustment for age), or disease duration with bone microarchitecture. The duration of high-dose prednisolone (≥7.5 mg) was negatively associated with trabecular thickness (Tb.Th) at the distal radius. No differences in bone microarchitecture parameters between AIH, AIH/PBC, and PBC could be detected. In conclusion, AIH patients showed a severe age-dependent deterioration of the cortical bone microarchitecture, which is most likely the major contribution to the observed increased fracture risk in these patients. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Diagnostic accuracy of two-dimensional shear wave elastography in detecting hepatic fibrosis in children with autoimmune hepatitis, biliary atresia and other chronic liver diseases.

BACKGROUND: Although fibrosis is the main determinant of liver stiffness, other disease-related factors usually disregarded in studies on liver elastography, such as inflammation and cholestasis, may influence liver stiffness. OBJECTIVE: To evaluate the accuracy of two-dimensional (2-D) shear wave elastography in assessing liver fibrosis in children with chronic liver disease by controlling for the confounding role of several disease- and patient-related factors. MATERIALS AND METHODS: Three disease groups were studied: 1) various chronic liver diseases, 2) autoimmune hepatitis and 3) biliary atresia. The METAVIR (meta-analysis of histological data in viral hepatitis) score was used for fibrosis staging and grading of necroinflammatory activity. Multiple linear regression was used to evaluate the relationship between liver stiffness measurements and disease-related factors. The diagnostic accuracy of elastography for predicting fibrosis stages was assessed by calculating the area under the receiver operating characteristic curves. RESULTS: The various chronic liver diseases group (n=32; 7.1±4.9 [mean±standard deviation] years) showed liver stiffness of 8.9±5.0 (mean±standard deviation) kPa, the autoimmune hepatitis group (n=33; 8.1±4.4 years) of 7.1±2.7 kPa, and the biliary atresia group (n=19; 0.2±0.1 years) of 19.7±15.2 kPa. Liver stiffness measurements differed across METAVIR fibrosis categories in all disease groups. The highest values were found in biliary atresia, at fibrosis stages ≥F2 (F2: 12.4±1.6 kPa, F3: 17.8±2 kPa, F4: 41.5±12.4 kPa). Liver stiffness was strongly associated only with fibrosis (P<0.0001) in various chronic liver diseases, but with necroinflammatory activity (P<0.0001) and fibrosis (P=0.002) in autoimmune hepatitis, and with age (P<0.0001), fibrosis (P<0.0001) and cholestasis (P=0.009) in biliary atresia. Optimal cutoffs for detecting advanced fibrosis (≥F3) were 16 kPa (area under curve: 0.98; sensitivity: 87.5%; specificity: 96.7%) in biliary atresia and 8.7 kPa (area under curve: 0.98; sensitivity: 93.8%; specificity: 96.1%) in other chronic liver diseases. CONCLUSION: Two-dimensional shear wave elastography is reliable in assessing liver fibrosis in children with chronic liver diseases.

Autoimmune hepatitis in practice, from diagnosis to complications: What is the role of imaging? A clinicoradiological review.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown origin that can lead to liver cirrhosis, hepatocellular carcinoma (HCC), liver transplantation or death. The diagnosis is performed upon a multifactorial score. Treatment is based on the combination of immunosuppressants and aims at clinical, laboratory and histological remission, the latter being the most difficult to be achieved and proven. The absence of liver inflammation, defined by biopsy, is the main determinant in remission or therapeutic modification. Imaging exams have a limited role in this clinical management and the main findings are those related to chronic liver disease. Imaging's relevance, therefore, lies mainly in helping to exclude overlapping syndromes and in assessing complications related to cirrhosis, such as in screening for HCC. In recent years, however, the radiological literature has been witnessing increasing advances with regard to imaging biomarkers in liver disease, leading some authors to consider a future of virtual liver biopsy performed by magnetic resonance imaging. The present study aims to review the role of imaging in the management of AIH in the light of recent advances in the current literature and to provide an illustrated guide with the main findings described in the disease.

Multiparametric MRI as a Noninvasive Monitoring Tool for Children With Autoimmune Hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is a progressive liver disease managed with corticosteroids and immunosuppression and monitored using a combination of liver biochemistry and histology. However, liver biopsy is invasive with risk of pain and bleeding. The aim of the present study was to investigate the utility of noninvasive imaging with multiparametric magnetic resonance imaging (MRI) (mpMRI) to provide clinically useful information on the presence and extent of hepatic inflammation, potentially guiding immunosuppression. METHODS: Eighty-one participants (aged 6-18), 21 healthy and 60 AIH patients, underwent multiparametric MRI to measure fibro-inflammation with iron-corrected T1 (cT1) at the Children's Memorial Health Institute in Warsaw alongside other clinical blood tests and liver biopsy at recruitment and after an average of 16-month follow-up (range 9-22 months). Correlation analyses were used to investigate the associations between cT1 with blood serum markers and histological scores. RESULTS: At recruitment, patients with AIH had a higher cT1 value than healthy controls (P < 0.01). cT1 correlated significantly with key histopathological features of disease. Treatment naïve AIH patients showed evidence of inflammation and heterogeneity across the liver compared to healthy controls.At follow-up, cT1 showed utility in monitoring disease regression as most patients showed significantly reduced fibro-inflammation with treatment (P < 0.0001) over the observational period. Six patients had histological fibrosis and clear fibro-inflammation on MR despite biochemical remission (normalized aspartate aminotransferase (AST), alanine aminotransferase (ALT), and immunoglobulin G [IgG]). CONCLUSIONS: Multiparametric MRI can measure disease burden in pediatric AIH and can show changes over time in response to therapy. Active disease can be seen even in biochemical remission in children.

Non-invasive assessment of liver fibrosis in autoimmune hepatitis: Diagnostic value of liver magnetic resonance parametric mapping including extracellular volume fraction.

PURPOSE: Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that leads to severe fibrosis and cirrhosis. The aim of this study was to determine the diagnostic value of T1 and T2 mapping as well as extracellular volume fraction (ECV) for non-invasive assessment of liver fibrosis in AIH patients. METHODS: In this prospective study, 27 patients (age range: 19-77 years) with AIH underwent liver MRI. T1 and T2 relaxation times as well as ECV were quantified by mapping techniques. The presence of significant fibrosis (≥ F2) was defined as magnetic resonance elastography (MRE)-based liver stiffness ≥ 3.66 kPa. MRE was used as reference standard, against which the diagnostic performance of MRI-derived mapping parameters was tested. Diagnostic performance was compared by utilizing receiver-operating characteristic (ROC) analysis. RESULTS: MRE-based liver stiffness correlated with both, hepatic native T1 (r = 0.69; P < 0.001) as well as ECV (r = 0.80; P < 0.001). For the assessment of significant fibrosis, ECV yielded a sensitivity of 85.7% (95% confidence interval (CI): 60.1-96.0%) and a specificity of 84.6% (CI 60.1-96.0%); hepatic native T1 yielded a sensitivity of 85.7% (CI 60.1-96.0%); and a specificity of 76.9% (CI 49.7-91.8%). Diagnostic performance of hepatic ECV (area under the curve (AUC): 0.885), native hepatic T1 (AUC: 0.846) for assessment of significant fibrosis was similar compared to clinical fibrosis scores (APRI (AUC: 0.852), FIB-4 (AUC: 0.758), and AAR (0.654) (P > 0.05 for each comparison)). CONCLUSION: Quantitative mapping parameters such as T1 and ECV can identify significant fibrosis in AIH patients. Future studies are needed to explore the value of parametric mapping for the evaluation of different disease stages.

FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases.

INTRODUCTION AND OBJECTIVES: We assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], in order to assess new potential non-invasive biomarkers of liver fibrosis in patients with ALD, as similar data are missing. PATIENTS AND METHODS: The following groups were included: group 1: n = 78 AIH; group 2: n = 56 PBC. FMvirus and FMVCTE were determined in all 134 patients who underwent liver biopsy and TE the same day with sera collection. In addition, APRI and FIB-4 scores were calculated. RESULTS: The AUCs for TE and FMVCTE were significantly better (0.809; p < 0.001 and 0.772; p = 0.001, respectively for AIH and 0.997; p < 0.001 and 1; p < 0.001, for PBC) than the other three markers in predicting ≥ F3 fibrosis irrespective of the biochemical activity. FMVCTE and TE had good diagnostic accuracy (75.6% and 73%, respectively) for predicting severe fibrosis in AIH and performed even better in PBC (94.6% and 96.4%, respectively). The cut-offs of TE and FMVCTE had the best sensitivity and specificity in predicting ≥ F3 fibrosis in both AIH and PBC. CONCLUSIONS: FMVCTE seems to detect severe fibrosis equally to TE in patients with ALD but with better specificity. Biochemical disease activity did not seem to affect their diagnostic accuracy in ALD and therefore, could be helpful for the assessment of fibrosis, especially if they are performed sequentially (first TE with the best sensitivity and then FMVCTE with the best specificity).

Liver fibrosis with two-dimensional shear-wave elastography in patients with autoimmune hepatitis.

BACKGROUND: Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound-based real-time 2D-SWE imaging technique for noninvasive assessment of liver fibrosis. The diagnostic performance of 2D-SWE for assessing liver fibrosis in patients with autoimmune hepatitis (AIH) has not been reported. AIMS: To evaluate the diagnostic performance of 2D-SWE and serologic tests including the aspartate amino transferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) for liver fibrosis staging in patients with AIH. METHODS: 103 patients were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. The areas under the receiver operating characteristic curves (AUROCs) were used to assess the accuracy of 2D-SWE and serum fibrosis models for staging liver fibrosis. RESULTS: Liver stiffness measured by 2D-SWE had a strong correlation with histological fibrosis stage (r = 0.71, P < 0.0001). The AUROCs of liver stiffness in detecting significant fibrosis, severe fibrosis, and cirrhosis were 0.84, 0.84, and 0.94, respectively. The AUROCs of liver stiffness for detecting significant fibrosis and severe fibrosis were higher than those of APRI (0.57, 0.56) and FIB-4 (0.63, 0.66), respectively. The cut-off liver stiffness values for predicting significant fibrosis, severe fibrosis, and cirrhosis were 10.0, 15.8, and 19.3 kPa, respectively. CONCLUSIONS: 2D-SWE shows promising diagnostic performance for staging liver fibrosis in patients with AIH.

Differentiating pediatric autoimmune liver diseases by quantitative magnetic resonance cholangiopancreatography.

PURPOSE: Autoimmune liver diseases (AILD), including primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH), have overlapping clinical features but distinct management strategies and outcomes. The purpose of this study was to assess the diagnostic performance of quantitative magnetic resonance cholangiopancreatography (MRCP) parameters for distinguishing PSC/ASC from AIH in children and young adults. MATERIALS AND METHODS: This IRB-approved, cross-sectional study included participants from an institutional AILD registry that underwent baseline serum liver biochemistry testing and 3D fast spin-echo MRCP. The biliary tree was extracted and modeled from MRCP images using novel proprietary software (MRCP+ ™; Perspectum Diagnostics; Oxford, United Kingdom), and quantitative parameters were generated (e.g., biliary tree volume; number and length of bile ducts, strictures, and dilations; bile duct median/maximum diameters). Mann-Whitney U tests were performed to compare laboratory values and MRCP metrics between patient cohorts (clinical diagnosis of PSC/ASC versus AIH). Receiver operating characteristic (ROC) curves and multivariable logistic regression were used to assess diagnostic performance of serum biochemistry values and MRCP parameters for discriminating PSC/ASC from AIH. RESULTS: Thirty percent (14/47) of MRCP exams failed post-processing due to motion artifact. The remaining 33 patients included 20 males and 13 females, with a mean age of 15.1 ± 3.9 years. Eighteen patients were assigned the clinical diagnosis of PSC or ASC and 15 of AIH. All but one quantitative MRCP parameter were significantly different between cohorts (p < 0.05) and predictive of diagnosis (ROC p < 0.05), including numbers of bile duct strictures (area under curve [AUC] = 0.86, p < 0.0001) and dilations (AUC = 0.87, p < 0.0001) and total length of dilated ducts (AUC = 0.89, p < 0.0001). Laboratory values were not significantly different between cohorts (p > 0.05). The best multivariable model for distinguishing PSC/ASC from AIH included total length of dilated ducts (odds ratio [OR], 1.08; 95% CI 1.02-1.14) and maximum left hepatic duct diameter (OR, 1.21; 95% CI 0.57-2.56) [AUC = 0.92]. CONCLUSION: Quantitative MRCP parameters provide good discrimination of PSC/ASC from AIH.