Associations Between Hip Pathology, Hip and Groin Pain, and Injuries in Hockey Athletes: A Clinical Commentary.

Femoroacetabular impingement (FAI), particularly cam morphology, is highly prevalent among elite hockey athletes. Moreover, hip and groin pain has become a common issue in hockey, with approximately 50% of European professional athletes reported to experience a hip or groin problem during a season. While most athletes will not miss training or competition due to this, restricted competitive performance and increased risk of reduced physical and psychological well-being are likely. Recent research suggests that the development of cam morphology is related to the repetitive shear stresses experienced at the hip joint during adolescence from skating. This condition likely increases the potential for intra-articular and extra-articular injuries in these athletes later in their careers. Research also indicates that the hip joint mechanics during forward skating substantially increase the possibility of sustaining a labral tear compared to other sports. Such an injury can increase femoral head movement within the joint, potentially causing secondary damage to the iliofemoral ligament, ligamentum teres and joint capsule. These injuries and the high density of nociceptors in the affected structures may explain the high prevalence of hip and groin pain in hockey athletes. Compensatory adaptations, such as reduced hip strength, stability, and range-of-motion (ROM) likely increase the opportunity for core muscle injuries and hip flexor and adductor injuries. Specifically, the limited hip ROM associated with cam morphology appears to exacerbate the risk of these injuries as there will be an increase in pubic symphysis stress and transverse strain during rotational movements. It is hoped that this article will assist practitioners currently working with hockey athletes to develop evidence-informed monitoring strategies and training interventions, aimed at reducing the incidence and severity of hip and groin problems, ultimately enhancing athlete performance and well-being. Therefore, the purpose of this clinical commentary was to examine current evidence on common hip pathologies in hockey athletes, exploring potential associations between hip and groin pain and the biomechanics of hockey activities. Level of Evidence: 5.

Clonal haematopoiesis and risk of chronic liver disease.

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection.

BACKGROUND: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID. OBJECTIVES: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection. METHODS: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls. RESULTS: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months. CONCLUSION: CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID. TRIAL REGISTRATION NUMBER: NCT04369807.

Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study.

OBJECTIVES: To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation. DESIGN: Prospective cohort study. PARTICIPANTS: Individuals. METHODS: In individuals recovered from acute COVID-19, we assessed symptoms, health status, and multi-organ tissue characterisation and function. SETTING: Two non-acute healthcare settings (Oxford and London). Physiological and biochemical investigations were performed at baseline on all individuals, and those with organ impairment were reassessed. MAIN OUTCOME MEASURES: Primary outcome was prevalence of single- and multi-organ impairment at 6 and 12 months post COVID-19. RESULTS: A total of 536 individuals (mean age 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post COVID-19); 331 (62%) with organ impairment or incidental findings had follow-up, with reduced symptom burden from baseline (median number of symptoms 10 and 3, at 6 and 12 months, respectively). Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L < 0.7; 57% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single-organ impairment. Single- and multi-organ impairment were present in 69% and 23% at baseline, persisting in 59% and 27% at follow-up, respectively. CONCLUSIONS: Organ impairment persisted in 59% of 331 individuals followed up at 1 year post COVID-19, with implications for symptoms, quality of life and longer-term health, signalling the need for prevention and integrated care of long COVID.Trial Registration: ClinicalTrials.gov Identifier: NCT04369807.

Hip Strength Profiling of Ice Hockey Athletes Across Various Joint-Specific Angles: Monitoring and Injury Implications.

ABSTRACT: Secomb, JL, Kelly, M, and Dascombe, BJ. Hip strength profiling of ice hockey athletes across various joint-specific angles: monitoring and injury implications. J Strength Cond Res 37(7): e422-e429, 2023-The purpose of this research was to compare the hip adduction and abduction relative strength, adduction-to-abduction strength ratio (ADD:ABD), and interlimb asymmetries of ice hockey athletes between the typically used bilateral position and 3 unilateral positions in joint-specific angles (0°, 25°, and 50° of hip abduction) relevant to an ice hockey stride. A secondary purpose was to explore any relationships between these measures and hip and groin noncontact injuries, and self-reported pain and disability. Twenty-five semiprofessional male ice hockey athletes (26.7 ± 6.7 years) were assessed for hip abduction range of motion (ROM), hip adduction and abduction relative strength, and completed the Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaire. Within-subjects repeated-measures analysis of variance revealed a significant effect for the assessment position for adduction ( F1,24 = 52.4, p < 0.01) and abduction relative strength ( F1,24 = 152.1, p < 0.01), ADD:ABD ( F1,24 = 38.9, p < 0.01), and the interlimb asymmetries for each of these variables ( F1,24 = 9.8-12.3; p < 0.01), with large strength differences observed between the bilateral assessment and all unilateral assessment positions for adduction and abduction relative strength. In addition, 4 athletes experienced a noncontact hip or groin injury within 1 month after testing, and when compared with the rest of the cohort ( n = 21) with Welch's t -tests, demonstrated significantly reduced hip abduction ROM (mean difference [MD] = -8.4 ± 2.5°; p < 0.01), sport subscale score for the HAGOS questionnaire (MD = -33.9 ± 7.1; p < 0.01), and a decline in hip adduction relative strength in the unilateral position of 50° compared with the position of 25° hip abduction (MD = -13.4 ± 3.8; p = 0.04). These results suggest that practitioners working with ice hockey athletes may benefit from profiling hip strength in these unilateral joint-specific angle positions because they provide an evidence base to determine the hip strength needs of ice hockey athletes in positions associated with skating performance and noncontact hip and groin injury mechanisms (between 25° and 50° of hip abduction).

Quantitative MR in Paediatric Patients with Wilson Disease: A Case Series Review.

Wilson disease (WD) is a liver disorder characterized by improper copper metabolism. Although non-invasive tools are currently used to support diagnosis and management, this is still an area of unmet need, as patients present with a wide range of symptoms. Our aim was to investigate the potential utility of multiparametric magnetic resonance imaging (mpMRI) and quantitative magnetic resonance cholangiopancreatography (MRCP+) to support patient management. MRI examinations of 7 children and young adults aged 8-16 years (six at diagnosis) were performed alongside a standard of care clinical and histological examination. Images were quantitatively analyzed to derive metrics of liver (corrected T1 (cT1; fibro-inflammation), MR liver fat (proton density fat fraction; PDFF)), and biliary health (MRCP+). MRI-PDFF provided a more dynamic characterization of fat compared with that provided by ultrasound. Those with elevated histological scores of fibrosis, inflammation, and steatosis had elevated mpMRI values. MRCP+ managed to identify dilatations in the biliary tree which were not observed during the standard of care examination. mpMRI and MRCP+ metrics show early promise as markers to assess both liver and biliary health in Wilson disease. Investigations to understand and explore the utility of these markers are warranted and should be performed.

Precision medicine for liver tumours with quantitative MRI and whole genome sequencing (Precision1 trial): study protocol for observational cohort study.

INTRODUCTION: Radiogenomic analysis of patients being considered for liver resection is seldom performed in the clinic despite recent evidence indicating that quantitative MRI could improve posthepatectomy outcomes. Meanwhile, the increasingly accessible results from whole genome sequencing reporting on clinically actionable genetic biomarkers are yet to be fully integrated into the clinical care pathway. METHODS AND ANALYSIS: A prospective observational cohort study of up to 200 participants is planned, recruiting adults with primary or secondary liver cancer being considered for liver resection at Hampshire Hospitals NHS Foundation Trust. The data will be evaluated to address the primary endpoint to calculate the proportion of participants in which the results from whole genome sequencing would have resulted in a change in clinical management. Participants will be offered an additional non-invasive quantitative MRI scan prior to the operation and the impact of the imaging results on treatment decision-making will be evaluated. ETHICS AND DISSEMINATION: This study was reviewed by the NHS Health Research Authority and given favourable opinion by the Brighton and Sussex Research Ethics Committee (REC reference: 20/PR/0222). Research findings will be discussed with a patient and public involvement and engagement group, presented at relevant scientific conferences and published in open access journals. TRIAL REGISTRATION NUMBER: NCT04597710.

Quantitative magnetic resonance imaging to aid clinical decision making in autoimmune hepatitis.

Background: In autoimmune hepatitis (AIH), clinical practice and treatment guidelines frequently diverge as a reflection of disease heterogeneity and challenges in achieving standardised care. We sought to explore the utility of multiparametric (mp) MR in patients with AIH, and the impact of this technology on physicians' decision making and intended patient management. Methods: 82 AIH patients, recruited from two sites between June and November 2019 as part of an observational cohort study, underwent non-contrast MRI alongside their standard clinical investigations. Correlations between iron-corrected T1 (cT1) and other markers of disease were investigated alongside the utility of imaging markers to risk stratify patients in biochemical remission. The impact of mpMR on clinical decision making was evaluated using pairwise t-tests. The discriminatory ability of the imaging markers was assessed using area under the receiver operating characteristic curves (AUCs). Findings: cT1 had a significant impact on clinician intended patient management (p<0.0001). cT1 correlated with ALT (p = 0.0005), AST (p<0.001), IgG (p = 0.0005), and liver stiffness (p<0.0001). Patients in deep biochemical remission (N = 11; AST/ALT <50% upper limit of normal [ULN] and IgG <12 g/L) had low cT1, while 7/34 in normal biochemical remission (AST/ALT between 50 and 100% of ULN) had high cT1 and were at risk of disease flare. cT1 measures of disease heterogeneity, ALP and bilirubin made the best predictor of those not in biochemical remission (AUC:0.85). Interpretation: This study investigates the impact of mpMR results on intended clinical management in a real world setting. Findings showed that mpMR demonstrated a significant impact on clinical management of AIH and has the potential to inform patient risk stratification. Funding: This paper presents independent research supported by the Innovate UK grant (104,915).

Repeatability and reproducibility of deep-learning-based liver volume and Couinaud segment volume measurement tool.

PURPOSE: Volumetric and health assessment of the liver is crucial to avoid poor post-operative outcomes following liver resection surgery. No current methods allow for concurrent and accurate measurement of both Couinaud segmental volumes for future liver remnant estimation and liver health using non-invasive imaging. In this study, we demonstrate the accuracy and precision of segmental volume measurements using new medical software, Hepatica™. METHODS: MRI scans from 48 volunteers from three previous studies were used in this analysis. Measurements obtained from Hepatica™ were compared with OsiriX. Time required per case with each software was also compared. The performance of technicians and experienced radiologists as well as the repeatability and reproducibility were compared using Bland-Altman plots and limits of agreement. RESULTS: High levels of agreement and lower inter-operator variability for liver volume measurements were shown between Hepatica™ and existing methods for liver volumetry (mean Dice score 0.947 ± 0.010). A high consistency between technicians and experienced radiologists using the device for volumetry was shown (± 3.5% of total liver volume) as well as low inter-observer and intra-observer variability. Tight limits of agreement were shown between repeated Couinaud segment volume (+ 3.4% of whole liver), segmental liver fibroinflammation and segmental liver fat measurements in the same participant on the same scanner and between different scanners. An underestimation of whole-liver volume was observed between three non-reference scanners. CONCLUSION: Hepatica™ produces accurate and precise whole-liver and Couinaud segment volume and liver tissue characteristic measurements. Measurements are consistent between trained technicians and experienced radiologists.

Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. NAFLD is associated with excess risk of all-cause mortality, and its progression to nonalcoholic steatohepatitis (NASH) and fibrosis accounts for a growing proportion of cirrhosis and hepatocellular cancer and thus is a leading cause of liver transplant worldwide. Noninvasive precise methods to identify patients with NASH and NASH with significant disease activity and fibrosis are crucial when the disease is still modifiable. The aim of this study was to examine the clinical utility of corrected T1 (cT1) vs magnetic resonance imaging (MRI) liver fat for identification of NASH participants with nonalcoholic fatty liver disease activity score ≥4 and fibrosis stage (F) ≥2 (high-risk NASH). METHODS: Data from five clinical studies (n = 543) with participants suspected of NAFLD were pooled or used for individual participant data meta-analysis. The diagnostic accuracy of the MRI biomarkers to stratify NASH patients was determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: A stepwise increase in cT1 and MRI liver fat with increased NAFLD severity was shown, and cT1 was significantly higher in participants with high-risk NASH. The diagnostic accuracy (AUROC) of cT1 to identify patients with NASH was 0.78 (95% CI, 0.74-0.82), for liver fat was 0.78 (95% CI, 0.73-0.82), and when combined with MRI liver fat was 0.82 (95% CI, 0.78-0.85). The diagnostic accuracy of cT1 to identify patients with high-risk NASH was good (AUROC = 0.78; 95% CI, 0.74-0.82), was superior to MRI liver fat (AUROC = 0.69; 95% CI, 0.64-0.74), and was not substantially improved by combining it with MRI liver fat (AUROC = 0.79; 95% CI, 0.75-0.83). The meta-analysis showed similar performance to the pooled analysis for these biomarkers. CONCLUSIONS: This study shows that quantitative MRI-derived biomarkers cT1 and liver fat are suitable for identifying patients with NASH, and cT1 is a better noninvasive technology than liver fat to identify NASH patients at greatest risk of disease progression. Therefore, MRI cT1 and liver fat have important clinical utility to help guide the appropriate use of interventions in NAFLD and NASH clinical care pathways.

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.

Quantitative multiparametric MRI allows safe surgical planning in patients undergoing liver resection for colorectal liver metastases: report of two patients.

It is not uncommon for clinicians to encounter varying degrees of hepatic steatosis in patients undergoing resection for colorectal liver metastases (CRLM). Magnetic resonance imaging is currently the preferred investigation for identification and pre-operative planning of these patients. An objective assessment of liver quality and degree of steatosis is paramount for planning a safe resection, which is seldom provided by routine MRI sequences. We studied two patients who underwent an additional pre-operative multiparametric MRI scan (LiverMultiScanTM) as a part of an observational clinical trial (HepaT1ca, NCT03213314) to assess the quality of liver. Outcome was assessed in the form of post-hepatectomy liver failure. Both patients (Patient 1 and 2) had comparable pre-operative characteristics. Both patients were planned for an extended right hepatectomy with an estimated future liver remnant of approximately 30%. Conventional preoperative contrast MRI showed mild liver steatosis in both patients. Patient one developed post-hepatectomy liver failure leading to prolonged hospital stay compared to patient two who had uneventful post-operative course. Retrospective evaluation of multiparametric MRI scan revealed findings consistent with fibro-inflammatory disease and steatosis (cT1 829 ms, PDFF 14%) for patient 1 whereas patient two had normal parameters (cT1 735 ms, PDFF 2.4%). These findings corresponded with the resection specimen histology. Multiparametric MRI can objectively evaluate future liver health and volume which may help refine surgical decision-making and improve patient outcomes.

Multiparametric Magnetic Resonance Imaging, Autoimmune Hepatitis, and Prediction of Disease Activity.

Noninvasive monitoring of disease activity in autoimmune hepatitis (AIH) has potential advantages for patients for whom liver biopsy is invasive and with risk. We sought to understand the association of multiparametric magnetic resonance imaging (mpMRI) with clinical course of patients with AIH. We prospectively recruited 62 patients (median age, 55 years; 82% women) with clinically confirmed AIH. At recruitment, patients underwent mpMRI with LiverMultiScan alongside clinical investigations, which were repeated after 12-18 months. Associations between iron-corrected T1 (cT1) and other markers of disease were investigated at baseline and at follow-up. Discriminative performance of cT1, liver stiffness, and enhanced liver fibrosis (ELF) to identify those who failed to maintain remission over follow-up was investigated using the areas under the receiver operating characteristic curves (AUCs). Baseline cT1 correlated with alanine aminotransferase (Spearman's correlation coefficient [r S] = 0.28, P = 0.028), aspartate aminotransferase (r S = 0.26, P = 0.038), international normalized ratio (r S = 0.35 P = 0.005), Model for End-Stage Liver Disease (r S = 0.32, P = 0.020), ELF (r S = 0.29, P = 0.022), and liver stiffness r S = 0.51, P < 0.001). After excluding those not in remission at baseline (n = 12), 32% of the remainder failed to maintain remission during follow-up. Failure to maintain remission was associated with significant increases in cT1 over follow-up (AUC, 0.71; 95% confidence interval [CI], 0.52-0.90; P = 0.035) but not with changes in liver stiffness (AUC, 0.68; 95% CI, 0.49-0.87; P = 0.067) or ELF (AUC, 0.57; 95% CI, 0.37-0.78; P = 0.502). cT1 measured at baseline was a significant predictor of future loss of biochemical remission (AUC, 0.68; 95% CI, 0.53-0.83; P = 0.042); neither liver stiffness (AUC, 0.53; 95% CI, 0.34-0.71; P = 0.749) nor ELF (AUC, 0.52; 95% CI, 0.33-0.70; P = 0.843) were significant predictors of loss of biochemical remission. Conclusion: Noninvasive mpMRI has potential to contribute to risk stratification in patients with AIH.

Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort.

BACKGROUND: Non-invasive assessment of non-alcoholic steatohepatitis (NASH) is increasing in desirability due to the invasive nature and costs associated with the current form of assessment; liver biopsy. Quantitative multiparametric magnetic resonance imaging (mpMRI) to measure liver fat (proton density fat fraction) and fibroinflammatory disease [iron-corrected T1 (cT1)], as well as elastography techniques [vibration-controlled transient elastography (VCTE) liver stiffness measure], magnetic resonance elastography (MRE) and 2D Shear-Wave elastography (SWE) to measure stiffness and fat (controlled attenuated parameter, CAP) are emerging alternatives which could be utilised as safe surrogates to liver biopsy. AIM: To evaluate the agreement of non-invasive imaging modalities with liver biopsy, and their subsequent diagnostic accuracy for identifying NASH patients. METHODS: From January 2019 to February 2020, Japanese patients suspected of NASH were recruited onto a prospective, observational study and were screened using non-invasive imaging techniques; mpMRI with LiverMultiScan ®, VCTE, MRE and 2D-SWE. Patients were subsequently biopsied, and samples were scored by three independent pathologists. The diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve (AUC) with the median of the histology scores as the gold standard diagnoses. Concordance between all three independent pathologists was further explored using Krippendorff's alpha (a) from weighted kappa statistics. RESULTS: N = 145 patients with mean age of 60 (SD: 13 years.), 39% females, and 40% with body mass index ≥ 30 kg/m2 were included in the analysis. For identifying patients with NASH, MR liver fat and cT1 were the strongest performing individual measures (AUC: 0.80 and 0.75 respectively), and the mpMRI metrics combined (cT1 and MR liver fat) were the overall best non-invasive test (AUC: 0.83). For identifying fibrosis ≥ 1, MRE performed best (AUC: 0.97), compared to VCTE-liver stiffness measure (AUC: 0.94) and 2D-SWE (AUC: 0.94). For assessment of steatosis ≥ 1, MR liver fat was the best performing non-invasive test (AUC: 0.92), compared to controlled attenuated parameter (AUC: 0.75). Assessment of the agreement between pathologists showed that concordance was best for steatosis (a = 0.58), moderate for ballooning (a = 0.40) and fibrosis (a = 0.40), and worst for lobular inflammation (a = 0.11). CONCLUSION: Quantitative mpMRI is an effective alternative to liver biopsy for diagnosing NASH and non-alcoholic fatty liver, and thus may offer clinical utility in patient management.

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.

rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.

BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. METHODS: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], pz = 4.8×10-5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5×10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. CONCLUSIONS: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. LAY SUMMARY: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.

Quantitative magnetic resonance imaging predicts individual future liver performance after liver resection for cancer.

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

BACKGROUND: The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies. OBJECTIVE: The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories. METHODS: RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit. RESULTS: This trial is currently open for recruitment. The anticipated completion date for the study is December 2020. CONCLUSIONS: This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19189.

A composite biomarker using multiparametric magnetic resonance imaging and blood analytes accurately identifies patients with non-alcoholic steatohepatitis and significant fibrosis.

Non-alcoholic steatohepatitis (NASH) is major health burden lacking effective pharmacological therapies. Clinical trials enrol patients with histologically-defined NAFLD (non-alcoholic fatty liver disease) activity score (NAS) ≥ 4 and Kleiner-Brunt fibrosis stage (F) ≥ 2; however, screen failure rates are often high following biopsy. This study evaluated a non-invasive MRI biomarker, iron-corrected T1 mapping (cT1), as a diagnostic pre-screening biomarker for NASH. In a retrospective analysis of 86 biopsy confirmed NAFLD patients we explored the potential of blood and imaging biomarkers, both in isolation and in combination, to discriminate those who have NAS ≥ 4 and F ≥ 2 from those without. Stepwise logistic regression was performed to select the optimal combination of biomarkers, diagnostic accuracy was determined using area under the receiver operator curve and model validated confirmed with and fivefold cross-validation. Results showed that levels of cT1, AST, GGT and fasting glucose were all good predictors of NAS ≥ 4 and F ≥ 2, and the model identified the combination of cT1-AST-fasting glucose (cTAG) as far superior to any individual biomarker (AUC 0.90 [0.84-0.97]). This highlights the potential utility of the composite cTAG score for screening patients prior to biopsy to identify those suitable for NASH clinical trial enrolment.