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Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

ABSTRACT: Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis.To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness.We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE.Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF ?5%) and advanced fibrosis (defined as MRE ?3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase.This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.

SUBMITTER: Doycheva I

PROVIDER: S-EPMC4673036 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

Doycheva I I Cui J J Nguyen P P Costa E A EA Hooker J J Hofflich H H Bettencourt R R Brouha S S Sirlin C B CB Loomba R R

Alimentary pharmacology & therapeutics 20150915 1

<h4>Background</h4>Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis.<h4>Aim</h4>To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic r ...[more]

PMID: 26369383

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Project description:AimsTo develop, validate and compare a non-invasive fibrosis scoring system for non-alcoholic fatty liver disease (NAFLD) derived from routinely obtained clinical and biochemical parameters.Methods267 consecutive patients with biopsy proven fatty liver or non-alcoholic steatohepatitis were randomly assigned to the estimation (2/3) or validation (1/3) group to develop a model for the prediction of advanced fibrosis. Univariate statistics were performed to compare patients with and without advanced fibrosis, and following a multivariate logistic regression analysis a new scoring system was constructed. This non-invasive Koeln-Essen-index (NIKEI) was validated and compared to the FIB-4 index by calculating the area under the receiver operating characteristic curve (AUC). We evaluated a stepwise combination of both scoring systems for the precise prediction of advanced fibrosis. To set in contrast, we additionally tested the diagnostic accuracy of the AST/ALT ratio, BARD score and the NAFLD fibrosis score in our cohort.ResultsAge, AST, AST/ALT ratio, and total bilirubin were identified as significant predictors of advanced fibrosis and used to construct the NIKEI with an AUC of 0.968 [0.937; 0.998] compared to 0.929 [0.869; 0.989] for the FIB-4 index. The absence of advanced fibrosis could be confirmed with excellent accuracy (99-100%). The positive predictive value of the FIB-4 index was higher (100% vs. 60%), however, the false negative rate was also high (33%). With a stepwise combination of both indices 82%-84% of biopsies would have been avoidable without a single misclassification. The AUROC for AST/ALT ratio, the NAFLD fibrosis score, and the BARD score were 0.81 (95% CI, 0.72-0.90), 0.96 (95% CI 0.92-0.99), and 0.67 (95% CI 0.55-0.78), respectively.ConclusionThe NIKEI can reliably exclude advanced fibrosis in subjects with NAFLD. In combination with the FIB-4 index misclassification with inadequate clinical management can be avoided while the need for liver biopsies can be reduced.

Project description:The presence of advanced fibrosis is an important measure of the severity of chronic liver disease. Prior works that have examined the gut microbiome as a novel biomarker for advanced fibrosis have only examined patients with nonalcoholic fatty liver disease. Therefore, our goal was to examine the gut microbiome across varying etiologies of liver disease to create a predictive model for liver fibrosis based upon a microbial signature. Stool samples were obtained from patients with chronic liver disease (n = 50) undergoing FibroScan (ultrasound elastography) at the VA Greater Los Angeles Healthcare System. Healthy control patients (n = 25) were also recruited as a reference population. Fecal samples underwent 16S ribosomal RNA sequencing. Using differentially abundant microbes, a random forest classifier model was created to distinguish advanced fibrosis from mild/moderate fibrosis. The findings were then validated in a separate cohort of chronic liver disease patients (n = 37). Etiologies for liver disease included non-alcoholic liver disease (58.0%), hepatitis C (26.0%), hepatitis B (10.0%), and alcohol (6.0%). Microbiome composition was distinct in liver patients with advanced fibrosis compared to those with minimal fibrosis and healthy controls (p = 0.003). In multivariate negative binomial modeling, 26 bacterial taxa were differentially abundant in patients with advanced fibrosis as compared to those with minimal/moderate fibrosis (q-value < 0.05). A random forests classifier based on these taxa had an AUROC of 0.90 to predict advanced fibrosis. Prevotella copri, which was enriched in patients with advanced fibrosis, was the most strongly predictive microbe in the classifier. The classifier had an AUROC of 0.82 for advanced fibrosis in the validation cohort and Prevotella copri remained the strongest predictive microbe for advanced fibrosis. There is a distinct microbial signature for patients with advanced fibrosis independent of liver disease etiology and other comorbidities. These results suggest that microbial profiles can be used as a non-invasive marker for advanced fibrosis and support the hypothesis that microbes and their metabolites contribute to hepatic fibrosis.

Project description:Background & aimsCurrently available non-invasive tests, including fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM by VCTE), are highly effective at excluding advanced fibrosis (AF) (F ≥3) or cirrhosis in people with non-alcoholic fatty liver disease (NAFLD), but only have moderate ability to rule-in these conditions. Our objective was to develop and validate two new scores (Agile 4 and Agile 3+) to identify cirrhosis or AF, respectively, with optimized positive predictive value and fewer indeterminate results, in individuals with NAFLD attending liver clinics.MethodsThis international study included seven adult cohorts with suspected NAFLD who underwent liver biopsy, LSM and blood sampling during routine clinical practice or screening for trials. The population was randomly divided into a training set and an internal validation set, on which the best-fitting logistic regression model was built, and performance and goodness of fit were assessed, respectively. Furthermore, both scores were externally validated on two large cohorts. Cut-offs for high sensitivity and specificity were derived in the training set to rule-out and rule-in cirrhosis or AF and then tested in the validation set and compared to FIB-4 and LSM.ResultsEach score combined LSM, AST/ALT ratio, platelets, sex and diabetes status, as well as age for Agile 3+. Calibration plots for Agile 4 and Agile 3+ indicated satisfactory to excellent goodness of fit. Agile 4 and Agile 3+ outperformed FIB-4 and LSM in terms of AUROC, percentage of patients with indeterminate results and positive predictive value to rule-in cirrhosis or AF.ConclusionsThe two novel non-invasive scores improve identification of cirrhosis or AF among individuals with NAFLD attending liver clinics and reduce the need for liver biopsy in this population.Impact and implicationsNon-invasive tests currently used to identify patients with advanced fibrosis or cirrhosis, such as fibrosis-4 index and liver stiffness measurement by vibration-controlled transient elastography, have high negative predictive values but high false positive rates, while results are indeterminate for a large number of cases. This study provides scores that will help the clinician diagnose advanced fibrosis or cirrhosis. These new easy-to-implement scores will help liver specialists to better identify (1) patients who need more intensive follow-up, (2) patients who should be referred for inclusion in therapeutic trials, and (3) which patients should be treated with pharmacological agents when effective therapies are approved.

Project description:In order to acquire consistent k-space data in MR elastography, a fixed temporal relationship between the MRI sequence and the underlying period of the wave needs to be ensured. To this end, conventional GRE-MRE enforces synchronization through repeated triggering of the transducer and forcing the sequence repetition time to be equal to an integer multiple of the wave period. For wave frequencies below 100 Hz, however, this leads to prolonged acquisition times, as the repetition time scales inversely with frequency. A previously developed multi-shot approach (eXpresso MRE) to multi-slice GRE-MRE tackles this issue by acquiring an integer number of slices per wave period, which allows acquisition to be accelerated in typical scenarios by a factor of two or three. In this work, it is demonstrated that the constraints imposed by the eXpresso scheme are overly restrictive. We propose a generalization of the sequence in three steps by incorporating sequence delays into imaging shots and allowing for interleaved wave-phase acquisition. The Ristretto scheme is compared in terms of imaging shot and total scan duration relative to eXpresso and conventional GRE-MRE and is validated in three different phantom studies. First, the agreement of measured displacement fields in different stages of the sequence generalization is shown. Second, performance is compared for 25, 36, 40, and 60 Hz actuation frequencies. Third, the performance is assessed for the acquisition of different numbers of slices (13 to 17). In vivo feasibility is demonstrated in the liver and the breast. Here, Ristretto is compared with an optimized eXpresso sequence, leading to scan accelerations of 15% and 5%, respectively, without compromising displacement field and stiffness estimates in general. The Ristretto concept allows us to choose imaging shot durations on a fine grid independent of the number of slices and the wave frequency, permitting 2- to 4.5-fold acceleration of conventional GRE-MRE acquisitions.

Dataset Information

Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

Publications

Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

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