Dataset Information

The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.

ABSTRACT:

Background

Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.

Aim

To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.

Methods

This is a cross-sectional analysis derived from a well-characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE.

Results

Two hundred sixty-four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1-8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2-18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19-0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype-age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a -0.41 kPa (95% CI: -0.76 to -0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis.

Conclusion

Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non-invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.

SUBMITTER: Ajmera V

PROVIDER: S-EPMC8985656 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.

Ajmera Veeral V Liu Amy A Bettencourt Ricki R Dhar Debanjan D Richards Lisa L Loomba Rohit R

Alimentary pharmacology & therapeutics 20210511 1

<h4>Background</h4>Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.<h4>Aim</h4>To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.<h4>Methods</h4>This is a cross-sectional analysis deriv ...[more]

PMID: 33975381

Similar Datasets

Project description:UnlabelledRetrospective studies have shown that two-dimensional magnetic resonance elastography (2D-MRE), a novel MR method for assessment of liver stiffness, correlates with advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Prospective data on diagnostic accuracy of 2D-MRE in the detection of advanced fibrosis in NAFLD are needed. The aim of this study is to prospectively assess the diagnostic accuracy of 2D-MRE, a noninvasive imaging biomarker, in predicting advanced fibrosis (stage 3 or 4) in well-characterized patients with biopsy-proven NAFLD. This is a cross-sectional analysis of a prospective study including 117 consecutive patients (56% women) with biopsy-proven NAFLD who underwent a standardized research visit: history, exam, liver biopsy assessment (using the nonalcoholic steatohepatitis Clinical Research Network histological scoring system), and 2D-MRE from 2011 to 2013. The radiologist and pathologist were blinded to clinical and pathology/imaging data, respectively. Receiver operating characteristics (ROCs) were examined to assess the diagnostic test performance of 2D-MRE in predicting advanced fibrosis. The mean (± standard deviation) of age and body mass index was 50.1 (± 13.4) years and 32.4 (± 5.0) kg/m(2), respectively. The median time interval between biopsy and 2D-MRE was 45 days (interquartile range: 50 days). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 43, 39, 13, 12, and 10, respectively. The area under the ROC curve for 2D-MRE discriminating advanced fibrosis (stage 3-4) from stage 0-2 fibrosis was 0.924 (P < 0.0001). A threshold of >3.63 kPa had a sensitivity of 0.86 (95% confidence interval [CI]: 0.65-0.97), specificity of 0.91 (95% CI: 0.83-0.96), positive predictive value of 0.68 (95% CI: 0.48-0.84), and negative predictive value of 0.97 (95% CI: 0.91-0.99).ConclusionsMRE is accurate in predicting advanced fibrosis and may be utilized for noninvasive diagnosis of advanced fibrosis in patients with NAFLD.

Project description:Background and aimsCross-sectional studies have shown that magnetic resonance elastography (MRE) is accurate in the noninvasive detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD). However, there are limited data on the longitudinal association between an increase in liver stiffness on MRE and fibrosis progression in NAFLD. Therefore, using a well-characterized prospective cohort of patients with biopsy-proven NAFLD, we aimed to examine the longitudinal association between a 15% increase in liver stiffness on MRE and fibrosis progression in NAFLD.Approach and resultsThis prospective cohort study included 102 patients (62.7% women) with biopsy-proven NAFLD who underwent contemporaneous MRE and liver biopsy at baseline followed by a repeat paired liver biopsy and MRE assessment. The primary outcome was odds of fibrosis progression by one or more stage as assessed by the Nonalcoholic Steatohepatitis Clinical Research Network histologic scoring system. The mean (±SD) of age and body mass index (BMI) were 52 (±14) years and 32.6 (±5.3) kg/m2 , respectively. The median time interval between the two paired assessments was 1.4 years (interquartile range 2.15 years). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 27, 36, 12, 17, and 10, respectively. In unadjusted analysis, a 15% increase in MRE was associated with increased odds of histologic fibrosis progression (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.17-10.76; P = 0.0248). These findings remained clinically and statistically significant even after multivariable adjustment for age, sex, and BMI (adjusted OR, 3.36; 95% CI, 1.10-10.31; P = 0.0339). A 15% increase in MRE was the strongest predictor of progression to advanced fibrosis (OR, 4.90; 95% CI, 1.35-17.84; P = 0.0159).ConclusionsA 15% increase in liver stiffness on MRE may be associated with histologic fibrosis progression and progression from early fibrosis to advanced fibrosis.

Project description:BACKGROUND:A recent retrospective study confirmed that hepatic stiffness and splenic stiffness measured with magnetic resonance elastography (MRE) are strongly associated with the presence of esophageal varices. In addition, strong correlations have been reported between splenic stiffness values measured with MRE and hepatic venous pressure gradients in animal models. However, most studies have been conducted on adult populations, and previous pediatric MRE studies have only demonstrated the feasibility of MRE in pediatric populations, while the actual clinical application of spleen MRE has been limited. AIM:To assess the utility of splenic stiffness measurements by MRE to predict gastroesophageal varices in children. METHODS:We retrospectively reviewed abdominal MRE images taken on a 3T system in pediatric patients. Patients who had undergone Kasai operations for biliary atresia were selected for the Kasai group, and patients with normal livers and spleens were selected for the control group. Two-dimensional spin-echo echo-planar MRE acquisition centered on the liver, with a pneumatic driver at 60 Hz and a low amplitude, was performed to obtain hepatic and splenic stiffness values. Laboratory results for aspartate aminotransferase to platelet ratio index (APRI) were evaluated within six months of MRE, and the normalized spleen size ratio was determined with the upper normal size limit. All Kasai group patients underwent gastroesophageal endoscopy during routine follow-up. The Mann-Whitney U test, Kendall's tau b correlation and diagnostic performance analysis using the area under the curve (AUC) were performed for statistical analysis. RESULTS:The median spleen MRE value was 5.5 kPa in the control group (n = 9, age 9-18 years, range 4.7-6.4 kPa) and 8.6 kPa in the Kasai group (n = 22, age 4-18 years, range 5.0-17.8 kPa). In the Kasai group, the APRI, spleen size ratio and spleen MRE values were higher in patients with portal hypertension (n = 11) than in patients without (n = 11) (all P < 0.001) and in patients with gastroesophageal varices (n = 6) than in patients without (n = 16) (all P < 0.05), even though their liver MRE values were not different. The APRI (? = 0.477, P = 0.007), spleen size ratio (? = 0.401, P = 0.024) and spleen MRE values (? = 0.426, P = 0.016) also correlated with varices grades. The AUC in predicting gastroesophageal varices was 0.844 at a cut-off of 0.65 (100% sensitivity and 75% specificity) for the APRI, and 0.844 at a cut-off of 9.9 kPa (83.3% sensitivity and 81.3% specificity) for spleen MRE values. CONCLUSION:At a cut-off of 9.9 kPa, spleen MRE values predicted gastroesophageal varices as well as the APRI and spleen size ratio in biliary atresia patients after the Kasai operation. However, liver MRE values were not useful for this purpose.

Dataset Information

The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.

Background

Aim

Methods

Results

Conclusion

Publications

The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets