Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: The Cross-Cohort Collaboration - PubMed (original) (raw)

Meta-Analysis

doi: 10.1111/ene.16048. Epub 2023 Aug 28.

Adrienne O'Donnell 2 3, Stefan Frenzel 4, Tian Xiao 5, Amber Yaqub 5, Pinar Yilmaz 6, Robert J de Knegt 7, Gladys E Maestre 8 9, Debora Melo van Lent 3 10 11, Michelle Long 12, Monica Gireud-Goss 10, Till Ittermann 13, Fabian Frost 14, Robin Bülow 15, Ramachandran S Vasan 3 16 17, Hans J Grabe 4 18, M Arfan Ikram 5 6, Alexa S Beiser 2 3 17, Sudha Seshadri 3 10 11

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Meta-Analysis

Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: The Cross-Cohort Collaboration

Galit Weinstein et al. Eur J Neurol. 2024 Jan.

Abstract

Background and purpose: Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults.

Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and RS. Linear regression models were used to explore the relation of NAFLD and liver fibrosis with brain volumes, including total brain, gray matter, hippocampus, and white matter hyperintensities, adjusting for potential confounders. Results were combined using fixed effects meta-analysis.

Results: In total, 5660 and 3022 individuals were included for NAFLD and liver fibrosis analyses, respectively. NAFLD was associated with smaller volumes of total brain (β = -3.5, 95% confidence interval [CI] = -5.4 to -1.7), total gray matter (β = -1.9, 95% CI = -3.4 to -0.3), and total cortical gray matter (β = -1.9, 95% CI = -3.7 to -0.01). In addition, liver fibrosis (defined as liver stiffness measure ≥8.2 kPa) was related to smaller total brain volumes (β = -7.3, 95% CI = -11.1 to -3.5). Heterogeneity between studies was low.

Conclusions: NAFLD and liver fibrosis may be directly related to brain aging. Larger and prospective studies are warranted to validate these findings and identify liver-related preventive strategies for neurodegeneration.

Keywords: brain MRI; brain aging; liver fibrosis; nonalcoholic fatty liver disease; observational study.

© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Conflict of interest statement

H.J.G. has received travel grants and speaker honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care. None of the other authors has any conflict of interest to disclose.

Figures

FIGURE 1

FIGURE 1

Forest plots of the associations between nonalcoholic fatty liver disease (NAFLD) and total brain volume (a), total gray matter volume (b), total cortical gray matter volume (c), hippocampal volume (d), and white matter hyperintensity volume (e). Cohort‐specific effect sizes (red squares) represent mean differences of each brain magnetic resonance imaging (MRI) outcome comparing clinically significant liver fibrosis to no fibrosis. Horizontal lines extending from squares represent 95% confidence intervals (CIs). Pooled estimates (black diamonds) were combined using fixed effects meta‐analysis. Models adjust for age, age‐squared, sex, total intracranial volume, ethnicity, time between NAFLD assessment and MRI, body fat, hypertension, and diabetes. FHS, Framingham Heart Study; IV, intravenous; RS, Rotterdam Study; SHIP, Study of Health in Pomerania.

FIGURE 2

FIGURE 2

Forest plots of the associations between liver fibrosis (liver stiffness measure ≥ 8.2 kPa) and total brain volume (a), total gray matter volume (b), total cortical gray matter volume (c), hippocampal volume (d), and white matter hyperintensity volume (e). Cohort‐specific effect sizes (red squares) represent mean differences of each brain magnetic resonance imaging (MRI) outcome comparing clinically significant liver fibrosis to no fibrosis. Horizontal lines extending from squares represent 95% confidence intervals (CI). Pooled estimates (black diamonds) were combined using fixed effects meta‐analysis. Models adjust for age, age‐squared, sex, total intracranial volume, ethnicity, time between nonalcoholic fatty liver disease assessment and MRI, body mass index, hypertension, and diabetes. FHS, Framingham Heart Study; IV, intravenous; RS, Rotterdam Study.

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