Subclinical liver traits are associated with structural and hemodynamic brain imaging markers

Abstract

Background & Aims: Impaired liver function affects brain health and therefore understanding potential mechanisms for subclinical liver disease is essential. We assessed the liver-brain associations using liver measures with brain imaging markers, and cognitive measures in the general population. Methods: Within the population-based Rotterdam Study, liver serum and imaging measures (ultrasound and transient elastography), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) and fibrosis phenotypes, and brain structure were determined in 3493 non-demented and strokefree participants in 2009-2014. This resulted in subgroups of n = 3493 for MAFLD (mean age 69 ± 9 years, 56% ♀), n = 2938 for NAFLD (mean age 70 ± 9 years, 56% ♀) and n = 2252 for fibrosis (mean age 65 ± 7 years, 54% ♀). Imaging markers of small vessel disease and neurodegeneration, cerebral blood flow (CBF) and brain perfusion (BP) were acquired from brain MRI (1.5-tesla). General cognitive function was assessed by Mini-Mental State Examination and the g-factor. Multiple linear and logistic regression models were used for liver-brain associations and adjusted for age, sex, intracranial volume, cardiovascular risk factors and alcohol use.Results: Higher gamma-glutamyltransferase (GGT) levels were significantly associated with smaller total brain volume (TBV, standardized mean difference (SMD), −0.02, 95% confidence interval (CI) (−0.03 to −0.01); p = 8.4•10 −4 ), grey matter volumes, and lower CBF and BP. Liver serum measures were not related to small vessel disease markers, nor to white matter microstructural integrity or general cognition.Participants with ultrasound-based liver steatosis had a higher fractional anisotropy (FA, SMD 0.11, 95% CI (0.04 to 0.17), p = 1.5•10 −3 ) and lower CBF and BP. MAFLD and NAFLD phenotypes were associated with alterations in white matter microstructural integrity (NAFLD ~ FA, SMD 0.14, 95% CI (0.

Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms

“…Others have also interestingly reported an association of NAFLD with altered executive and frontal lobe function, depressive mood, anxiety, and apathy ( Moretti et al, 2019 ). Further linking liver function and brain health, in a large population-based study of over 3,400 patients without dementia or prior stroke, NAFLD was found to be associated with alterations in white matter microstructural integrity, lower cerebral blood flow, and lower brain perfusion as evaluated using MRI ( Yilmaz et al, 2023 ). Animal studies have found similar changes to cerebral brain volume and suggest altered metabolism may be contributing to this.…”

The Augural Interplay of Myosteatosis and Gamma-Glutamyltransferase in Patients Undergoing Comprehensive Surgical Intervention for Cholangiocarcinoma

“…In the physiologically healthy populace, serum GGT is primarily liver-derived, and its levels tend to escalate in response to hepatic damage [15,16]. GGT exhibits a close a nity with systemic oxidative stress and in ammation, frequently displaying overexpression in malignant neoplasms, thereby bolstering tumor cell survival and proliferation [17]. Previous academic explorations have attested that ampli ed pre-treatment GGT levels augur adverse prognosis in patients a icted with various malignant tumors, including esophageal cancer, renal cancer, prostate cancer, and intrahepatic cholangiocarcinoma [14,18,19].…”