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Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

ABSTRACT: The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m² and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

SUBMITTER: Song I

PROVIDER: S-EPMC10761858 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

Song Isabel I Thompson Elizabeth W EW Verma Anurag A MacLean Matthew T MT Duda Jeffrey J Elahi Ameena A Tran Richard R Raghupathy Pavan P Swago Sophia S Hazim Mohamad M Bhattaru Abhijit A Schneider Carolin C Vujkovic Marijana M Torigian Drew A DA Kahn Charles E CE Gee James C JC Borthakur Arijitt A Kripke Colleen M CM Carson Christopher C CC Carr Rotonya R Jehangir Qasim Q Ko Yi-An YA Litt Harold H Rosen Mark M Mankoff David A DA Schnall Mitchell D MD Shou Haochang H Chirinos Julio J Damrauer Scott M SM Serper Marina M Chen Jinbo J Rader Daniel J DJ Witschey Walter R T WRT Sagreiya Hersh H

Scientific reports 20240102 1

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantita ...[more]

PMID: 38167550

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Project description:BackgroundThe prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available.AimsAssess risk factors for liver steatosis in lean patients and investigate its impact on survival.MethodsPatients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival.ResultsAmong n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP < 268 dB/m). Patients with steatosis had higher GGT (238.0(± 450.3) vs. 112.1(± 180.0) IU/mL; p = 0.013), AST (63(± 67.4) vs. 38.5(± 32.9) IU/mL; p = 0.001), ALT (59.1(± 58.8) vs. 44.3(± 52.7) IU/mL; p = 0.048) and triglyceride levels (120.1(± 80.3) vs. 96.1(± 58.2) mg/dL; p = 0.014), and showed a trend toward more severe fibrosis (LSM 15.6(± 19.5) vs. 12.0(± 15.7) kPa; p = 0.115). In multivariate binary logistic regression analysis, only serum uric acid levels were independently associated with liver steatosis (odds ratio 1.43 per unit mg/dL; 95% CI 1.001-2.054; p = 0.049). During a mean follow-up of 38.9(± 10.6) months, n = 14 patients (5.0%) died. In the absence of advanced fibrosis, survival after 1 year was similar in patients without (98.7%) and with (98.6%) significant steatosis. Patients with advanced fibrosis had worse 1-year survival without concomitant significant steatosis (84.8%) than patients with steatosis (95.8%; log-rank p < 0.001).ConclusionsHigh serum uric acid levels increase the risk of liver steatosis in lean patients. Liver fibrosis but not hepatic steatosis is a risk factor for impaired survival in lean patients.

Project description:(1) Background: pathological changes in hepatic Langerhans cell histiocytosis (LCH) have been observed; however, corresponding imaging findings can appear vague to physicians and radiologists. The present study aimed to comprehensively illustrate the imaging findings of hepatic LCH and to investigate the evolution of LCH-associated lesions. (2) Methods: LCH patients with liver involvement treated at our institution were retrospectively reviewed along with prior studies in PubMed. Initial and follow-up computed tomography (CT) and magnetic resonance imaging (MRI) were systematically reviewed, and three imaging phenotypes were created based on the lesion distribution pattern. Clinical features and prognoses were compared among the three phenotypes. Liver fibrosis was evaluated visually on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values of the fibrotic areas were measured. Descriptive statistics and a comparative analysis were used to analyze the data. (3) Results: based on the lesion distribution pattern on CT/MRI scans, patients with liver involvement were categorized as the disseminated lesion phenotype, scattered lesion phenotype, and central periportal lesion phenotype. Patients with scattered lesion phenotype were typically adults, and only a few of them had hepatomegaly (npresent = 1, 1/6, 16.7%) and liver biochemical abnormalities (npresent = 2, 2/6, 33.3%); patients with central periportal lesion phenotype were typically young children, and hepatomegaly and biochemical abnormalities were more apparent in these patients than those with another phenotype; and those with the disseminated lesion phenotype were found in all age groups, and the lesions evolved rapidly on medical imaging. Follow-up MRI scans show more details and can better document the evolution of lesions than CT. T2-hypointense fibrotic changes, including the periportal halo sign (npresent = 2, 2/9, 22.2%), patchy liver parenchyma changes (npresent = 6, 6/9, 66.7%), and giant hepatic nodules close to the central portal vein (npresent = 1, 1/9, 11.1%), were found, while fibrotic changes were not observed in patients with the scattered lesion phenotype. The mean ADC value for the area of liver fibrosis in each patient was lower than the optimal cutoff for significant fibrosis (METAVIR Fibrosis Stage ≥ 2) in a previous study that assessed liver fibrosis in chronic viral hepatitis. (4) Conclusions: The infiltrative lesions and liver fibrosis of hepatic LCH can be well characterized on MRI scans with DWI. The evolution of these lesions was well demonstrated on follow-up MRI scans.

Project description:Imaging techniques are a potentially powerful method of identifying phenotypes that are associated with, or are indicative of, a vulnerability to developing major depressive disorder (MDD). Here we identify seven promising MDD-associated traits identified by magnetic resonance imaging (MRI) or positron emission tomography (PET). We evaluate whether these traits are state-independent, heritable endophenotypes, or state-dependent phenotypes that may be useful markers of treatment efficacy. In MDD, increased activity of the amygdala in response to negative stimuli appears to be a mood-congruent phenomenon, and is likely moderated by the 5-HT transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR). Hippocampal volume loss is characteristic of elderly or chronically-ill samples and may be impacted by the val66met brain-derived neurotrophic factor (BDNF) gene variant and the 5-HTTLPR SLC6A4 polymorphism. White matter pathology is salient in elderly MDD cohorts but is associated with cerebrovascular disease, and is unlikely to be a useful marker of a latent MDD diathesis. Increased blood flow or metabolism of the subgenual anterior cingulate cortex (sgACC), together with gray matter volume loss in this region, is a well-replicated finding in MDD. An attenuation of the usual pattern of fronto-limbic connectivity, particularly a decreased temporal correlation in amygdala-anterior cingulate cortex (ACC) activity, is another MDD-associated trait. Concerning neuroreceptor PET imaging, decreased 5-HT(1A) binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT(1A) gene (HTR1A: -1019 C/G; rs6295). Potentially indicative of inter-study variation in MDD etiology or mood state, both increased and decreased binding potential of the 5-HT transporter has been reported. Challenges facing the field include the problem of phenotypic and etiological heterogeneity, technological limitations, the confounding effects of medication, and non-disease related inter-individual variation in brain morphology and function. Further advances are likely as epigenetic, copy-number variant, gene-gene interaction, and genome-wide association (GWA) approaches are brought to bear on imaging data.

Dataset Information

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

Publications

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

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