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Jing Guo

About Jing Guo:
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SEEK ID: https://seek.lisym.org/people/89

Location:  Germany

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LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Disorders of the liver show up through changes in blood tests. These blood tests indicate markers for events taking place in the liver. Usually studies of liver tissue cannot be performed: as liver samples would need to be obtained through a liver biopsy, and this procedure is not without risk, therefore these samples are usually unavailable. Complex metabolism models based on existing and new scientific data can simulate changes in the liver caused by disease. They often reveal unknown relationships
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Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research/the-liver-is-very-patient

Start date: 1st Jan 2016

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Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org

Start date: 1st Jan 2016

How histopathologic changes in pediatric nonalcoholic fatty liver disease influence in vivo liver stiffness.
LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Abstract (Expand)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. About 30% of patients with NAFLD progress to the more severe condition of nonalcoholic … steatohepatitis (NASH), which is typically diagnosed using liver biopsy. Liver stiffness (LS) quantified by elastography is a promising imaging marker for the noninvasive assessment of NAFLD and NASH in pediatric patients. However, the link between LS and specific histopathologic features used for clinical staging of NAFLD is not well defined. Furthermore, LS data reported in the literature can vary greatly due to the use of different measurement techniques. Uniquely, time-harmonic elastography (THE) based on ultrasound and magnetic resonance elastography (MRE) use the same mechanical stimulation, allowing us to compare LS in biopsy-proven NAFLD previously determined by THE and MRE in 67 and 50 adolescents, respectively. In the present work, we analyzed the influence of seven distinct histopathologic features on LS, including septal infiltration, bridging fibrosis, pericellular fibrosis, hepatocellular ballooning, portal inflammation, lobular inflammation, and steatosis. LS was highly correlated with periportal and lobular fibrosis as well as hepatocellular ballooning while no independent association was found for inflammation and steatosis. Based on this analysis, we propose a composite elastography score (CES) which includes the four key histopathologic features identified as mechanically relevant. Interestingly, CES-relevant histopathologic features were associated with zonal distribution patterns of pediatric NAFLD. Mechano-structural changes associated with NAFLD progression can be histopathologically staged using the CES, which is easily determined noninvasively based on LS measured by time-harmonic elastography.

Authors: C. A. Hudert, H. Tzschatzsch, B. Rudolph, C. Loddenkemper, H. G. Holzhutter, L. Kalveram, S. Wiegand, J. Braun, I. Sack, J. Guo

Date Published: 17th Jan 2021

Publication Type: Journal

Changes in Liver Mechanical Properties and Water Diffusivity During Normal Pregnancy Are Driven by Cellular Hypertrophy.
LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Abstract (Expand)

During pregnancy, the body's hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, … pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 +/- 15%, p < 0.001), (ii) increased liver stiffness (12 +/- 15%, p = 0.012), (iii) decreased viscosity (-23 +/- 14%, p < 0.001), and (iv) increased water diffusivity (12 +/- 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context.

Authors: K. Garczynska, H. Tzschatzsch, A. A. Kuhl, A. S. Morr, L. Lilaj, A. Hackel, E. Schellenberger, N. Berndt, H. G. Holzhutter, J. Braun, I. Sack, J. Guo

Date Published: 17th Dec 2020

Publication Type: Journal

rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

Abstract (Expand)

BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, … these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis. METHODS: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models. RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10(-5)) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10(-4)). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. CONCLUSION: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

Authors: K. Teo, K. W. M. Abeysekera, L. Adams, E. Aigner, Q. M. Anstee, J. M. Banales, R. Banerjee, P. Basu, T. Berg, P. Bhatnagar, S. Buch, A. Canbay, S. Caprio, A. Chatterjee, Y. D. Ida Chen, A. Chowdhury, A. K. Daly, C. Datz, D. de Gracia Hahn, J. K. DiStefano, J. Dong, A. Duret, C. Emdin, M. Fairey, G. S. Gerhard, X. Guo, J. Hampe, M. Hickman, L. Heintz, C. Hudert, H. Hunter, M. Kelly, J. Kozlitina, M. Krawczyk, F. Lammert, C. Langenberg, J. Lavine, L. Li, H. K. Lim, R. Loomba, P. K. Luukkonen, P. E. Melton, T. A. Mori, N. D. Palmer, C. A. Parisinos, S. G. Pillai, F. Qayyum, M. C. Reichert, S. Romeo, J. I. Rotter, Y. R. Im, N. Santoro, C. Schafmayer, E. K. Speliotes, S. Stender, F. Stickel, C. D. Still, P. Strnad, K. D. Taylor, A. Tybjaerg-Hansen, G. R. Umano, M. Utukuri, L. Valenti, L. E. Wagenknecht, N. J. Wareham, R. M. Watanabe, J. Wattacheril, H. Yaghootkar, H. Yki-Jarvinen, K. A. Young, J. P. Mann

Date Published: 31st Aug 2020

Publication Type: Journal

Tomoelastography Distinguishes Noninvasively between Benign and Malignant Liver Lesions.
LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Abstract (Expand)

Patients with increased liver stiffness have a higher risk of developing cancer, however, the role of fluid-solid tissue interactions and their contribution to liver tumor malignancy remains elusive. … Tomoelastography is a novel imaging method for mapping quantitatively the solid-fluid tissue properties of soft tissues in vivo. It provides high resolution and thus has clear clinical applications. In this work we used tomoelastography in 77 participants, with a total of 141 focal liver lesions of different etiologies, to investigate the contributions of tissue stiffness and fluidity to the malignancy of liver tumors. Shear-wave speed (c) as surrogate for tissue stiffness and phase-angle (phi) of the complex shear modulus reflecting tissue fluidity were abnormally high in malignant tumors and allowed them to be distinguished from nontumorous liver tissue with high accuracy [c: AUC = 0.88 with 95% confidence interval (CI) = 0.83-0.94; phi: AUC = 0.95, 95% CI = 0.92-0.98]. Benign focal nodular hyperplasia and hepatocellular adenoma could be distinguished from malignant lesions on the basis of tumor stiffness (AUC = 0.85, 95% CI = 0.72-0.98; sensitivity = 94%, 95% CI = 89-100; and specificity = 85%, 95% CI = 62-100), tumor fluidity (AUC = 0.86, 95% CI = 0.77-0.96; sensitivity = 83%, 95% CI = 72-93; and specificity = 92%, 95% CI = 77-100) and liver stiffness (AUC = 0.84, 95% CI = 0.74-0.94; sensitivity = 72%, 95% CI = 59-83; and specificity = 88%, 95% CI = 69-100), but not on the basis of liver fluidity. Together, hepatic malignancies are characterized by stiff, yet fluid tissue properties, whereas surrounding nontumorous tissue is dominated by solid properties. Tomoelastography can inform noninvasively on the malignancy of suspicious liver lesions by differentiating between benign and malignant lesions with high sensitivity based on stiffness and with high specificity based on fluidity. SIGNIFICANCE: Solid-fluid tissue properties measured by tomoelastography can distinguish malignant from benign masses with high accuracy and provide quantitative noninvasive imaging biomarkers for liver tumors.

Authors: M. Shahryari, H. Tzschatzsch, J. Guo, S. R. Marticorena Garcia, G. Boning, U. Fehrenbach, L. Stencel, P. Asbach, B. Hamm, J. A. Kas, J. Braun, T. Denecke, I. Sack

Date Published: 15th Nov 2019

Publication Type: Not specified

Multiparametric Quantitative MRI for the Detection of IgA Nephropathy Using Tomoelastography, DWI, and BOLD Imaging.
LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Abstract (Expand)

OBJECTIVES: The aim of this study was to noninvasively evaluate changes in renal stiffness, diffusion, and oxygenation in patients with chronic, advanced stage immunoglobulin A nephropathy (IgAN) by … multiparametric magnetic resonance imaging using tomoelastography, diffusion-weighted imaging (DWI), and blood oxygen level-dependent (BOLD) imaging. MATERIALS AND METHODS: In this prospective study, 32 subjects (16 patients with biopsy-proven IgAN and 16 age- and sex-matched healthy controls) underwent multifrequency magnetic resonance elastography with tomoelastography postprocessing at 4 frequencies from 40 to 70 Hz to generate shear wave speed (meter per second) maps reflecting tissue stiffness. In addition, DWI and BOLD imaging were performed to determine the apparent diffusion coefficient in square millimeter per second and T2* relaxation time in milliseconds, respectively. Regions including the entire renal parenchyma of both kidneys were analyzed. Areas under the receiver operating characteristic (AUCs) curve were calculated to test diagnostic performance. Clinical parameters such as estimated glomerular filtration rate and protein-to-creatinine ratio were determined and correlated with imaging findings. RESULTS: Success rates of tomoelastography, DWI, and BOLD imaging regarding both kidneys were 100%, 91%, and 87%, respectively. Shear wave speed was decreased in IgAN (-21%, P < 0.0001), accompanied by lower apparent diffusion coefficient values (-12%, P = 0.004). BOLD imaging was not sensitive to IgAN (P = 0.12). Tomoelastography detected IgAN with higher diagnostic accuracy than DWI (area under the curve = 0.9 vs 0.8) and positively correlated with estimated glomerular filtration rate (r = 0.66, P = 0.006). CONCLUSIONS: Chronic, advanced stage IgAN is associated with renal softening and restricted water diffusion. Tomoelastography is superior to DWI and BOLD imaging in detecting IgAN.

Authors: S. T. Lang, J. Guo, A. Bruns, M. Durr, J. Braun, B. Hamm, I. Sack, S. R. Marticorena Garcia

Date Published: 2nd Jul 2019

Publication Type: Not specified

Poster 28 : LiSyM Midterm Evaluation 2018 Sack Group (Berlin)
LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)
No description specified

Creator: Jing Guo

Submitter: Jing Guo

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