Histologic Variation of Grade and Stage of Non-alcoholic Fatty Liver Disease in Liver Biopsies

Janiec, Dorota J; Jacobson, Erica; Freeth, Amy; Spaulding, Laurie; Blaszyk, Hagen

doi:10.1381/0960892053723268

Cited by 106 publications

(74 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Currently, the reference standard for the diagnosis and grading of steatosis is biopsy. However, widespread use of biopsy is limited because it is expensive, invasive, and has high sampling error (13)(14)(15). Steatosis is heterogeneous, and the sampling error likely refl ects the inherent fl aw of attempting to characterize a heterogeneous disease with a sample of only 1/50 000 of the liver.…”

Section: Patientsmentioning

confidence: 99%

“…Comparison with a single targeted biopsy is unlikely to provide adequate validation because it is well known that biopsy suffers from marked sampling variability (13)(14)(15). In addition, core biopsies are used for histologic analysis, and pathologic grading of steatosis is based on the number of cells with intracellular fat rather than actual triglyceride correlation.…”

Section: Gastrointestinal Imaging: Quantifi Cation Of Hepatic Steatosismentioning

confidence: 99%

See 1 more Smart Citation

Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy

Meisamy

Hines²,

Hamilton³

et al. 2011

Radiology

349

412

View full text Add to dashboard Cite

Purpose:To prospectively compare an investigational version of a complex-based chemical shift-based fat fraction magnetic resonance (MR) imaging method with MR spectroscopy for the quantifi cation of hepatic steatosis. Materials and Methods:This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained before all studies. Fifty-fi ve patients (31 women, 24 men; age range, 24-71 years) were prospectively imaged at 1.5 T with quantitative MR imaging and single-voxel MR spectroscopy, each within a single breath hold. The effects of T2* correction, spectral modeling of fat, and magnitude fi tting for eddy current correction on fat quantifi cation with MR imaging were investigated by reconstructing fat fraction images from the same source data with different combinations of error correction. Single-voxel T2-corrected MR spectroscopy was used to measure fat fraction and served as the reference standard. All MR spectroscopy data were postprocessed at a separate institution by an MR physicist who was blinded to MR imaging results. Fat fractions measured with MR imaging and MR spectroscopy were compared statistically to determine the correlation ( r 2 ), and the slope and intercept as measures of agreement between MR imaging and MR spectroscopy fat fraction measurements, to determine whether MR imaging can help quantify fat, and examine the importance of T2* correction, spectral modeling of fat, and eddy current correction. Two-sided t tests (signifi cance level, P = .05) were used to determine whether estimated slopes and intercepts were signifi cantly different from 1.0 and 0.0 , respectively. Sensitivity and specifi city for the classifi cation of clinically signifi cant steatosis were evaluated. Results:Overall, there was excellent correlation between MR imaging and MR spectroscopy for all reconstruction combinations. However, agreement was only achieved when T2* correction, spectral modeling of fat, and magnitude fi tting for eddy current correction were used ( r 2 = 0.99; slope 6 standard deviation = 1.00 6 0.01, P = .77; intercept 6 standard deviation = 0.2% 6 0.1, P = .19 ). Conclusion:T1-independent chemical shift-based water-fat separation MR imaging methods can accurately quantify fat over the entire liver, by using MR spectroscopy as the reference standard, when T2* correction, spectral modeling of fat, and eddy current correction methods are used.q RSNA, 2011

show abstract

Section: Patientsmentioning

confidence: 99%

Section: Gastrointestinal Imaging: Quantifi Cation Of Hepatic Steatosismentioning

confidence: 99%

Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy

Meisamy

Hines²,

Hamilton³

et al. 2011

Radiology

349

412

View full text Add to dashboard Cite

show abstract

“…However, biopsy is invasive, and only a fraction of the liver is sampled (26)(27)(28)(29)(30). The histologic interpretation of biopsy results is subjective and semiquantitative ( 31-33 ).…”

Section: Study Design and Subjectsmentioning

confidence: 99%

Estimation of Hepatic Proton-Density Fat Fraction by Using MR Imaging at 3.0 T

et al. 2011

View full text Add to dashboard Cite

Purpose:To compare the accuracy of several magnetic resonance (MR) imaging-based methods for hepatic proton-density fat fraction (FF) estimation at 3.0 T, with spectroscopy as the reference technique. Materials and Methods:This prospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. One hundred sixty-three subjects (39 with known hepatic steatosis, 110 with steatosis risk factors, 14 without risk factors) underwent proton MR spectroscopy and non-T1-weighted gradient-echo MR imaging of the liver. At spectroscopy, the reference FF was determined from frequency-selective measurements of fat and water proton densities. At imaging, FF was calculated by using two-, three-, or six-echo methods, with single-frequency and multifrequency fat signal modeling. The three-and sixecho methods corrected for T2 * ; the two-echo methods did not. For each imaging method, the fat estimation accuracy was assessed by using linear regression between the imaging FF and spectroscopic FF. Binary classifi cation accuracy of imaging was assessed at four reference spectroscopic thresholds (0.04, 0.06, 0.08, and 0.10 FF). Results:Regression intercept of two-, three-, and six-echo methods were 2 0.0211, 0.0087, and 2 0.0062 ( P , .001 for all three) without multifrequency modeling and 2 0.0237 ( P , .001), 0.0022, and 2 0.0007 with multifrequency modeling, respectively. Regression slope of two-, three-, and six-echo methods were 0.8522, 0.8528, and 0.7544 ( P , .001 for all three) without multifrequency modeling and 0.9994, 0.9775, and 0.9821 with multifrequency modeling, respectively. Signifi cant deviation of intercept and slope from 0 and 1, respectively, indicated systematic error. Classification accuracy was 82.2%-90.1%, 93.9%-96.3%, and 83.4%-89.6% for two-, three-, and six-echo methods without multifrequency modeling and 88.3%-92.0%, 95.1%-96.3%, and 94.5%-96.3% with multifrequency modeling, respectively, depending on the FF threshold. T2 * -corrected (three-and six-echo) multifrequency imaging methods had the overall highest FF estimation and classifi cation accuracy. Among methods without multifrequency modeling, the T2 * -corrected threeecho method had the highest accuracy.

show abstract

“…The tissue samples fulfilled the size requirements suggested by Janiec et al: 18 adequate liver biopsy samples were defined as having a length 41.0 cm and/ or the presence of at least 10 portal tracts. The liver tissues were fixed in 10% formaldehyde, embedded in paraffin, and cut into 4-mm-thick sections.…”

Section: Histopathological Diagnosismentioning

confidence: 99%

Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver

Motoyama

Komiya

Thủy

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), a-smooth muscle actin (a-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB-and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and a-SMA, whereas myofibroblasts around the portal vein expressed a-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, a-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB-and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express a-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become a-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.

show abstract

Histologic Variation of Grade and Stage of Non-alcoholic Fatty Liver Disease in Liver Biopsies

Abstract: Liver biopsy samples taken from the right and left hepatic lobes showed similar grades of disease activity, but differed in histopathologic staging in 30% of the NAFLD patients. Obtaining an adequately sized biopsy (>1.0 cm in length with >10 portal tracts) greatly reduces sampling error.

Cited by 106 publications

References 12 publications

Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy

Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy

Estimation of Hepatic Proton-Density Fat Fraction by Using MR Imaging at 3.0 T

Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver

Contact Info

Product

Resources

About