Karaciğer Yağlanma Oranı Tespitinde Dijital Patolojinin Katkısı
Amaç: Yağlanma oranı, steatohepatit tanısında ve transplantasyon öncesiverici adayı karaciğer biyopsilerinde değerlendirilmesi gerekenparametrelerdendir. Kantitatif/semikantitatif olarak değerlendirilen yağlanmayüzdeleri, gözlemci-içi ve gözlemciler arası farklılık göstermektedir. Bu farklılığıen aza indirgemek amaçlı, görüntü analizi yöntemleri geliştirilmektedir.Çalışmamızda, karaciğer yağlanmasını taklit eden sanal olarak oluşturulmuşdijitalize resimler, patologlar tarafından incelenmiştir. Sonuçların bilgisayarcahesaplanan değerler ile uyum oranları ve klinik yönetimi etkileyecekdeğerlendirme farklılıklarına neden olup olmadığı araştırılmıştır.Yöntem: ’Kameram’ programı ile hazırlanmış, pembe zeminde, yağlanmayıtemsil eden, alan ölçüleri bilinen beyaz dairesel boşluklar içeren 9 resim,İstanbul Hepatopankreatobiliyer patoloji çalışma grubu ile paylaşıldı.Katılımcılardan her resim için yağlanma yüzdesi belirtmeleri istendi. Sonuçlar,bilgisayar tarafından hesaplanan değerler ile kıyaslandı.Bulgular: Çalışmaya 19 patolog katıldı. Onbeşi resimlerin tamamında ya daçoğunda bilgisayarın hesapladığı değerlere göre yüksek yağlanma yüzdesibelirtti. Sadece 1 katılımcı, bilgisayar ile aynı değerleri bildirdi. Bilgisayardeğerleri ile patologların değerleri arasında %40’a kadar yüksek, %20’ye kadardüşük değişkenlik mevcuttu. Resimlerin verici adayı karaciğerini temsil ettiğidüşünüldüğünde, 11 patolog 1 olguda, 4 patolog 2 olguda, 1 patolog 3 olgudaklinik yönetimi etkileyebilecek değerlendirme yaparken, 3 patolog tümolgularda klinik yönetimi etkilemeyecek değerlendirme yaptı. Resimlerinsteatohepatit değerlendirmesini temsil ettiği düşünüldüğünde, sadece 2 resimtüm patologlar tarafından bilgisayar ile aynı şekilde skorlandı ve resimlerin5’inde en az 2 patologun bilgisayar değerlerine göre yüksek skor verdiğigörüldü. Patologlar arası uyum steatohepatit ve verici karaciğerinideğerlendirmede orta-iyi düzeydeydi (sırasıyla kappa değerleri: 0.51 ve 0.63)Sonuç: Çalışmamızda, karaciğer yağlanma oranlarının patologlar tarafındangenel olarak yüksek değerlendirildiği gözlenmektedir. Steatohepatitsınıflamasında ve greft yönetimi açısından kliniği farklı etkileyen kararlarverilebileceği düşünülmüştür. Patoloji rutinine her geçen gün daha fazla dahilolan bilgisayar destekli otomatize programların, patologlar arasıdeğerlendirme farklılıkları ve klinik yansımaları nedeniyle, karaciğer yağlanmaoranlarının doğru tespitinde de yeri olabileceği görülmektedir.
Contribution of Digital Pathology on the Determination of Liver Steatosis Ratio
Objective: The rate of steatosis is the parameter that should be assessed in steatohepatitis and donor liver biopsies before transplantation. The percentage of steatosis, evaluated as quantitative / semiquantitative, differs between observers and intra-observers. Various image analysis methods have been developed in order to reduce this difference. In our study, pathologists examined virtually created digitized images mimicking liver fat. The results’ accuracy rates and differences in assessment, that would impact clinical management, were investigated. Methods: Nine pictures with white circles on a pink background, simulating steatosis, were prepared with the ‘Kameram’ program. The steatosis area was calculated by computer. These pictures were shared with the Istanbul Hepatopancreatobiliary pathology study group. Participants were asked to specify the percentage of steatosis for each image. The results were compared to computer values. Results: Nineteen pathologists participated in the evaluation. Fifteen of the pathologists indicated higher steatosis percentage than the computirised calculated values, either in all pictures or most of the pictures. Only 1 participant reported the same values with the computer. Difference between computer values and pathologists' values ranged from as high as 40% to as low as 20%. When the images were thought to represent the donor liver, only 3 pathologists succeeded in proper clinical management in all cases, while 11 of the pathologists had misdiagnosed clinical management in 1 case, 4 pathologists in 2 cases, 1 pathologist in 3 cases. When it was thought that the pictures represented the steatohepatitis evaluation, all pathologists correctly scored only 2 pictures and at least 2 pathologists gave high scores in 5 of the pictures. Inter-pathologist agreement was moderate to good with assessing steatohepatitis and donor liver (kappa values, respectively: 0.51 and 0.63). Conclusion: In our study, it is observed that pathologists generally evaluate the steatosis rate higher than real calculated values. This can affect the clinic, in both steatohepatitis scoring classification and graft management differently. Computer-aided automated programs, which are increasingly used in routine pathology to overcome the differences in pathologist evaluations and clinical manifestations, also can have a role in the detection of liver steatosis ratio.
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- Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C.
Prevalence of fatty liver in children and adolescents. Pediatrics.
2006;118:1388-93.
- Brunt EM. Pathology of nonalcoholic fatty liver disease. Nature reviews
Gastroenterology & hepatology. 2010;7(4):195-203.
- Fiorini RN, Kirtz J, Periyasamy B, Evans Z, Haines JK, Cheng G, et al.
Development of an unbiased method for the estimation of liver steatosis.
Clinical transplantation. 2004;18:700-6.
- Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et
al. Design and validation of a histological scoring system for nonalcoholic fatty
liver disease. Hepatology. 2005;41:1313-21.
- Mazhar SM, Shiehmorteza M, Sirlin CB. Noninvasive assessment of hepatic
steatosis. Clinical gastroenterology and hepatology : the official clinical
practice journal of the American Gastroenterological Association. 2009;7:135-
40.
- Gawrieh S, Knoedler DM, Saeian K, Wallace JR, Komorowski RA. Effects of
interventions on intra- and interobserver agreement on interpretation of
nonalcoholic fatty liver disease histology. Annals of diagnostic pathology.
2011;15:19-24.
- Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al.
Sampling variability of liver biopsy in nonalcoholic fatty liver disease.
Gastroenterology. 2005;128:1898-906.
- Vuppalanchi R, Unalp A, Van Natta ML, Cummings OW, Sandrasegaran KE,
Hameed T, et al. Effects of liver biopsy sample length and number of readings
on sampling variability in nonalcoholic Fatty liver disease. Clinical
gastroenterology and hepatology : the official clinical practice journal of the
American Gastroenterological Association. 2009;7:481-6.
- Vanderbeck S, Bockhorst J, Komorowski R, Kleiner DE, Gawrieh S. Automatic
classification of white regions in liver biopsies by supervised machine learning.
Human pathology. 2014;45:785-92.
- Turlin B, Ramm GA, Purdie DM, Laine F, Perrin M, Deugnier Y, et al.
Assessment of hepatic steatosis: comparison of quantitative and
semiquantitative methods in 108 liver biopsies. Liver international : official
journal of the International Association for the Study of the Liver. 2009;29530-
5.
- Boyles TH, Johnson S, Garrahan N, Freedman AR, Williams GT. A validated
method for quantifying macrovesicular hepatic steatosis in chronic hepatitis
C. Analytical and quantitative cytology and histology. 2007;29:244-50.
- Franzen LE, Ekstedt M, Kechagias S, Bodin L. Semiquantitative evaluation
overestimates the degree of steatosis in liver biopsies: a comparison to
stereological point counting. Modern pathology : an official journal of the
United States and Canadian Academy of Pathology, Inc. 2005;18:912-6.
- Marsman H, Matsushita T, Dierkhising R, Kremers W, Rosen C, Burgart L, et
al. Assessment of donor liver steatosis: pathologist or automated software?
Human pathology. 2004;35:430-5.
- Liquori GE, Calamita G, Cascella D, Mastrodonato M, Portincasa P, Ferri D.
An innovative methodology for the automated morphometric and
quantitative estimation of liver steatosis. Histology and histopathology.
2009;24:49-60.
- D'Alessandro AM, Kalayoglu M, Sollinger HW, Hoffmann RM, Reed A,
Knechtle SJ, et al. The predictive value of donor liver biopsies on the
development of primary nonfunction after orthotopic liver transplantation.
Transplantation proceedings. 1991;23:1536-7.
- Vanderbeck S, Bockhorst J, Kleiner D, Komorowski R, Chalasani N, Gawrieh
S. Automatic quantification of lobular inflammation and hepatocyte
ballooning in nonalcoholic fatty liver disease liver biopsies. Human pathology.
2015;46:767-75.
- El-Badry AM, Breitenstein S, Jochum W, Washington K, Paradis V, RubbiaBrandt
L, et al. Assessment of hepatic steatosis by expert pathologists: the end
of a gold standard. Annals of surgery. 2009;250:691-7.
- Bedossa P, Poynard T, Naveau S, Martin ED, Agostini H, Chaput JC. Observer
variation in assessment of liver biopsies of alcoholic patients. Alcoholism,
clinical and experimental research. 1988;12:173-8.
- Auger J, Schoevaert D, Martin ED. Comparative study of automated
morphometric and semiquantitative estimations of alcoholic liver steatosis.
Analytical and quantitative cytology and histology. 1986;8:56-62.
- Hall AR, Green AC, Luong TV, Burroughs AK, Wyatt J, Dhillon AP. The use of
guideline images to improve histological estimation of hepatic steatosis. Liver
international : official journal of the International Association for the Study of
the Liver. 2014;34:1414-27.
- Hall AR, Dhillon AP, Green AC, Ferrell L, Crawford JM, Alves V, et al. Hepatic
steatosis estimated microscopically versus digital image analysis. Liver
international : official journal of the International Association for the Study of
the Liver. 2013;33:926-35.
- Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver
fibrosis in patients with nonalcoholic steatohepatitis. Hepatology.
1999;30:1356-62.
- Levene AP, Kudo H, Armstrong MJ, Thursz MR, Gedroyc WM, Anstee QM,
et al. Quantifying hepatic steatosis - more than meets the eye. Histopathology.
2012;60:971-81.
- Nativ NI, Chen AI, Yarmush G, Henry SD, Lefkowitch JH, Klein KM, et al.
Automated image analysis method for detecting and quantifying
macrovesicular steatosis in hematoxylin and eosin-stained histology images of
human livers. Liver transplantation : official publication of the American
Association for the Study of Liver Diseases and the International Liver
Transplantation Society. 2014;20:228-36.
- Younossi ZM, Gramlich T, Liu YC, Matteoni C, Petrelli M, Goldblum J, et al.
Nonalcoholic fatty liver disease: assessment of variability in pathologic
interpretations. Modern pathology : an official journal of the United States
and Canadian Academy of Pathology, Inc. 1998;11:560-5.