Objective Scoring of Extent of Steatosis and Fibrosis Using Computer Assisted Image Analysis System in Liver Biopsy Of Non-alcoholic steatohepatitis Patients

  • Prateek Kinra AFMC, Wanowrie, Pune
  • Prasenjit Das AIIMS, New Delhi, India
  • Rajni Yadav AIIMS, New Delhi, India
  • Saumyaranjan Mallik AIIMS, New Delhi, India
  • Shalimar . AIIMS, New Delhi, India
  • S K Acharya AIIMS, New Delhi, India
  • Guresh Kumar AIIMS, New Delhi, India
  • Maneesh Vijay K AIIMS, New Delhi, India
  • Siddhartha Datta Gupta AIIMS, New Delhi, India
Keywords: image analysis, NASH, scoring


Background: The histological grading/staging system for Non-alcoholic steatohepatitis (NASH) encompasses the following criteria: extent of steatosis, lobular-inflammation, ballooning hepatocytes and extent of fibrosis. The existing scoring system has a drawback of high subjectivity. This study was designed with aims of studying (i) Inter & intra-observer variation; (ii) Correlation of the visual grading/staging with computer assisted image-analysis technique (IA); ultrasonography grade of fatty liver and fibroscan for extent of fibrosis. Methods:48 known cases of NASH were studied. The Sirius-red stained slides were assessed for % area of steatosis, fibrosis and parenchyma using Image Pro Plus® 6.1 image-analysis software. Results: The Kappa coefficient value for inter-observer variation was 0.338 (SE: 0.111-fair agreement); intra-observer variation was -0.083 (SE: 0.143-poor agreement). There was no agreement between the steatosis scoring between visual grading and IA score (K= -0.16). IA score unlike visual score correlated well with the USG grading system (K= 0.65) and biochemical variables [P values TG (0.04), BMI (0.039)]. For the first time in literature image analysis fibrosis score has been assessed in cases of NASH. The correlation between fibroscan score and IA fibrosis showed good correlation (r=0.766). The paper also lays down the cut off values of %fibrosis score on image analysis. A linear progression curve has been plotted to estimate extent of actual fibrosis in liver as against the existing fibroscan test. Conclusion: Visual assessment over-estimates the area of steatosis, resulting in false higher NASH histological grade, unlike the image-analysis system. The image-analysis adds objectivity to score steatosis and fibrosis.

Author Biographies

Prateek Kinra, AFMC, Wanowrie, Pune
MD (Path), DNB (Path), MNAMS, WHO Fellow (Mol Path), Trained in Gastrointestinal Pathology Professor
Prasenjit Das, AIIMS, New Delhi, India
Dept of Path, AIIMS, New Delhi, India
Rajni Yadav, AIIMS, New Delhi, India
Dept of Path, AIIMS, New Delhi, India
Saumyaranjan Mallik, AIIMS, New Delhi, India
Dept of Pathology
Shalimar ., AIIMS, New Delhi, India
Dept of Gastroenterology
S K Acharya, AIIMS, New Delhi, India
Dept of Gastroenterology
Guresh Kumar, AIIMS, New Delhi, India
Dept of Biostatistics
Maneesh Vijay K, AIIMS, New Delhi, India
Dept of Path
Siddhartha Datta Gupta, AIIMS, New Delhi, India
Dept of Pathology


1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434-8.
2. LaBrecque DR, Abbas Z, Anania F, Ferenci P, Khan AG, Goh KL et al; World Gastroenterology Organisation. World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014 Jul;48(6):467-73.
3. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999 Jun;116(6):1413-9.
4. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74.
5. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21.
6. Juluri R, Vuppalanchi R, Olson J, Unalp A, Van Natta ML, Cummings OW et al. Generalizability of the nonalcoholic steatohepatitis Clinical Research Network histologic scoring system for nonalcoholic fatty liver disease. J Clin Gastroenterol. 2011 Jan;45(1):55-8.
7. Obika M, Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754.
8. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis Aliment Pharmacol Ther. Mar 2011; 33(5): 525–40.
9. Gurcan MN, Boucheron LE, Can A, Madabhushi A, Rajpoot NM, Yener B. Histopathological image analysis: a review. IEEE Rev Biomed Eng. 2009; 2:147-71.
10. Hübscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathology. 2006 Nov;49(5):450-65.
11. Gwet KL. Computing inter-rater reliability and its variance in the presence of high agreement. Br J Math Stat Psychol. 2008 May;61(Pt 1):29-48.
12. Li M, Song J, Liu W. Comparing Morphometric, Biochemical and Visual Measurements of Macrovesicular Steatosis of Liver. Hum Pathol. Mar 2011; 42(3): 356–60.
13. Yoneda M, Fujita K, Hiraishi H. Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD). Gut. Sep 2007; 56(9): 1330–1.
Original Article