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Histologic scoring systems for chronic liver disease

Maria Isabel Fiel, MD, FAASLD
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Histologic scoring systems for chronic liver disease are used to characterize and predict disease progression, to determine prognosis, to guide treatment strategies, and to provide standards in clinical trials.

This topic will review the major histologic scoring systems for chronic liver disease. The interpretation of liver biopsy specimens in general and methods to obtain liver biopsy specimens are discussed elsewhere. (See "Interpretation of liver biopsy specimens" and "Approach to liver biopsy" and "Transjugular liver biopsy".)


There are several limitations of liver biopsy for assessing liver disease, including:

Variable quality of liver biopsy specimens – Specimens shorter than 2 cm in length may be difficult to interpret. Larger caliber needles may yield better samples than fine needle biopsies [1,2]. As an example, small specimens may underestimate the degree of inflammatory activity and fibrosis in patients with viral hepatitis [3].

Sampling variability – The assessment of liver histology is usually based on a percutaneous biopsy that samples a very small portion (1/50,000th) of the liver [4]. Liver disease does not always affect the liver in a homogeneous pattern, leading to the possibility of sampling variability. The most common setting for sampling error is in a cirrhotic liver [4].

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Literature review current through: Nov 2017. | This topic last updated: Jul 19, 2017.
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  1. Colloredo G, Guido M, Sonzogni A, Leandro G. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 2003; 39:239.
  2. Schiano TD, Azeem S, Bodian CA, et al. Importance of specimen size in accurate needle liver biopsy evaluation of patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2005; 3:930.
  3. Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003; 38:1449.
  4. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 2014; 20:475.
  5. Rousselet MC, Michalak S, Dupré F, et al. Sources of variability in histological scoring of chronic viral hepatitis. Hepatology 2005; 41:257.
  6. Soloway RD, Baggenstoss AH, Schoenfield LJ, Summerskill WH. Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy. Am J Dig Dis 1971; 16:1082.
  7. Goldin RD, Goldin JG, Burt AD, et al. Intra-observer and inter-observer variation in the histopathological assessment of chronic viral hepatitis. J Hepatol 1996; 25:649.
  8. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1:431.
  9. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. Hepatology 1994; 20:15.
  10. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24:289.
  11. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22:696.
  12. Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991; 13:372.
  13. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995; 19:1409.
  14. Fiel MI. Pathology of chronic hepatitis B and chronic hepatitis C. Clin Liver Dis 2010; 14:555.
  15. De Groote J, Desmet VJ, Gedigk P, et al. A classification of chronic hepatitis. Lancet 1968; 2:626.
  16. Bach N, Thung SN, Schaffner F. The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 1992; 15:572.
  17. Kutami R, Girgrah N, Wanless I, et al. The Laennec grading system for assessment of hepatic fibrosis: validation by correlation with wedged hepatic vein pressure and clinical features. Hepatology 2000; 32:407A.
  18. Rastogi A, Maiwall R, Bihari C, et al. Cirrhosis histology and Laennec staging system correlate with high portal pressure. Histopathology 2013; 62:731.
  19. Kim SU, Oh HJ, Wanless IR, et al. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol 2012; 57:556.
  20. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41:1313.
  21. Brunt EM, Kleiner DE, Wilson LA, et al. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 2011; 53:810.
  22. Bedossa P, Poitou C, Veyrie N, et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology 2012; 56:1751.
  23. Bedossa P, FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 2014; 60:565.
  24. Elphick DA, Dube AK, McFarlane E, et al. Spectrum of liver histology in presumed decompensated alcoholic liver disease. Am J Gastroenterol 2007; 102:780.
  25. Altamirano J, Miquel R, Katoonizadeh A, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014; 146:1231.
  26. Scheuer P. Primary biliary cirrhosis. Proc R Soc Med 1967; 60:1257.
  27. Ludwig J, Dickson ER, McDonald GS. Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol 1978; 379:103.
  28. Scheuer PJ. Ludwig Symposium on biliary disorders--part II. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis. Mayo Clin Proc 1998; 73:179.
  29. Nakanuma Y, Zen Y, Harada K, et al. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol Int 2010; 60:167.
  30. de Vries EM, de Krijger M, Färkkilä M, et al. Validation of the prognostic value of histologic scoring systems in primary sclerosing cholangitis: An international cohort study. Hepatology 2017; 65:907.
  31. Harada K, Hsu M, Ikeda H, et al. Application and validation of a new histologic staging and grading system for primary biliary cirrhosis. J Clin Gastroenterol 2013; 47:174.
  32. Portmann B, Zen Y. Inflammatory disease of the bile ducts-cholangiopathies: liver biopsy challenge and clinicopathological correlation. Histopathology 2012; 60:236.
  33. Ludwig J. Surgical pathology of the syndrome of primary sclerosing cholangitis. Am J Surg Pathol 1989; 13 Suppl 1:43.
  34. Ludwig J, Barham SS, LaRusso NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology 1981; 1:632.
  35. LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL. Current concepts. Primary sclerosing cholangitis. N Engl J Med 1984; 310:899.
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