Nonalcoholic Fatty Liver Disease: Different Classifications Concordance and Relationship between Degrees of Morphological Features and Spectrum of the Disease
The morphological features of nonalcoholic fatty liver disease (NAFLD) range from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Liver biopsy remains the main tool for NASH diagnosis and many histological systems to diagnose and grade NAFLD were proposed. We evaluated the relationship among NAFLD activity score (NAS), histological diagnoses (non-NASH, possible NASH, and definite NASH), and histological algorithm proposed by Bedossa et al.; additionally the degrees of morphological features were semiquantified and correlated with non-NASH and NASH. Seventy-one liver biopsies were studied. The agreement among the three systems considering NASH and non-NASH was excellent (). Among the 22 biopsies with NAS 3-4, 72.7% showed to be NASH according to Bedossa’s algorithm. The degree of steatosis, ballooning, lobular inflammation, and fibrosis stage were correlated with NASH (). Fibrosis stage 1 was also found in non-NASH. Over the spectrum of NAFLD, no association was observed between intensity of steatosis and fibrosis grade. The degrees of lobular inflammation showed association with fibrosis stage (). In conclusion, there is agreement among different NAFLD classifications and NAS？>？4 may be a better cutoff from which to consider NASH diagnosis; besides the highest degrees of steatosis, ballooning, inflammation, and fibrosis are associated with NASH. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity that could be the main cause of chronic liver disease in the coming decades [1]. It is closely associated with states of insulin resistance such as obesity, hyperlipidemia, and type II diabetes. The morphological features of NAFLD range from simple steatosis, which frequently has a benign course, to nonalcoholic steatohepatitis (NASH) with or without fibrosis that may progress to cirrhosis [2]. Although some noninvasive biomarkers have been developed to establish diagnosis and evaluate fibrosis [3–5], liver biopsy remains the main tool for confirming the NASH diagnosis and also to provide information about its prognosis. In 1980, Ludwig et al. were the first to recognize nonalcoholic steatohepatitis as a histological entity, very similar to the one already known in the liver from patients with alcohol abuse [6]. Almost two decades later, Matteoni et al. proposed a histological system for NAFLD that classified the biopsies into four subgroups based on the following features: steatosis, necroinflammatory lesions, ballooning, Mallory-Denk hyaline, and fibrosis [7]. Types 1 and 2 were histological forms of
References
[1]
B. A. Neuschwander-Tetri, “Fatty liver and the metabolic syndrome,” Current Opinion in Gastroenterology, vol. 23, no. 2, pp. 193–198, 2007.
[2]
D. G. Tiniakos, “Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: histological diagnostic criteria and scoring systems,” European Journal of Gastroenterology & Hepatology, vol. 22, no. 6, pp. 643–650, 2010.
[3]
T. Poynard, V. Ratziu, F. Charlotte, et al., “Diagnostic value of biochemical markers (Nash Test) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease,” BMC Gastroenterology, vol. 6, article 34, 2006.
[4]
P. Angulo, J. M. Hui, G. Marchesini et al., “The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD,” Hepatology, vol. 45, no. 4, pp. 846–854, 2007.
[5]
A. Wieckowska, A. J. McCullough, and A. E. Feldstein, “Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future,” Hepatology, vol. 46, no. 2, pp. 582–589, 2007.
[6]
J. Ludwig, T. R. Viggiano, D. B. McGill, and B. J. Ott, “Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease,” Mayo Clinic Proceedings, vol. 55, no. 7, pp. 434–438, 1980.
[7]
C. A. Matteoni, Z. M. Younossi, T. Gramlich, N. Boparai, and A. J. McCullough, “Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity,” Gastroenterology, vol. 116, no. 6, pp. 1413–1419, 1999.
[8]
E. M. Brunt, C. G. Janney, A. M. Di Bisceglie, B. A. Neuschwander-Tetri, and B. R. Bacon, “Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions,” The American Journal of Gastroenterology, vol. 94, no. 9, pp. 2467–2474, 1999.
[9]
D. E. Kleiner, E. M. Brunt, M. van Natta et al., “Design and validation of a histological scoring system for nonalcoholic fatty liver disease,” Hepatology, vol. 41, no. 6, pp. 1313–1321, 2005.
[10]
E. M. Brunt, D. E. Kleiner, L. A. Wilson, P. Belt, and B. A. Neuschwander-Tetri, “Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings,” Hepatology, vol. 53, no. 3, pp. 810–820, 2011.
[11]
P. Bedossa, C. Poitou, N. Veyrie et al., “Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients,” Hepatology, vol. 56, no. 5, pp. 1751–1759, 2012.
[12]
J. R. Landis and G. G. Koch, “The measurement of observer agreement for categorical data,” Biometrics, vol. 33, no. 1, pp. 159–174, 1977.
[13]
Z. M. Younossi, M. Stepanova, N. Rafiq et al., “Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality,” Hepatology, vol. 53, no. 6, pp. 1874–1882, 2011.
[14]
A. J. Sanyal, E. M. Brunt, D. E. Kleiner et al., “Endpoints and clinical trial design for nonalcoholic steatohepatitis,” Hepatology, vol. 54, no. 1, pp. 344–353, 2011.
[15]
E. M. Brunt, D. E. Kleiner, C. Behling et al., “Misuse of scoring systems,” Hepatology, vol. 54, no. 1, pp. 369–370, 2011.
[16]
D. E. Kleiner and E. M. Brunt, “Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research,” Seminars in Liver Disease, vol. 32, no. 1, pp. 3–13, 2012.
[17]
M. Hjelkrem, C. Stauch, J. Shaw, and S. Harrison, “Validation of the non-alcoholic fatty liver disease activity score,” Alimentary Pharmacology & Therapeutics, vol. 34, no. 2, pp. 214–218, 2011.
[18]
N. Chalasani, L. Wilson, D. E. Kleiner, O. W. Cummings, E. M. Brunt, and A. ünalp, “Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease,” Journal of Hepatology, vol. 48, no. 5, pp. 829–834, 2008.
[19]
O. Pournik, S. M. Alavian, L. Ghalichi, et al., “Inter-observer and intra-observer agreement in pathological evaluation of non-alcoholic fatty liver disease suspected liver biopsies,” Hepatitis Monthly, vol. 14, no. 1, Article ID e15167, 2014.
[20]
C. Lackner, M. Gogg-Kamerer, K. Zatloukal, C. Stumptner, E. M. Brunt, and H. Denk, “Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis,” Journal of Hepatology, vol. 48, no. 5, pp. 821–828, 2008.
[21]
R. Pais, F. Charlotte, L. Fedchuk et al., “A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver,” Journal of Hepatology, vol. 59, no. 3, pp. 550–556, 2013.
[22]
T. Gramlich, D. E. Kleiner, A. J. McCullough, C. A. Matteoni, N. Boparai, and Z. M. Younossi, “Pathologic features associated with fibrosis in nonalcoholic fatty liver disease,” Human Pathology, vol. 35, no. 2, pp. 196–199, 2004.
[23]
H. Fujii and N. Kawada, “Inflammation and fibrogenesis in steatohepatitis,” Journal of Gastroenterology, vol. 47, no. 3, pp. 215–225, 2012.
[24]
H. Miyaaki, T. Ichikawa, K. Nakao, et al., “Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis,” Liver International, vol. 28, no. 4, pp. 519–524, 2008.
