Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and being overweight is a significant risk factor. The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients. A cohort of 679 obese patients undergoing liver biopsy at the time of bariatric surgery was studied. An algorithm for segregating lesions into normal liver, NAFLD, or nonalcoholic steatohepatitis (NASH) was built based on semiquantitative evaluation of steatosis, hepatocellular ballooning, and lobular inflammation. For each case, the SAF score was created including the semiquantitative scoring of steatosis (S), activity (A), and fibrosis (F). Based on the algorithm, 230 obese patients (34%) were categorized as NASH, 291 (43%) as NAFLD without NASH, and 158 (23%) as not NAFLD. The activity score (ballooning + lobular inflammation) enabled discriminating NASH because all patients with NASH had A ≥ 2, whereas no patients with A < 2 had NASH. This score was closely correlated with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.0001, analysis of variance [ANOVA]). Comparison of transaminase levels between patients with normal liver and pure steatosis did not reveal significant differences, thus lending support to the proposal not to include steatosis in the activity score but to report it separately in the SAF score. In the validation series, the interobserver agreement for the diagnosis of NASH was excellent (κ = 0.80) between liver pathologists. There was no discrepancy between the initial diagnosis and the diagnosis proposed using the algorithm. Conclusion: We propose a simple but robust algorithm for categorizing liver lesions in NAFLD patients. Because liver lesions in obese patients may display a continuous spectrum of histologic lesions, we suggest describing liver lesions using the SAF score. (HEPATOLOGY 2012;56:1751–1759)

[1]  J. Dixon,et al.  Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. , 2001, Gastroenterology.

[2]  K. Flegal Trends in body weight and overweight in the U.S. population. , 2009, Nutrition reviews.

[3]  P. Giral,et al.  Liver fibrosis in overweight patients. , 2000, Gastroenterology.

[4]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[5]  B. Neuschwander‐Tetri,et al.  Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease , 2010, Hepatology.

[6]  S. McCall,et al.  Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis , 2007, Hepatology.

[7]  Z. Younossi,et al.  Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. , 1999, Gastroenterology.

[8]  P. Rosenthal,et al.  Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. , 2011, JAMA.

[9]  E. Vittinghoff,et al.  A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients , 2008, Hepatology.

[10]  P. Gill,et al.  Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. , 2013, Journal of hepatology.

[11]  H. Cortez‐Pinto,et al.  Hepatic histology in obese patients undergoing bariatric surgery. , 2006, Journal of hepatology.

[12]  Robert V Farese,et al.  Triglyceride accumulation protects against fatty acid-induced lipotoxicity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  O. Cummings,et al.  Misuse of scoring systems , 2011, Hepatology.

[14]  B. Neuschwander‐Tetri,et al.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. , 2010, The New England journal of medicine.

[15]  P. Giral,et al.  Long‐term efficacy of rosiglitazone in nonalcoholic steatohepatitis: Results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial , 2009, Hepatology.

[16]  P. Scheuer Assessment of liver biopsies in chronic hepatitis: how is it best done? , 2003, Journal of hepatology.

[17]  Kurt Zatloukal,et al.  Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. , 2008, Journal of Hepatology.

[18]  F. Pattou,et al.  Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. , 2009, Gastroenterology.

[19]  B. Neuschwander‐Tetri,et al.  Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings , 2011, Hepatology.

[20]  A. Feldstein,et al.  Pentoxifylline improves nonalcoholic steatohepatitis: A randomized placebo‐controlled trial , 2011, Hepatology.

[21]  G. Marchesini,et al.  Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. , 2001, Diabetes.

[22]  M. Voiculescu,et al.  Touching some firm ground in the epidemiology of NASH. , 2012, Journal of hepatology.

[23]  H. Makhlouf,et al.  Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver‐related mortality , 2011, Hepatology.

[24]  E. Brunt,et al.  Grading and staging the histopathological lesions of chronic hepatitis: The Knodell histology activity index and beyond , 2000, Hepatology.

[25]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[26]  N. Chalasani,et al.  Endpoints and clinical trial design for nonalcoholic steatohepatitis , 2011, Hepatology.

[27]  K. Clément,et al.  Serum Amyloid A and Obstructive Sleep Apnea Syndrome before and after Surgically-Induced Weight Loss in Morbidly Obese Subjects , 2006, Obesity surgery.

[28]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[29]  G. Pacini,et al.  Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association , 2002, Hepatology.