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The Use of Protein Tyrosine Phosphatase 1B and Insulin Receptor Immunostains to Differentiate Nonalcoholic From Alcoholic Steatohepatitis in Liver Biopsy Specimens

Schuyler O. Sanderson MD, Thomas C. Smyrk MD
DOI: http://dx.doi.org/10.1309/1PX2LMPQUH1EE12U 503-509 First published online: 1 April 2005


Nonalcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) typically are indistinguishable histologically. The diagnosis relies on reporting of alcohol consumption. The metabolic syndrome involving insulin resistance is associated with nonalcoholic fatty liver disease (NAFLD). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates the insulin receptor (IR). Increased PTP1B expression is seen in obesity and possibly is responsible for the insulin resistance seen in the metabolic syndrome. The study objective was to determine whether biopsy specimens with steatohepatitis could be classified accurately as alcoholic or nonalcoholic by immunohistochemical stains. We selected 241 cases of steatohepatitis, comprising 53 and 188 cases of alcoholic and NAFLD, respectively. Specimens were stained with PTP1B and IR (β subunit) and classified as NASH or ASH. The staining pattern predicted 60 cases of ASH and 181 cases of NASH. Results correlated with clinical diagnoses in 70% and 88% of ASH and NASH cases, respectively (odds ratio, 16.6; 95% confidence interval, 8.2–35.4).

Key Words:
  • Nonalcoholic steatohepatitis
  • NASH
  • Obesity
  • Insulin resistance
  • Immunohistochemistry
  • Cirrhosis