Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis

UMMS Affiliation

Dept of Pathology; Department of Medicine and the Liver-Biliary-Pancreatic Center

Publication Date


Document Type



Adult; Aged; Biopsy, Needle; Fatty Liver; Female; HLA Antigens; Histocompatibility Antigens Class I; Humans; Immunohistochemistry; Male; *Membrane Proteins; Middle Aged; Mutation; Proteins; Ubiquitins


Cancer Biology | Immunopathology


Ubiquitin (UB), an intracellular protein that binds to other proteins to target them for proteolysis, is associated with Mallory hyalin (MH), which supports a biopsy diagnosis of nonalcoholic steatohepatitis (NASH). We analyzed 54 liver biopsy specimens from 49 patients with a clinical diagnosis of NASH for immunoreactive UB and multiple features of necroinflammation, fibrosis, and Prussian blue-positive iron to determine whether the presence of immunoreactive UB increases detection of MH or correlates with other features of cell injury or mutations of the HFE gene. MH and UB were graded. Analysis for HFE gene mutations was performed in 48 patients. Biopsy diagnoses were distributed as follows: NASH, 42; steatosis, 10; and nonspecific changes, 2. UB was present in 20 specimens and MH in 23. Of 31 specimens with 0 MH, 6 had UB; of 14 with 1 + (questionable) MH, 7 had 1+ or 2+ UB. UB correlated positively and significantly with the diagnosis and grade of NASH, presence of MH, cell swelling, lobular inflammation, and fibrosis. Immunostaining for UB may enhance detection of MH in questionable cases, support the diagnosis of NASH, and indicate which patients may be at risk for progression of disease.

DOI of Published Version



Am J Clin Pathol. 2000 Dec;114(6):860-6. Link to article on publisher’s site

Journal/Book/Conference Title

American journal of clinical pathology

Related Resources

Link to article in PubMed

PubMed ID