Ubiquitin as a marker of cell Injury in nonalcoholic steatohepatitis

Ubiquitin (UB) an intracellular protein that binds to other proteins to tar get them for proteolysis, is associated with Mallory hyalin (MH), which sup ports a biopsy diagnosis of nonalcoholic steatohepatitis (NASH). We analyze d 54 liver biopsy specimens from 49 patients with a clinical diagnosis of N ASH for immunoreactive UB and multiple features of necroinflammation, fibro sis, and Prussian blue-positive iron to determine whether the presence of i mmunoreactive UB increases detection of MH or correlates with other feature s of cell injury or mutations of the HFE gene. MH and UB were graded Analys is for HFE gene mutations was performed in 48 patients. Biopsy diagnoses we re 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 correlat ed positively and significantly with the diagnosis and grade of NASH, prese nce of MH, cell swelling, lobular inflammation, and fibrosis. Immunostainin g for UB may enhance detection of MH in questionable cases, support the dia gnosis of NASH, and indicate which patients may be at risk for progression of disease.