Ubiquitin as a Marker of Cell Injury in Nonalcoholic Steatohepatitis

Abstract

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.

Pathological characterization and morphometric analysis of hepatic lesions in SHRSP5/Dmcr, an experimental non‐alcoholic steatohepatitis model, induced by high‐fat and high‐cholesterol diet

“…Accordingly these bodies may stain immunohistochemically for ubiquitin, M30 or p62 (Banner et al . ; Denk et al . ; Zatloukal et al .…”

Diagnostic Value of Ultrasonographic Examination for Nonalcoholic Steatohepatitis in Morbidly Obese Patients Undergoing Laparoscopic Bariatric Surgery

“…Immunohistochemical staining for unbiquitin was used to help identifying Mallory bodies. 19 The same pathologist (P.L.L.) who was unaware of clinical information and laboratory data examined all the specimens.…”

Metabolic Syndrome Is Related to Nonalcoholic Steatohepatitis in Severely Obese Subjects

“…Liver biopsy with at least 1.0 cm length through left lobe of liver was obtained during surgery, and all the specimens were considered adequate for diagnosis of NASH by the same pathologist. 22 One pathologist unaware of the clinical information and laboratory data examined all specimens (Dr. Phui-Ly Liew). Silver reticulin and Masson trichome stain were used for evaluation of fibrosis and architectural change.…”