Mallory-Denk bodies are associated with outcomes and histologic features in patients with chronic hepatitis C

Abstract

Background & aims: Mallory-Denk bodies (MDBs) are inclusions found in hepatocytes of patients with chronic liver diseases. Their clinical significance and prognostic value are not understood.

Methods: We performed cross-sectional and longitudinal analyses of patients with chronic hepatitis C (CHC) enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial to identify clinical features associated with MDBs and changes in MDBs over time. Biopsy specimens were obtained at baseline and 1.5 and 3.5 years after patients were assigned to groups for the HALT-C trial; and patients were followed up to assess clinical and histologic outcomes.

Results: Of biopsy samples collected from 1050 patients, MDBs were present in 15%. They were associated with insulin resistance and laboratory and histologic markers of advanced liver disease (higher levels of periportal fibrosis, pericellular fibrosis, steatosis, and inflammation). After adjusting for disease severity (the ratio of aspartate aminotransferase to alanine aminotransferase, albumin, platelets, fibrosis, steatosis), the presence of MDBs was associated with histologic progression (odds ratio, 1.97; P = .04). Of the 844 patients from whom serial biopsy samples were collected, 61 (7.2%) developed MDBs (MDB gain) and 101 (12.0%) lost MDBs (MDB loss). The presence or absence of diabetes mellitus was associated with MDB gain (P = .006) or loss (P = .024), respectively. Development of MDBs was associated with decompensation (adjusted hazard ratio, 2.81; P < .001) and histologic signs of progression (adjusted odds ratio, 4.02; P = .004).

Conclusions: The presence of MDBs in liver biopsy samples from patients with CHC is associated independently with fibrosis progression. Gain of MDBs over time is associated with decompensation and progression to cirrhosis; and occurs most frequently among diabetic patients. MDBs might be used as prognostic factors for patients with CHC.

Trial registration: ClinicalTrials.gov NCT00006164.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1

Study Design: Cross-sectional analysis (n=1050) and Longitudinal analysis (n=844).

Fig. 2

(A) Representative hematoxylin and eosin staining of a liver biopsy from a patient with CHC (arrow points to a hepatocyte with a ring-like collection of MDBs). (B) Percentage of patients whose baseline biopsies had MDBs present by levels of fibrosis (3–6), zone 3 pericellular fibrosis (0–2), steatosis (0–4), and inflammation (3–12), p

Fig. 3

Kaplan Meier analysis: Time from follow-up biopsy to first clinical event in patients with MDB Gain versus no MDB Gain.