Analysis of keratin genetic variants and Mallory-Denk bodies in patients with chronic hepatitis C:

Investigators:

M. Bishr Omary PhD, MD, Herbert L. Bonkovsky MD

Hypotheses/Aims

Recent literature has begun to uncover the role of keratin proteins in protecting cells from apoptosis and in the formation of Mallory-Denk bodies (MDBs, formerly known as Mallory bodies) that are seen in association with several liver disorders, particularly steatohepatitis but also hepatitis C and hepatocellular carcinoma. In addition, patients with keratin polymorphisms appear to be predisposed to liver disease progression and increased fibrosis.  The first aim of this protocol investigates the association of keratin genetic variants with the severity of chronic hepatitis C and response to therapy. One of our two central hypotheses is that keratin polypeptide 8 and 18 (K8/K18) specific variants predispose to hepatitis C liver disease progression and may modulate response to therapy.

The second aim of this proposal evaluates the association between risk factors such as age (which may related to oxidative stress exposure) and gender and the formation of MDBs in patients with chronic hepatitis C.  Several modifier genes such as K8, p62, TG2 are known to be essential for MDB formation. Our second central hypothesis is that formation of MDBs are related to specific patient characteristics such as gender and age, and may be more prominent in males and patients with older age.