Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection.
It has been reported that patients with chronic hepatitis C show significantly reduced CPY3A4 and CYP2D6 activity in comparison with healthy volunteers (Becquemont et al., 2002).
This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients.
However, LKM autoantibodies are also detected in a small percentage of patients with chronic hepatitis C. The autoantigen to anti-LKM-1 has been identified to be CYP2D6.
Eukaryotically expressed CYP2D6 is the universal target of liver kidney microsomal Ab type 1 (LKM1) in both type 2 autoimmune hepatitis (AIH) and chronic hepatitis C virus (HCV) infection.
These findings suggest that a genetic predisposition to produce the enzyme CYP2D6 of extensive metabolizer-type is associated with the induction of anti-LKM-1 in chronic hepatitis C patients.
Thus, the sera of patients with autoimmune hepatitis type II and patients with chronic hepatitis C recognize different antigenic epitopes of the CYP2D6 molecule.