Interferon therapy in LKM-1 positive patients with chronic hepatitis C: follow-up by a quantitative radioligand assay for CYP2D6 antibody detection.
OBJECTIVE
Liver/kidney microsomal type 1 (LKM-1) antibodies described by indirect immunofluorescence using frozen sections of kidney, stomach and rat liver define a group of patients with type 2 autoimmune hepatitis. Sera react with a non-glycosylated 50-kD protein of the endoplasmic reticulum, which was recently identified as cytochrome P4502D6 (CYP2D6). LKM-1 antibodies may also be associated with hepatitis C virus infection (HCV+/LKM-1+). For this subset of patients, the choice of steroids or interferon alpha therapy may be difficult because of the association of hepatitis C virus infection and autoimmune manifestations. Recently we developed a quantitative immunoprecipitation radioligand assay using 35S-methionine-labeled CYP2D6 protein produced by in vitro transcription and translation reaction. This method detects antibodies against linear and conformational epitopes in both AIH-2 and HCV+/LKM-1+ patients. The aim of this study was to analyze the time-course of HCV+/LKM-1+ patients, applying our radioligand assay over a long follow-up.


METHODS
We studied five patients who were positive for CYP2D6 antibodies from among 235 chronic hepatitis C virus hepatitis patients (2.1%) treated with interferon alpha for a minimal follow-up of 2 years. We analyzed LKM-1 antibody titer sequentially by radioligand assay, HCV RNA titer and alanine aminotransferase activity in these patients.


RESULTS
We found no aggravation of liver disease in this group of patients. Three of these patients showed a sustained biochemical and virological response after interferon. Two others responded partially to interferon therapy. Alanine aminotransferase levels and HCV-RNA decreased during interferon therapy in responder patients. CYP2D6 antibodies did not change in three responder patients during follow-up. One responder patient decreased CYP2D6 antibody level by radioligand assay, but indirect immunofluorescence titers showed a similar pattern. One partial responder patient decreased CYP2D6 antibody level but was negative by indirect immunofluorescence.


CONCLUSIONS
Our results show that patients with hepatitis C virus who are positive for CYP2D6 antibodies may be treated with interferon, and respond in the same way as CYP2D6 antibody negative patients. Radioligand assay could be helpful for monitoring HCV+/LKM-1+ patients receiving interferon therapy.
Duclos-Vallée
J C
JC
Service d'Immunologie, Hôpital Necker, Paris, France.
Nishioka
M
M
Hosomi
N
N
Arima
K
K
Leclercq
A
A
Bach
J F
JF
Yamamoto
A M
AM
D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D005838:Genotype; D006684:HLA-DR Antigens / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D051381:Rats; D013997:Time Factors
D000998:Antiviral Agents; D001323:Autoantibodies; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; C060729:anti-liver kidney microsome antibody; D007372:Interferons; D019389:Cytochrome P-450 CYP2D6; D000410:Alanine Transaminase