Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children.
OBJECTIVE
To evaluate the clinical pattern and evolution of chronic hepatitis C in children with liver/kidney microsomal antibody type 1 autoantibodies (LKM1).


METHODS
A multicenter, retrospective study, including the following groups of children with hepatitis C virus infection: (1). 21 consecutive LKM1-positive patients, (2). 42 age- and sex- matched LKM1-negative patients, and (3). 4 interferon-induced LKM1-positive cases. LKM1 reactivity to human microsomes and recombinant cytochrome P450IID6 (CYP2D6) was assayed by immunoblotting.


RESULTS
Clinical and biochemical features overlapped in LKM1-positive and LKM1-negative children, but a fibrosis score >3 (range 0-6) was significantly more frequent (P =.04) in the former. Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Five of 7 LKM1-positive children treated with interferon had an ALT exacerbation.


CONCLUSIONS
LKM1-positive hepatitis C in children is characterized by a wide spectrum of biochemical, serologic, and histologic features. Whether autoimmunity may contribute to liver damage in a subgroup of patients with more severe liver disease, high LKM1 titers, and reactivity to CYP2D6 is a question deserving further investigation.
Bortolotti
Flavia
F
Department of Pediatrics, University of Padua, Padua, Italy.
Muratori
Luigi
L
Jara
Paloma
P
Hierro
Loreto
L
Verucchi
Gabriella
G
Giacchino
Raffaella
R
Barbera
Cristiana
C
Zancan
Lucia
L
Guido
Maria
M
Resti
Massimo
M
Pedditzi
Sabrina
S
Bianchi
Francesco
F
Gatta
Angelo
A
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D001706:Biopsy; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism*; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007370:Interferon Type I / Q000627:therapeutic use; D007558:Italy / Q000453:epidemiology; D008297:Male; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013030:Spain / Q000453:epidemiology; D013256:Steroids; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D001323:Autoantibodies; D007370:Interferon Type I; D011994:Recombinant Proteins; D013256:Steroids; C060729:anti-liver kidney microsome antibody; D019389:Cytochrome P-450 CYP2D6; D000410:Alanine Transaminase