Response to treatment with interferon-alfa in patients with chronic hepatitis C and high titers of -M2, -M4 and -M8 antimitochondrial antibodies.
The prevalence of antimitochondrial antibodies (AMA) in chronic hepatitis C is 2%; titers of AMA are usually low (< 1:40). The prevalence decreases to 0.5% when the results are verified by determination of the M2 subtype (anti-M2, ELISA). In patients in whom both hepatitis C virus (HCV) and AMA are present, the therapeutic decision to give interferon-alfa is complicated, because AMA may be 'real', and if it reflects primary biliary cirrhosis, cholestasis can be triggered or exacerbated. This does not occur when AMA positivity results from induction by hepatotropic C virus; however, this is rarely the case when AMA titers are high (> 1:160).


OBJECTIVE
to undertake a preliminary analysis of the submitochondrial profile of AMA in three patients with chronic hepatitis C and positive AMA titers (> 1:160).


METHODS
we determined antibodies to submitochondrial particles (subtypes) -M2, -M4 and -M8 by ELISA, complement binding (CB) and western immunoblotting with Immunoblot-M2 or WIB-M2 (immunoreactive bands).


RESULTS
two patients were positive for mitochondrial subtypes by ELISA (IgG/IgM subclass) and CB (ELISA M2 470/365 in patient 1 and 600/1370 in patient 2; M4 490/1200 in patient 2. CB M2 1:128, M4 1:64, M8 1:64 in patient 1, M2 1:128 in patient 2). Immunoreactive epitopes (bands) were detected with WIB-M2 for 70, 56, 51, 45 and 36-kDa molecules. Interferon-alfa treatment was unsuccessful, with biochemical exacerbation of cholestasis. In contrast, the patient with no submitochondrial particles according to ELISA, CB and WIB-M2 results responded favorable to this drug.


CONCLUSIONS
these preliminary results suggest that analyses to detect antibodies to submitochondrial particles (-M2, -M4 and -M8 subtypes) and -M2-immunoreactive epitopes in patients with chronic hepatitis C and AMA titers > 1:160 facilitates the diagnosis of primary biliary cirrhosis, and establishes a contraindication for treatment with interferon-alfa despite the presence of HCV infection.
Garrido Palma
G
G
Servicio de Medicina Digestiva, Hospital Universitario La Fe, Valencia, España.
Sánchez Cuenca
J M
JM
Olaso
V
V
Pina
R
R
Urquijo
J J
JJ
López Viedma
B
B
Bustamante
M
M
Berenguer
M
M
Berenguer
J
J
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D001706:Biopsy; D000075202:Contraindications; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood
D000998:Antiviral Agents; D001323:Autoantibodies; D016898:Interferon-alpha; D012367:RNA, Viral