The prevalence, clinical features and response to antiviral therapy of patients with chronic hepatitis C who are seropositive for liver-kidney microsome type 1 antibodies.
BACKGROUND
Antibodies to liver-kidney microsome type 1 (anti-LKM-1), which are a marker of autoimmune hepatitis, are found in a minority of patients with chronic hepatitis C virus (HCV) infection. Whether interferon/ribavirin therapy is safe and effective in these patients is unclear.


OBJECTIVE
To describe the prevalence, clinical features and response to interferon/ribavirin therapy of anti-LKM-1 seropositive patients with chronic hepatitis C.


METHODS
All anti-LKM-1 seropositive patients with chronic hepatitis C who between 1997 and 2002 underwent a diagnostic liver biopsy at the Liver Center Maggiore Hospital, Milan, were studied. Serum HCV RNA was tested by in-house PCR with a limit sensitivity of 50 IU/ml. Tissue antibodies were assessed by indirect immunofluorescence on cryostat sections from rat liver, kidney and stomach. Liver biopsies were graded and staged by the Ishak score. Autoimmune hepatitis was defined according to the International Autoimmune Hepatitis Grading (IAHG) score.


RESULTS
Forty-eight (1.8%) of 2675 HCV patients circulated anti-LKM-1 (30 females, 55 years of age). Twenty-eight had genotype 2, 18 genotype 1, and two genotype 3. Aminotransferase levels had been high for 23 + 12 years, on average. Using IAHG, autoimmune hepatitis was excluded in 44 patients (92%) and found to be probable in 4 patients (8%). Chronic hepatitis was histologically mild in 34 patients (70%), moderate to severe in 7 patients (15%) and with cirrhosis in 7 patients (15%). A sustained virological response (SVR) was achieved in 20 of the 27 patients who received interferon/ribavirin (13 genotype 2c with 87% SVR, and 7 genotype 1b with 58% SVR). None of the patients had serum aminotransferases, immunoglobulins or anti-LKM-1 levels flaring following therapy.


CONCLUSIONS
LKM-1 antibodies rarely occur in patients with chronic hepatitis C and do not predict autoimmune hepatitis, interferon/ribavirin hyporesponsiveness or immune-related reactions to therapy.
Monti
Valentina
V
A.M. Et A. Migliavacca Center for Liver Disease, Department of Gastroenterology and Endocrinology, IRCCS Maggiore Hospital Fondazione Policlinico, Mangiagalli, Regina Elena and University of Milan, Milan, Italy.
Aghemo
Alessio
A
Rumi
Maria Grazia
MG
Donato
Maria Francesca
MF
Del Ninno
Ersilio
E
Colombo
Massimo
M
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D015995:Prevalence; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C060729:anti-liver kidney microsome antibody; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons; C417083:peginterferon alfa-2b