A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases.

BACKGROUND AND OBJECTIVES

Viral hepatitis due to hepatitis C virus results in chronic liver disease in more than 70% of individuals infected with the virus. Hepatitis C virus is also thought to be the cause of autoimmune chronic hepatitis, type II. The only treatment for chronic hepatitis C is interferon (IFN). IFN is both an antiviral agent and an up regulator of the cellular immune system. The latter effect is non-specific. Thus, IFN diffusely activates the cellular immune system and can initiate new autoimmune diseases in patients treated with it. To determine the prevalence of autoantibodies in patients with chronic hepatitis C and in patients with autoimmune hepatitis and to determine the incidence of new onset autoimmune disease in IFN-treated subjects with chronic hepatitis C, the records of 323 unselected patients with chronic hepatitis were reviewed.

MATERIAL AND METHODS

A total of 203 patients with a mean age of 45.7 +/- 0.8, ranging 18-81 with either HCV disease or autoimmune hepatitis, were identified and studied. One hundred sixty-two patients with chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT) for at least 6 months, the presence of detectable anti-HCV (HCV; second generation enzyme immunoassay [EIA2], a positive recombinant immunoblot assay [RIBA], the presence of HCV-RNA by PCR in serum and an abnormal biopsy consistent with chronic hepatitis C) were identified. Each was also negative for HbsAg, HbeAg and anti-Delta. Forty-one patients with a putative autoimmune chronic hepatitis (AIH) diagnosed on the basis of serologic positivity for classical autoantibodies (ANA and anti-smooth muscle antibodies), tissue typing (B8, Dr3 positive), characteristic liver biopsy findings and the absence of anti-HCV and HCV-RNA in serum were identified. The records of both of these groups of patients were reviewed for the following antibodies: anti-nuclear antibodies (ANA), antimitochondrial antibodies (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibodies (SMA), anti-microsomal antibodies (MSA).

RESULTS

The rate of ANA positivity was 63% in both groups; the rate of SMA positivity was 65% in patients with HCV infection (group I) and 63% in patients with AIH (group II). AMA was positive in 4% of the subjects in group I and 50% of the subjects in group II; anti-LKM antibodies were absent in all 91 HCV cases and were present in 4% of the cases in group II; MSA positivity was present in 17% of group I and 10% of group II. Eighty-one of the one hundred sixty-two patients (50%) with chronic hepatitis C received IFN treatment at a dose of 5 MU SQ daily for 6 months. Thirty-two of these eighty-one patients (42 females and 39 males with a mean age of 45.0 +/- 1.3, ranging from 18 to 81 yr.) had at least two autoantibodies detectable prior to the IFN therapy (subgroup 1) and 49 had one or no identifiable autoantibodies (subgroup 2) present prior to IFN therapy. No significant differences in the interferon response rate defined by HCV-RNA negativity and normalization of serum ALT levels at the end of therapy was noted between those with autoantibodies and those without autoantibodies. Fifteen of the interferon-treated patients developed a clinical manifestation of a new onset autoimmune disease during the course of their interferon treatment. Six of the fifteen patients belonged to subgroup 1 (n = 32) and the remaining 9 patients to subgroup 2 (n = 49) (p > 0.05). None were managed by discontinuing the interferon. Most required some form of specific treatment.(ABSTRACT TRUNCATED)