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 re sults in chronic liver disease in more than 70% of individuals infecte d 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 a n up regulator of the cellular immune system. The latter effect is non -specific. Thus, IFN diffusely activates the cellular immune system an d can initiate new autoimmune diseases in patients treated with it. To determine the prevalence of autoantibodies in patients with chronic h epatitis 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. Materials 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 hun dred sixty-two patients with chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT) for at least 6 months, the pr esence of detectable anti-HCV (HCV; second generation enzyme immunoass ay [EIA2], a positive recombinant immunoblot assay [RIBA], the presenc e of HCV-RNA by PCR in serum and an abnormal biopsy consistent with ch ronic hepatitis C) were identified. Each was also negative for HbsAg, HbeAg and anti-Delta. Forty-one patients with a putative autoimmune ch ronic hepatitis (AIH) diagnosed on the basis of serologic positivity f or classical autoantibodies (ANA and anti-smooth muscle antibodies), t issue 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 foll owing antibodies: anti-nuclear antibodies (ANA), anti-mitochondrial an tibodies (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smoo th muscle antibodies (SMA), anti-microsomal antibodies (MSA). Results: The rate of ANA positivity was 63% in both groups; the rate of SMA po sitivity was 65% in patients with HCV infection (group I) and 63% in p atients 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 gro up II; MSA positivity ws 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 mo nths. 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 leas t 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 res ponse rate defined by HCV-RNA negativity and normalization of serum AL T levels at the end of therapy was noted between those with autoantibo dies and those without autoantibodies. Fifteen of the interferon-treat ed patients developed a clinical manifestation of a new onset autoimmu ne disease during the course of their interferon treatment. Six of the fifteen patients belonged to subgroup 1 (n=32) and the remaining 9 pa tients to subgroup 2 (n=49) (p>0.05). None were managed by discontinui ng the interferon. Most required some form of specific treatment. Conc lusion: It can be concluded that: 1) ANA and SMA are positive at simil ar frequencies in patients with chronic hepatitis C and autoimmune hep atitis; 2) anti-LKM antibodies are absent or rarely detected in patien ts with HCV infection seen in Oklahoma City; 3) anti-HCV testing and H CV-RNA testing were the only tests that distinguished AIH from chronic HCV infection; 4) new onset autoimmune conditions can develop during the course of interferon treatment and occur at similar rates in those with and without pre-existing autoantibodies; 5) when a new onset aut oimmune disease occurs during IFN treatment, it does not necessarily r equire discontinuation of the IFN therapy; 6) however, it often requir es specific therapy; 7) the overall incidence of new onset autoimmune disease was 18.5% in 81 patients with chronic HCV treated by IFN.