De novo autoimmune hepatitis after interferon treatment in a liver transplant recipient with common variable immunodeficiency

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A 23-year-old female underwent cadaveric liver transplant (LT) for hepatitis C virus (HCV) genotype 1b cirrhosis. The infection was acquired following infusions of contaminated intravenous gammaglobulins that she had been receiving regularly since she was diagnosed of a common variable immunodeficiency (CVID) when she was 15 years of age. The native liver did not show overlapping features of autoimmune hepatitis (AIH). Initial immunosuppression included tacrolimus, azathioprine and prednisone but, due to neurotoxicity, tacrolimus was converted to cyclosporine after the first month. Azathioprine and prednisone were progressively tapered and discontinued 5 and 4 months post-transplant, respectively. At this time the patient presented with increased transaminase levels (Fig. 1) and the viral load was 4.67 × 106 UI/ml. Tests for autoantibodies, including anti-nuclear, anti-mitochondrial, anti-smooth-muscle, anti-liver-kidney microsomal and anti-liver cytosol antibodies were negative. A first biopsy showed signs of chronic active hepatitis C with a Knodell's index of 1-3-4-1:9. When antiviral therapy was commenced with interferon (IFN) α-2b (3 MU 3 times/week) and ribavirin (RBV) (800 mg/day) she was on monotherapy with cyclosporine (50–100 mg/12 h). She had a good response but complete remission of the virus was not achieved (0.6 × 106 UI/ml). Despite of that, the clinicians maintained the treatment but reduced the dose of IFNα-2b to 1.5 MU to avoid rapid progression of HCV which is frequent in patients with CVID. Twenty-two months after LT, another flare in serum aminotransferases developed and the initial dose of 3 MU was restored. Two months later, a new biopsy showed features of chronic active hepatitis with bridging fibrosis, absence of plasma cells in the infiltrates and a Knodell's index of 4-3-4-3:14. A new rise in liver enzymes 34 months after LT, together with the presence of anti-LC1 antibodies, IgG kappa monoclonal gammopathy (3450 mg/dl) and new findings in biopsy, led to the diagnosis of de novo autoimmune hepatitis (AIH). The liver biopsy revealed chronic active hepatitis with bridging fibrosis, important presence of plasma cells in the inflammatory infiltrate (>10%), hepatocyte rosette formation and a Knodell's index of 4-3-4-3:14. Simultaneously, HCV RNA became undetectable. Viral clearance at the time of diagnosis of de novo AIH suggested a temporal relationship between these two events. IFNα-2b +RBV treatment was discontinued and therapy with prednisone (30 mg/day) was started with very good response including progressive normalization of transaminases, reduction of gammaglobulins and complete disappearance of IgG kappa monoclonal gammopathy. This form of de novo AIH, occurring in patients after IFN treatment for HCV recurrence, was described for the first time in 2006 [ 1 Cholongitas E. Samonakis D. Patch D. et al. Induction of autoimmune hepatitis by pegylated interferon in a liver transplant patient with recurrent hepatitis C virus. Transplantation. 2006; 81: 488-490 Crossref PubMed Scopus (45) Google Scholar , 2 Kontorinis N. Agarwal K. Elhajj N. et al. Pegylated interferon-induced immune-mediated hepatitis post-liver transplantation. Liver Transpl. 2006; 12: 827-830 Crossref PubMed Scopus (58) Google Scholar ]. Eleven years after the diagnosis, the patient continues asymptomatic, with normal transaminase levels and IgG values between 600 and 1000 mg/dl. HCV-RNA continues being negative and serum samples are negative for AIH-associated antibodies. Actual treatment consists of cyclosporine (levels around 80 ng/ml) and prednisone (5–7.5 mg/day).