title: Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis.
abstract: To determine the frequency, predisposing factors and consequences of extrahepatic malignancy following long-term immunosuppressive therapy of severe HBsAg-negative chronic active hepatitis, 149 patients who had received prednisone (20 mg daily) or prednisone (10 mg daily) in combination with azathioprine (50 mg daily) for at least 6 months were evaluated systematically for 109 +/- 5 months (range: 7 to 223 months). Seven neoplasms involving cervix (2), lymphatic tissue (1), breast (1), bladder (1), soft tissue (1) and unknown site (1) developed in seven patients after 116 +/- 23 months (range: 18 to 164 months). The incidence of extrahepatic neoplasm was 1 per 194 patient-years of surveillance, and the probability of tumor occurrence was 3% after 10 years. Tumor frequency was similar in men and women and the risk was 1.4-fold greater than that in an age- and sex-matched normal population (95% confidence interval, 0.6- to 2.9-fold normal). Patients with extrahepatic malignancy were not distinguished by age, sex, treatment regimen, cumulative duration of treatment (42 +/- 9 vs. 60 +/- 4 months, p = 0.7) or individual features of the liver disease. Five of the seven patients survived during 48 +/- 25 months of follow-up, including two patients who have lived for at least 5 years after the diagnosis of malignancy. We conclude that extrahepatic malignancy develops infrequently during long-term immunosuppressive therapy. Its occurrence is not related to the type or duration of treatment, and long-term survival after tumor detection is possible. The low but probably increased risk of extrahepatic neoplasm does not militate against the use of immunosuppressive therapy in these patients.
authors.affiliation: Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: K K
authors.initials: KK
authors.lastname: Wang
authors.forename: A J
authors.initials: AJ
authors.lastname: Czaja
authors.forename: S J
authors.initials: SJ
authors.lastname: Beaver
authors.forename: V L
authors.initials: VL
authors.lastname: Go
mesh_terms: D001379:Azathioprine / Q000009:adverse effects; D002908:Chronic Disease; D005260:Female; D006505:Hepatitis / Q000276:immunology / Q000628:therapy*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D009369:Neoplasms / Q000139:chemically induced*; D011241:Prednisone / Q000009:adverse effects; D012307:Risk Factors; D013997:Time Factors
chemical_list: D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone