Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis

• Published in: Hepatology (Baltimore, Md.) Vol. 10; no. 1; p. 39
• Main Authors: Wang, K K, Czaja, A J, Beaver, S J, Go, V L
• Format: Journal Article
• Language: English
• Published: United States 01-07-1989
• Subjects: Azathioprine - adverse effects; Chronic Disease; Female; Hepatitis - immunology; Hepatitis - therapy; Hepatitis B Surface Antigens - analysis; Humans; Immunosuppressive Agents - adverse effects; Male; Neoplasms - chemically induced; Prednisone - adverse effects; Risk Factors; Time Factors
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840100110

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.