GASTROENTEROLOGY 1990;99:502-504 BRIEF REPORTS Isoniazid-R .ifampin-Induced Hepatitis in Hepatitis B Carriers JAW-CHING WU, SHOU-DONG LEE, PEN-FENG YEH, CHO-YU CHAN, YAN-JENN WANG, YI-SHIN HUANG, YANG-TE TSAI, PUI-YUEN LEE, LING-PA1 TING, and KWANG-JUEI LO Division of Gastroenterology. Departments of Medicine and Chest Medicine, Veterans General Hospital; Graduate Institutes of Clinical Medicine, Microbiology, and Immunology, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China From January 1984-December 1987, 1783 patients received combination therapy of isoniazid, rifampin, and ethambutol for the control of tuberculosis. Forty- two developed symptomatic hepatitis during the period of treatment. Fifteen were hepatitis B virus carriers, and the remaining 27 were noncarriers. The peak serum transaminase and bilirubin levels were higher in carriers. Seven carriers died of fulminant or subacute hepatic failure, and only 1 noncarrier died. Eleven carriers had detectable serum hepatitis B virus deoxyribonucleic acid during the acute stage of hepatitis. The roles of isoniazid-rifampin combina- tion therapy and hepatitis B virus in the adverse outcomes of carriers were discussed. H epatitis B virus (HBV) infection is highly preva- lent in Taiwan; 15% of the adult population are HBV carriers (1). Also, tuberculosis (TBc) is still com- mon in this area (2). Acute hepatitis episodes occurring in HBV carriers and noncarriers while they are receiv- ing anti-TBc drugs are not rare in our daily practice. The problem of carriers having more severe hepatitis and unfavorable outcomes is of great concern. Re- cently, McGlynn et al. (3) report that there is no evidence of more hepatotoxicity of the prophylactic use of isoniazid (INH) in carriers than in noncarriers. However, their study focuses on the prophylactic use of INH alone in patients with positive tuberculin tests (not clinical tuberculosis) under the age of 35. Previous reports (4-6) indicate that aged patients are more prone to develop isoniazid-induced hepatitis. Also, combination treatment of INH and rifampin (RIF] and underlying liver disease are reported to be risk factors for the development of severe hepatitis (6-8). We herein report adverse outcomes in a group of aged HBV carriers who developed hepatitis while receiv- ing INH-RIF therapy for active TBc. We analyzed the characteristics, patterns of clinical course, and status of HBV replication in these carriers and compared them with those of other patients who had more favorable outcomes. Materials and Methods Patients From January 1984-December 1987, a total of 1,783 patients received a combination therapy (300 mg of INH, 450-600 mg of RIF, and 1,200 mg of ethambutol) for the control of active TBc. Forty-two patients developed symptom- atic hepatitis during the period of treatment. They were then admitted, and thus included into this study. Classification of Clinical Manifestations The clinical manifestations were classified accord- ing to history of liver disease, the course of disease progres- sion, and outcomes. Four patterns of clinical manifestations were observed: 1. Pattern 1: patients who had a history of liver disease and elevated serum ALT levels before the start of anti-TBc treatment. Their serum ALT levels fluctuated through the period of treatment and remained so after the discontinu- ation of drugs. 2. Pattern 2: patients who had no history of liver disease or who had a long remission period before the start of Abbreviations used in this paper: Anti-HD, antibody against hepatitis D antigen; IgM anti-HBc, immunoglobulin M antibody against hepatitis B core antigen; INH, isoniazid; RIF, rifampin; TBc, tuberculosis. 0 1990 by the American Gastroenterological Association 0016-5065/90/$3.00