title: Anti-tuberculosis treatments and risk of hepatocellular carcinoma in tuberculosis patients with liver cirrhosis: a population-based case-control study.
abstract: The objective of this study was to evaluate the association between the use of anti-tuberculosis (anti-TB) agents, isoniazid (INH), rifampicin (RIF), and their combination (INH + RIF), and the risk of hepatocellular carcinoma (HCC) in cirrhotic patients. This population-based case-control study was conducted using a research database of Taiwan's National Health Insurance program. Cirrhotic patients first diagnosed with HCC between 1996 and 2011 (n = 50,351), among whom 4,738 were anti-TB medication users, were evaluated. Cirrhotic patients who did not develop HCC within the same period, frequency-matched according to age, sex, and index year, were evaluated as the control group (n = 47,488). The adjusted odds ratio (OR) of HCC was 1.34 [95 % confidence interval (CI), 1.20-1.50] in INH + RIF users compared with non-INH + RIF users. Long-term (>12 months) use of INH, RIF, and INH + RIF was significantly associated with increased risk of HCC, with an adjusted OR of 3.51 (95 % CI, 2.11-5.84), 4.17 (95 % CI, 2.76-4.31), and 7.17 (95 % CI, 4.08-12.6), respectively, after adjusting for age, sex, and comorbidities. An average dose of INH + RIF >16,050 mg/year was associated with increased risk of HCC in cirrhotic patients, with an adjusted OR of 1.48 (95 % CI, 1.27-1.73). Our results indicate that cirrhotic patients with long-term or high-dose INH and RIF treatment, particularly their combination, are associated with increased risk of HCC development.
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Lim
authors.forename: C-L
authors.initials: CL
authors.lastname: Lin
authors.forename: D-Z
authors.initials: DZ
authors.lastname: Hung
authors.forename: Y-N
authors.initials: YN
authors.lastname: Lin
authors.forename: C-H
authors.initials: CH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D018570:Risk Assessment; D013624:Taiwan; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin