Anti-tuberculosis treatments and risk of hepatocellular carcinoma in tuberculosis patients with liver cirrhosis: a population-based case–control study

• Published in: European journal of clinical microbiology & infectious diseases Vol. 34; no. 3; pp. 479 - 485
• Main Authors: Lim, Y.-P., Lin, C.-L., Hung, D.-Z., Lin, Y.-N., Kao, C.-H.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2015; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antitubercular Agents - adverse effects; Antitubercular Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Carcinoma, Hepatocellular - epidemiology; Case studies; Case-Control Studies; Drug dosages; Drug Therapy, Combination - adverse effects; Drug Therapy, Combination - methods; Female; Hospitals; Humans; Illnesses; Infectious diseases; Internal Medicine; Isoniazid - adverse effects; Isoniazid - therapeutic use; Liver cancer; Liver cirrhosis; Liver Cirrhosis - complications; Liver diseases; Male; Medical Microbiology; Medicine; Middle Aged; Mortality; Mycobacterium; National health insurance; Pharmacy; Population; Public health; Rifampin - adverse effects; Rifampin - therapeutic use; Risk; Risk Assessment; Taiwan; Toxicity; Tuberculosis; Tuberculosis - complications; Tuberculosis - drug therapy; Young Adult; Taiwan; China; National Health Insurance Program; National Health Research Institute; National Health Insurance Research Database; Cirrhotic Patient; National Health Insurance Database
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-014-2251-3

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.