Risk Factors for Liver Injury with an Elevated Serum Bilirubin Concentration Caused by Antituberculous Drugs

Abstract

Objective No studies have so far sufficiently investigated the risk factors for drug-induced liver injury (DILI) with an elevated serum bilirubin concentration. Methods We conducted a historical cohort study observing inpatients admitted to two hospitals in Japan. A decreased level of activities of daily living (ADL) was defined as a Barthel Index score of <80. The patients were treated with standard regimens under a directly observed treatment short-course strategy. Results The cohort of 356 patients comprised 244 men (68.5%) and 112 women (31.5%), with a mean age of 63.8±20.2 years. Compared with the patients who did not experience DILI with a bilirubin level of ! 2.0 mg/dL, the patients who experienced DILI with a bilirubin level of ! 2.0 mg/dL more often had a decreased level of ADLs, were more likely to suffer from chronic cardiac disease, had lower serum albumin levels and were less often treated with four-drug regimens involving pyrazinamide (PZA). In a logistic regression analysis in which these five factors acted as independent variables, a decreased level of ADLs was the strongest predictor for DILI with a bilirubin level of ! 2.0 mg/dL, with an odds ratio of 16.5 (95%CI: 1.7-159; p= 0.015), followed by chronic cardiac disease, with an odds ratio of 4.0 (95%CI: 1.2-12.6; p=0.020). Conclusion A decreased level of ADLs and chronic cardiac disease are strong risk factors for DILI with a bilirubin level of ! 2.0 mg/dL resulting from the use of antituberculous drugs. Physicians should pay close attention to the possibility of DILI with a bilirubin level of ! 2.0 mg/dL when treating tuberculosis patients with a decreased level of ADLs and/or chronic heart disease.

Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients

“…[ 12 ] The PZA has also been demonstrated to contribute to increased incidence or severity of hepatotoxicity. [ 13 ] Kato et al .,[ 14 ] have observed decreased activities of daily living and chronic cardiac disease to be associated with higher prevalence of DILI with bilirubin >2 mg/dl in patients with anti-tubercular therapy. Elderly patients are at a higher risk of development of DILI than younger generation.…”

Prevalence of Hepatotoxicity From Antituberculosis Therapy

“…8,9 Decreased activities of daily living and chronic heart disease have been associated with a higher prevalence of DILI with bilirubin >34 µmol/L in patients receiving ATT. 10 The reported prevalence of DILI in different anti-TB chemotherapy that included INH, RMP, and PZA ranged from 0.6% to 3% 4,11,12 and among all the first-line ATT agents, PZA is the most common cause of DILI. 13 From an analysis of pooled data from 4 prospective Indian studies with DOTS, 14,15 the risk of DILI was found to be 11.5%, whereas meta-analysis of 14 studies from the west found the same risk to be 4.28%.…”