Hepatotoxicity from antituberculous therapy in the elderly: A systematic review

Abstract

Summary Background Elderly persons have the highest rates of tuberculosis (TB) in the United States compared to all other age groups. A systematic literature review was conducted to determine if older age was a risk factor for hepatotoxicity resulting from treatment with first-line drugs used to treat active (TB) and latent tuberculosis (LTBI). Methods A systematic review of MEDLINE, Cochrane Controlled Trial Registry, CINAHL®, and Science Citation Index Expanded (from 1970 to 2011) was performed to determine the risk of hepatotoxicity, comparing those over 60 with those under 60. A meta-analysis was performed using a random effects model along with log odds ratios and the chi-square test. Findings Thirty-eight studies (40,034 participants; 1208 cases of hepatotoxicity) met the selection criteria. For active TB, an overall mean effect of 0.277 (p = 0.024, 95% CI: 0.037–0.517) was observed, which is equivalent to an odds ratio of 1.32 (95% CI: 1.04–1.68). For LTBI, an overall mean effect of 1.42 (p < 0.001, 95% CI: 0.794–2.05) was observed, which translates to an odds ratio of 4.14 (95% CI: 2.21 –7.74). Interpretation Our analysis revealed that patients older than 60 had significantly more risk of hepatotoxicity. These studies suggest that a gentler regimen of treatment for older individuals could benefit health outcomes in this population of TB patients and minimize risks to the public's health.

Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB centre in the UK

“…Most notably, increasing age was not found to be a risk factor which is consistent with other studies [5, 8]. This may be because only 16.2% of cases were over 65 years of age and because older patients are considered at high risk for DILI, we often omitted pyrazinamide in these patients and monitored them more carefully for side effects [14].…”

Does tuberculosis threaten our ageing populations?

“…Elderly people are more likely to develop adverse drug reactions from polypharmacy, existing co-morbidities and age-related physiological changes. Hepatotoxicity is a common adverse effect as a result of treatment with isoniazid, rifampicin and pyrazinamide, ranging from mild reversible abnormalities of transaminases to fulminant liver failure, and hepatotoxicity from anti-tuberculous drugs rises significantly with increasing age [ 38 , 55 , 56 ]. TB drug related hepatotoxicity in those older than 65 years incurs an odds ratio of 1.71 (CI 95 % 1.24–2.35) [ 56 ], although cessation of isoniazid therapy due to suspected hepatotoxicity is not associated with increasing age [ 57 ].…”

Plasmapheresis in Tuberculosis Treatment

“…xic hepatitis risk is the highest in elderly patients [23]. At the same time, the total bilirubin increased level above 5 mg/dl is a poor forecast [24].…”