Research Article: Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase

Date Published: May 7, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Etienne Mokondjimobe, Benjamin Longo-Mbenza, Jean Akiana, Ulrich Oswald Ndalla, Regis Dossou-Yovo, Joseph Mboussa, Henri-Joseph Parra.


Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7 ± 5.8 years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.

Partial Text

The concept of biomarkers is very important in this paper. The role of biomarkers is now exponentially increasing in guiding decisions in drug development and personalized medicine. A biomarker is not predictive or casual to a disease, but it can predict patients’ response to compound by identifying certain patient groups that are more likely to response to the drug therapy or to avoid specific adverse events [1].

In this study, the incidence of ADR was only 3%, accidental, transient, benign and due to self-administration of cotrimoxazole. This rate of elevation of hepatic transaminases was within the traditional interval [7], but lower than the levels of 50–75% ADR reported in Eastern European and Asian countries [17]. ADR occurred within the first 30 days of the initiation of anti-TB treatment as usually reported by different studies [17, 18]. Concomitant use of cotrimoxazole or other hepatotoxic drugs is well established as a risk factor for anti-TB-induced liver injury [7, 9, 11, 12].

The present study will have significant implications in understanding the role of oxidative stress biomarkers and that of liver enzymes in personalizing the DOTS. Systematic steps for prevention of hepatotoxicity are recommended in anti-TB therapy. These recommendations include patient and regimen selection to optimise benefits over risks. Education of patients to avoid self-administration of medications interfering with anti-TB drugs is mandatory.

This study concludes that oxidative stress markers within normal range before starting anti-TB treatment and considering conditions related to hepatotoxicity in patients admitted for active PTB might predict excellent tolerability of anti-TB drugs and very low rate of ADR.