Liver toxicity is a common side effect of antituberculosis (anti-TB) drugs. We studied the differences in liver dysfunction observed during anti-TB treatment between hepatitis B virus carriers (HBV) and noncarriers. Three hundred twentyfour patients on anti-TB drugs were recruited and followed up for 1 year. Forty-three patients with HBV and 276 non-HBV patients were included for analysis. Liver function tests and viral markers were monitored monthly. Liver biopsy was requested whenever the alanine transaminase (ALT) was persistently abnormal. Eighty-six HBV carriers who were not given anti-TB drugs were chosen as a second control and evaluated prospectively. The incidence of liver dysfunction was significantly higher in HBV carriers given anti-TB drugs (34.9%) when compared to noncarriers (9.4%, P Ͻ .001) and with HBV carriers not given anti-TB drugs (8.1%, P Ͻ .001). For patients given anti-TB drugs, HBV carriers who developed liver dysfunction were younger (P ϭ .011) and had more severe liver injury compared with noncarriers (P ϭ .008). By multiple logistic regression analysis, age (P ϭ .002) and hepatitis B infection (P Ͻ .001) were the only 2 significant risk factors for hepatotoxicity related to anti-TB therapy. (HEPATOLOGY 2000;31:201-206.)Recently, there has been a resurgence of tuberculosis (TB) in a number of countries. 1,2 It has been estimated that approximately one third of the world' s population is infected with Mycobacterium tuberculosis. This reservoir of infected person results in 8 million new cases of TB and 2.9 million deaths annually. 1 TB and hepatitis B virus (HBV) infection are both endemic in South East Asia. In Hong Kong, the notification rate for TB was 103 persons per 100,000 population in 1996. 3 Approximately 10% of Hong Kong' s population are chronic HBV carriers. 4 Currently, the short-course program for the treatment of TB in Hong Kong begins with a 2-month course of 4 drugs, namely isoniazid, rifampicin, pyrazinamide, and ethambutol. This is followed by a continuation phase of 4 months with the 2 drugs, isoniazid and rifampicin. 3,5,6 Hepatotoxicity is the major adverse effect of isoniazid, rifampicin, and pyrazinamide. 7-10 Chronic hepatitis B 6,11,12 infection has been suggested as a possible risk factor for the development of liver dysfunction caused by anti-TB drugs. 13 However, studies of the effect of chronic hepatitis B carriage on the hepatotoxicity of anti-TB drugs have been unable to show any definite deleterious consequences. 11,14 McGlynn et al. 11 performed a retrospective analysis of isoniazid prophylaxis in 1,833 Asian patients in 1986; Hwang et al. 14 performed a prospective study in 240 Taiwanese patients in 1997. Both studies failed to identify hepatitis B infection as a risk factor for the development of liver dysfunction. None of the studies published to date have assessed the degree of liver damage by histology. There was no attempt made to differentiate between drug-induced damage and damage caused by hepatitis B viral activity. We report a prospective stu...

It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in treatment of 162 (84%) patients, macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10% to 124%) and 55% (10% to 121%), respectively. Defining significant associations by risk ratios > 1.2 or < 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other group 5 drugs with respect to outcome for patients treated with linezolid, although selection bias might have led to underestimation of their effects. Our findings substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.

The rate of active TB and TB infection in old age homes in Hong Kong is still high. Because treatment for latent TB carries a high risk for liver dysfunction in this population, clinicians and other healthcare workers need a high index of suspicion and to diagnose and treat this disease as early as possible to prevent transmission.