Effect Of Anti-tuberculosis Treatment Research Articles

Fulminant Hepatitis Secondary to Anti-tuberculosis Drug-induced Hepatotoxicity Complication, Its Prevention Strategies and Management: A Case Report

Aim: Tuberculosis remains a public health problem around the world. Hepatotoxicity is a serious side effect of anti-tuberculosis treatment. Fulminant hepatitis is a rare form but considered very serious outside of liver transplantation. It can occur several weeks or months after the start of treatment.
 Presentation of Case: We report the case of a 34-year-old single male patient treated for pleural tuberculosis in whom fulminant hepatitis appeared after four months of treatment with Isoniazid and Rifampicin. Despite a treatment in intensive care unit He had a fatal outcome because of lack of liver transplantation.
 Discussion: Hepatotoxicity varies from biological hepatitis to fulminant hepatitis. Application of personalized strategy of genetic analysis and pharmacological drug monitoring to optimize treatment is the most safe to avoid antituberculosis drug induced hepatotoxicity but not available in all healthcare centers of developing countries. There was any change of anti-tuberculosis protocol because of the risk of bacterial resistance. The protocol includes association between several medicines potentially toxics for a long duration. For some moderate forms of tuberculosis (nodals, pleural), it’s necessary to ask if duration of antiviotherapy can be reduced.
 Conclusion: Prevention of hepatotoxicity starts with identifying risk factors, regular clinical and biological assessment and informing patients of symptom that can indicate toxicity to react early.

Effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis: a systematic review

ObjectivesTo evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis.DesignSystematic review.Data sourcesWe searched in PubMed/MEDLINE, CENTRAL and EMBASE up to 15 January 2023. Additionally,...

Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment-A Study from Patients of Portuguese Health Centers.

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.

Effect of anti-tuberculosis treatment on the systemic levels of tissue inhibitors of metalloproteinases in tuberculosis – Diabetes co-morbidity

ObjectivesTo study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT). MethodsWe examined the levels of TIMP-1, -2, -3 and -4 in pulmonary tuberculosis alone (TB) or TB-DM at baseline and after ATT. ResultsTIMP-1, -3 and -4 were significantly increased in TB-DM compared to TB at baseline and after ATT. ATT resulted in a significant reduction in TIMP-2 and -3 levels and a significant increase in TIMP-1 in both TB and TB-DM. TIMP-1, -3 and -4 were also significantly increased in TB-DM individuals with bilateral, cavitary disease and also exhibited a positive relationship with bacterial burden in TB-DM and HbA1c in all TB individuals. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited higher levels of TIMP-1, -2, -3 and -4 at baseline and TIMP-2 at post-treatment compared to those newly diagnosed with DM (NDM). KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment. ConclusionsTIMP levels were elevated in TB-DM, associated with disease severity and bacterial burden, correlated with HbA1c levels and modulated by duration of DM and metformin treatment.

Effect of anti-tuberculosis treatment on weight of tuberculous patients following up in Gulab Devi Hospital, Lahore

Background: Tuberculosis is the most prevalent disease in Pakistan. Multiple studies have been conducted on disease pattern and anti-tuberculosis therapy however; there is sparse literature of anti-tuberculosis therapy on weight gain of patients. The objective of this study was to measure the effect of anti-tuberculosis treatment on weight of the patient.&#x0D; Subjects and methods: It was a cross sectional study conducted for a period of 1 year at Pulmonology and Surgical OPD of Gulab Devi Chest Hospital Lahore. Interview of 400 patients were recorded and there record of weight and height was collected at start of the treatment, at 02 months and at 6 months of treatment.&#x0D; Results: Mean weight change in 400 patients were 3.06 ± 3.97 Kg. Out of 400 patients 310 had weight gain, 50 patients had weight loss and in 40 patients weight remain unchanged. Mean weight gain in 310 patients was 4.53 ± 2.95 kg with maximum weight gain of 16 Kg. Mean weight loss in 50 patients was 3.67 ± 2.63 Kg with maximum weight loss of 14 Kg.&#x0D; Conclusion: A significant weight gain was seen in patients undergoing anti tuberculosis treatment. Younger age group, treatment completion and drug compliance had positive association with weight gain of the patient. Diabetes mellitus was the only co morbidity found to have negative association with weight gain of the patient.

Adverse drug reactions of anti-tuberculosis treatment among children with tuberculosis.

The frequency, severity, and the nature of anti-tuberculosis (TB)-induced adverse drug reactions (ADRs) have always been the matter of concern. The present study was, therefore, aimed to study the incidence, risk factors, and effect of anti-tuberculosis treatment (ATT) among TB children. A prospective longitudinal study was conducted in the Sindh province, Pakistan. A total of 508 TB children in multicenter hospitals under ATT were assessed for ADRs. Naranjo Causality Assessment and Hartwig's Severity Assessment Scale were used. A total of 105 ADRs were reported in 67 (13.2%) of 508 patients. Gastrointestinal disorders were the most frequently observed ADRs (65.7%), followed by arthralgia (24.8%). Around 65 (61.9%) of ADRs were identified as probable and 78 (74.3%) as mild severe ADRs during the study. A total of four cases of mild hepatotoxicity were observed among children. On multivariate analysis, the independent variables which had statistically significant positive association with ADRs were female (OR; 2.66, P = 0.004), retreatment (OR; 22.32, P = ≤ 0.001), and absence of BCG scar (OR; 17.84, P = 0.001). The finding of the current study suggests that close monitoring of females, patients with previous TB treatment, and those without BCG is warranted at the study site.

Effect of antituberculosis treatment on dynamics of carbohydrate and lipid profile

Objective — study the effect of antituberculosis treatment on the dynamics of carbohydrate and lipid profile in patients with newly diagnosed pulmonary tuberculosisMaterials and methods. We examined 76 patients with drug-susceptible pulmonary tuberculosis and 64 patients with drug-resistant pulmonary tuberculosis. The treatment was carried out according to the current order of the Ministry of Health of Ukraine. Material for the study (venous blood) was collected before treatment and one month later in the morning on an empty stomach. Additionally, an oral glucose tolerance test was performed, the fasting insulin level was determined, the lipid profile was measured, the insulin resistance index (HOMA-IR) and atherogenic index of plasma were calculated. For statistical processing used the software package Statistica for Windows version 13.2.Results and discussion. In the process of treatment with І-line antituberculosis drugs, the level of glucose in 2 hour GTT increased from 4.34 mmol/L to 5. 29 mmol/L. In patients who received ІI-line antituberculosis drugs, the glucose level decreased from 5.77 mmol/L to 4.33 mmol/L, and the fasting insulin level also decreased from 16.30 to 14.47 µcU/mL; the median level of insulin resistance decreased from 3.31 to 2.22 (p = 0.0057). In the process of treatment we found a significant decrease in VLDL levels (р = 0.0028) in drug-susceptible tuberculosis patients. Due to treatment, mean value of HDL-c in in drug-susceptible tuberculosis patients increased slightly from 1.01 mmol/L till 1.12 mmol/L, while in drug-resistant tuberculosis patients it decreased significantly (р=0.0171) from 1.07 mmol/L till 0.94 mmol/L.Conclusions. We found the negative effect of І-line antituberculosis drugs on the carbohydrate metabolism of patients with pulmonary tuberculosis, which manifested as impared glucose tolerance, which makes it possible to recommend OGTT for objectivizing the effect of anti-tuberculosis drugs on carbohydrate metabolism. While in patients who were treated with IІ-line antituberculosis drugs, we found a significant decrease in 2-hour glucose level and fasting insulin level, which indicates the modeling effect of these drugs on carbohydrate metabolism. Our findings suggest that drug-susceptible tuberculosis treatment had a positive effect on the lipid metabolism, which was manifested by the growth of the anti-atherogenic pool of lipoproteins and the decrease in very low-density lipoprotein level. At the same time, we found a negative effect of drug-resistant tuberculosis treatment on lipid metabolism, which manifested as increase of atherogenic index of plasma due to increase of total cholesterol level in patients with newly diagnosed pulmonary tuberculosis.

SURVEY OF ANTITUBERCULOSIS DRUG ADMINISTRATION AND ADVERSE EFFECTS IN ELEPHANTS IN NORTH AMERICA

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease causing morbidity and mortality in captive elephants (Elephas maximus and Loxodonta africana) as well as free-ranging individuals. Elephants in North America diagnosed with tuberculosis are often treated with antituberculosis drugs, unlike livestock species, which has necessitated the development of treatment guidelines adapted from recommendations for humans. There are few published reports describing empirical treatment, which may be complicated by poor patient compliance, interruptions in drug administration, and adverse effects. A survey of elephants in North America was conducted to compile information on treatment protocols, including drugs, dosages, routes of administration, serum drug concentrations, and adverse effects of antituberculosis treatment. Responses were received regarding 182 elephants, 12 of which were treated prophylactically or therapeutically with antituberculosis drugs. Treatment protocols varied among elephants, and included various combinations of isoniazid, rifampin, pyrazinamide, ethambutol, enrofloxacin, levofloxacin, and ethionamide. Serum drug concentrations also varied considerably among and within individuals. Facility staff reported 5 elephants (out of 7 treated elephants with responses) that exhibited clinical signs that may have been associated with antituberculosis drugs or treatment procedures. Anorexia, decreased water intake, constipation, depression, ataxia, limb paresis, and tremors were among the signs observed. Most adverse effects were reported to be moderate or severe, resulting in interruption of the treatment. The results from this survey provide veterinarians and elephant managers with valuable historical data to make informed clinical management decisions regarding antituberculosis therapy in elephants.

Effect of anti-tuberculosis treatment on thyroid profile in newly detected smear positive pulmonary tuberculosis cases

Background: Tuberculosis being a systemic disease and has a capacity for wide spread dissemination. Present study aims to identify the effects of antituberculous treatment on thyroid profile in new smear positive pulmonary tuberculosis cases.Methods: This study was conducted among 60 new smear positive pulmonary tuberculosis cases attending pulmonary medicine OPD from May 2015 to April 2017. Thyroid function test in the form of free T3, free T4 and TSH was measured before initiating Anti tuberculosis treatment (ATT), at 3 months and at the end of 6 months.Results: Out of 60 patients enrolled in present study, majority were males. Diabetes mellitus was the major co morbidity. Sick euthyroid was found to have decreasing trend during the course of treatment, and hypothyroidism was found to be increasing trend end of 6 months.Conclusions: The common Thyroid Dysfunction seen during the study period was Hypothyroidism and Sick euthyroid. Anti-tuberculous medication preferably Rifampicin probably would explain the cause for these thyroid dysfunctions noticed during the study time. And those patients with significant hypothyroid need to started on thyroid supplements. Among the drugs used for treatment, rifampicin was probably the cause for thyroid dysfunction noticed during the course of treatment. Hence, authors recommend that these patients should be started on thyroid supplements after the diagnosis of significant hypothyroidism.

Addressing the tuberculosis-depression syndemic to end the tuberculosis epidemic.

Tuberculosis (TB) and depression act synergistically via social, behavioral, and biological mechanisms to magnify the burden of disease. Clinical depression is a common, under-recognized, yet treatable condition that, if comorbid with TB, is associated with increased morbidity, mortality, community TB transmission, and drug resistance. Depression may increase risk of TB reactivation, contribute to disease progression, and/or inhibit the physiological response to anti-tuberculosis treatment because of poverty, undernutrition, immunosuppression, and/or negative coping behaviors, including substance abuse. Tuberculous infection and/or disease reactivation may precipitate depression as a result of the inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Clinical depression may also be triggered by TB-related stigma, exacerbating other underlying social vulnerabilities, and/or may be attributed to the side effects of anti-tuberculosis treatment. Depression may negatively impact health behaviors such as diet, health care seeking, medication adherence, and/or treatment completion, posing a significant challenge for global TB elimination. As several of the core symptoms of TB and depression overlap, depression often goes unrecognized in individuals with active TB, or is dismissed as a normative reaction to situational stress. We used evidence to reframe TB and depression comorbidity as the 'TB-depression syndemic', and identified critical research gaps to further elucidate the underlying mechanisms. The World Health Organization's Global End TB Strategy calls for integrated patient-centered care and prevention linked to social protection and innovative research. It will require multidisciplinary approaches that consider conditions such as TB and depression together, rather than as separate problems and diseases, to end the global TB epidemic.

Effect of antituberculosis treatment on CYP2C19 enzyme activity in genetically polymorphic South Indian Tamilian population.

Patients on antituberculosis therapy (ATT) are more prone to drug interactions in the presence of coexisting illnesses which require drug therapy. Rifampicin is a pleiotropic inducer of CYP enzymes, and isoniazid is an enzyme inhibitor. Genetic variations are common in the gene coding for CYP2C19 enzyme. These variations would be important in predicting the individual variations in CYP2C19 activity. The objectives of the study were to find the net effect of 1-month ATT on CYP2C19 enzyme activity and its association with CYP2C19 genetic polymorphisms. Newly diagnosed tuberculosis patients (n = 125) were included in the study. Before commencing ATT, they were given a single dose of omeprazole 20 mg as a probe drug for CYP2C19. Blood sample was collected after 3 h to carry out phenotyping for CYP2C19 enzyme by measuring omeprazole hydroxylation index (OHI) using LC-MS/MS. The phenotyping procedure was repeated after 1 month of ATT. CYP2C19 genotyping was carried out by PCR-RFLP method. Significant reduction in OHI was observed after 1 month of ATT in all the metabolizer groups. The percentage reduction in OHI was maximum with poor metabolizers, 84.1 (IQR - 74.6, 86.6), and minimum with ultra-rapid metabolizers, 39.6 (IQR - 12.7, 54.7). CYP2C19 enzyme induction is predominant in patients after 1 month of antituberculosis treatment (ATT). Genetic variations in the enzyme could not clearly explain the interindividual differences in induction. There is a potential risk of drug failure/adverse effect in poor metabolizers regardless of their genotype after ATT.

Effect of standard tuberculosis treatment on naive, memory and regulatory T-cell homeostasis in tuberculosis-diabetes co-morbidity.

Perturbations in CD4(+) and CD8(+) T-cell phenotype and function are hallmarks of tuberculosis-diabetes co-morbidity. However, their contribution to the pathogenesis of this co-morbidity and the effect of anti-tuberculosis treatment on the phenotype of the T-cell subsets is poorly understood. In this study, we examined the frequency of different T-cell subsets in individuals with pulmonary tuberculosis (PTB) with diabetes mellitus (DM) or without coincident diabetes mellitus (NDM) before, during and after completion of anti-tuberculosis chemotherapy. PTB-DM is characterized by heightened frequencies of central memory CD4(+) and CD8(+) T cells and diminished frequencies of naive, effector memory and/or effector CD4(+) and CD8(+) T cells at baseline and after 2months of treatment but not following treatment completion in comparison with PTB-NDM. Central memory CD4(+) and CD8(+) T-cell frequencies exhibited a positive correlation with fasting blood glucose and glycated haemoglobin A1c levels, whereas the frequencies of naive and effector memory or effector CD4(+) and CD8(+) T cells exhibited a negative correlation. However, the frequencies of CD4(+) and CD8(+) T-cell subsets in individuals with PTB exhibited no significant relationship with bacterial burdens. Finally, although minor alterations in the T-cell subset compartment were observed at 2months of treatment, significantly decreased frequencies of central memory and significantly enhanced frequencies of naive CD4(+) and CD8(+) T cells were observed at the completion of treatment. Our data reveal a profound effect of coexistent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy.

The effect of antituberculosis treatment on interferon-γ release assay results

Monitoring the efficacy of antituberculosis therapy is crucial. The aim of this work is to investigate the effect of tuberculosis treatment on interferon-gamma response using Quanti-FERON-TB Gold in tube (QFT-GIT). A total of 216 new pulmonary tuberculosis (TB) cases were tested with QFT-GIT at the start of the treatment and, randomly, once or twice between 90 and 180 days afterwards. Data was analysed using the random effect regression model analysis. 63.4% of patients were positive at the QFT-GIT (> .35 UI cut-off). TB cases showed a significant log-linear increase in interferon-gamma (IFN-gamma) concentration, over time of treatment: IFN-gamma concentration increased by 78% after 6 months of treatment in acid-fast bacilli positive (A) and culture negative cases in culture confirmed cases the increase was 43% if A+ and 20% in A-. Effective therapy seems to restore cellular responses to Mycobacterium tuberculosis antigens. The potential use of interferon gamma release assay (IGRA) in monitoring response to TB treatment is hampered by the presence of active mycobacterial replication at baseline and needs further evaluation.

Effect of anti-tuberculosis treatment in tuberculosis patients co-infected with human immunodeficiency virus in seven counties,Yunnan

To understand the potential risk factors influencing the effect of standard anti-tuberculosis (TB) treatment for TB patients co-infected with human immunodeficiency virus (HIV) and provide evidence for the improvement of anti TB therapy. A retrospective study was conducted among 445 TB/HIV patients diagnosed and registered in 7 counties in Yunnan province from January 2010 to June 2012. A structured questionnaire was used to collect the patients' demographic characteristics, diagnosis and treatment information after informed consent. Chi-square test was conducted to compare successful rate of anti TB treatment among the patients with different demographic characteristics. Multivariate logistic regression analysis was conducted to identify risk factors influencing the effect of anti TB treatment. Adjusted OR>1 means the risk factor of treatment failure. P value less than 0.05 was set as significant level. After standard anti TB treatment, 397 patients were cured. The five risk factors influencing treatment effect were the existing of 4 suspected TB symptoms when seeking medical care for the first time (adjusted OR = 2.208), TB/HIV patients detected in HIV/AIDS screening (adjusted OR = 5.856), severe case (adjusted OR = 4.607), non-full-course supervision during treatment (in intensive phase adjusted OR = 4.129, full-course management adjusted OR = 8.090) and interruption of therapy (adjusted OR = 21.517). Early detection of TB/HIV patients and conducting full course supervision during treatment can improve the effect of anti TB treatment. It is necessary to strengthen the early detection of TB/HIV patients and standarded treatment in Yunnan province.

Characteristics of tuberculosis in patients with rheumatoid arthritis: a retrospective single-center study.

The objective of this study was to assess the characteristics of hospitalized patients suffering from tuberculosis with rheumatoid arthritis (RA), focusing specifically on those treated without anti-tumor necrosis factor (TNF) therapy. We conducted a retrospective review to assess the characteristics of 1,022 hospitalized Japanese patients suffering from tuberculosis with and without RA between 2002 and 2011. Compared with the 995 non-RA patients with tuberculosis, the 24 RA patients with tuberculosis treated without anti-TNF therapy were older and predominantly female. They less frequently had a history of smoking, with a higher rate of underlying respiratory diseases, an impaired performance status and side effects. The three RA patients receiving anti-TNF therapy had extrapulmonary tuberculosis; however, the rate of extrapulmonary tuberculosis in the other RA patients treated without anti-TNF therapy did not differ from that observed in the non-RA patients. Five patients died during hospitalization. The in-hospital mortality of the RA patients did not differ significantly from that of the non-RA patients. Independent factors contributing to in-hospital mortality did not include RA. In this study, the RA patients treated without anti-TNF therapy did not differ from the non-RA patients in terms of the rate of extrapulmonary tuberculosis or bilateral pulmonary lesions, although they did exhibit a higher frequency of side effects of antituberculosis treatment. RA was not found to be an independent factor contributing to in-hospital mortality.

N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians

Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients. Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol-chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant. This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

Effect of Antituberculosis Treatment on Serum Zinc Level in Tuberculosis

INTRODUCTION: Tuberculosis is a major public health problem worldwide. One third population of world is infected with M. tuberculosis. Zinc is micro-mineral essential for human growth, development and immune function. Deficiency of this micronutrient impairs overall immune function and resistance to infection. Present study was conducted to evaluate the level of serum zinc in patients with tuberculosis at various period of treatment. METHODS: Total 92 subjects included were evaluated from OPD, IPD and DOTS centre of MGM group of Hospitals, Navi Mumbai, India. Among them there were 50 patients with Tuberculosis and 42 normal healthy controls. In all the subject estimation of Zinc was carried out. Out of 50 tuberculosis patients, 31 patients were assessed for zinc after two months and six months (i.e. completion) of DOTS therapy. The assessment was done according to the cut off values of serum zinc i.e. 60- 120 µgm/dl. RESULTS: Serum zinc levels were significantly low (p&lt;0.001) in study group as compared to the healthy control. Serum zinc concentration of the patients increased gradually after anti-tuberculous therapy and reached normal levels after completion of therapy. CONCLUSION: In the present study serum zinc levels of patients with pulmonary tuberculosis was found low as compared to healthy control subjects. Supplement of zinc during the treatment can be important for the betterment of the treatment of this disease. DOI: http://dx.doi.org/10.3126/jucms.v1i3.8751 Journal of Universal College of Medical Sciences Vol.1(3) 2013: 15-17

Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced hepatotoxicity patients.

Hepatotoxicity is a serious adverse effect of antituberculosis treatment (ATT). Glutathione S-transferase (GST) is involved in the detoxification of toxic metabolites produced as a result of ATT, increased oxidative stress and decreased antioxidant levels, and differences in the GST polymorphism may be one of the causes of ATT-induced hepatotoxicity. This study was undertaken to study the relationship among antioxidant status, oxidative stress and GST gene polymorphisms in the development of ATT-induced hepatotoxicity in Indian patients. Two hundred fifty TB patients attending clinics in the Gastroenterology and Thoracic Department, PGIMER, Chandigarh, were enrolled. Liver marker enzymes, markers of oxidative stress, levels of antioxidants and identification of GSTT1, GSTM1 and GSTP polymorphisms were performed using standard protocols. Of the 250 patients, 160 were males. Of the 160 males, 18 (11.3%) had ATT-induced hepatotoxicity and 142 no hepatotoxicity, while of 90 females, 12 (13.3%) had hepatotoxicity and 78 no hepatotoxicity. Patients who developed ATT-induced hepatotoxicity had significantly higher oxidative stress compared to those who did not develop hepatotoxicity at between 1 and 2months of treatment. Among antioxidants, catalase did not show any significant difference at 2 and 4months of treatment. The presence of GSTM1 was higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, while GSTT1 and GST1/M1 were lower. Therefore, in this study, the possible association of oxidative stress with ATT-induced hepatotoxicity was observed. A role of the GST polymorphism in ATT-induced hepatotoxicity was also found and thus could possibly identify the groups at highest risk of developing ATT-induced hepatotoxicity.

Effect of honey on hepatotoxicity induced by antitubercular drugs in albino rats

Background: Drug-induced hepatotoxicity is a potentially serious adverse effect of antituberculosis treatment (ATT) regimens containing isoniazid, rifampicin and pyrazinamide. Many in vitro and in vivo studies revealed that honey possess antioxidant property and hepotoprotective property but there is no systematic work available to test the effect of honey on antitubercular drugs induced hepatotoxicity in rats. Hence present study was carried out to explore the prophylactic and therapeutic effect of honey with its antioxidant activity against hepatotoxicity induced by antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) in albino rats. Methods: Hepatotoxicity in rats treated with antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) was studied by assessing parameters such as Serum alanine aminotransferase (ALT), Serum aspartate aminotransferase (AST), Serum total protein, Serum Malondialdehyde (MDA) and Serum Superoxide dismutase activity (SOD). The effect of Honey as co-administration and administration after establishment of hepatotoxicity on above parameter was investigated. These biochemical observations were supplemented by Histopathological examination of liver. Results: Honey significantly reversed changes in serum levels of AST, ALT, MDA, SOD, total protein and also histopathological changes produced by Antitubercular drugs. It was found that honey significantly prevented as well as reversed Antitubercular drugs induced hepatotoxicity and antioxidant activity. Conclusions: The results of present study show that honey has significant prophylactic and therapeutic value against antitubercular drugs induced hepatotoxicity.

The effect of anti-tuberculosis treatment on levels of anti-phospholipid and anti-neutrophil cytoplasmatic antibodies in patients with active tuberculosis

The aim of this study is to determine the prevalence and effect of anti-tuberculosis treatment on anti-phospholipid antibodies and anti-neutrophil cytoplasmatic antibodies (ANCA) in patients with active mycobacterial infections. Thirty-three consecutive patients (age 56 years, 26 males) with recently diagnosed active tuberculosis (TB) were enrolled. Data included clinical disease features, symptom duration, multidrug resistance and presence of HIV. Serum samples taken before and after TB treatment were frozen at -20 °C and tested for anti-cardiolipin IgG (aCL), anti-β2 glycoprotein IgG (anti-β2GPI), anti-prothrombin, anti-proteinase 3 (PR3), myeloperoxidase (MPO), bactericidal/permeability (BPI) and lactoferrin. Thirty percent of patients had higher than cut-off value for anti-β2GPI, and 9 % had increased aCL. The levels of antibodies against β2GPI and aCL normalized post-treatment. A substantial proportion of patients had high baseline anti-PR3, MPO, BPI and lactoferrin levels. Most anti-lactoferrin and anti-MPO levels decreased post-treatment, while anti-PR3 increased in most of the baseline-positive patients. Some patients had de novo anti-PR3 and MPO formation after 6-month treatment. Patients with active TB have significantly increased anti-β2GPI and ANCA titers. While anti-β2GPI titers normalize post-treatment, ANCA behave in a complex way. Anti-TB treatment may induce normalization of anti-lactoferrin and anti-MPO, and de novo anti-PR3 and MPO formation.