Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects

Anti-tuberculosis Drug- flummoxd Liver Injury (ATLI) EffectsAbstractTuberculosis (TB) is worlds deadliest communicable disease, with 9 million incident cases and 1.5 million deaths globally in 2013. Most of the cases of TB were reported from Asian (56%), and African (29%) continents. In Saudi Arabia the annual relative incidence enjoin of TB ranged between 14 and 17/100,000. Two provinces, Makkah and Jazan showed the highest incidence around 20/100,000 over the last one decade. Jazan region showed more than double the incidence rate of TB compared to embossment of the Southern province. Jazan share border with Yemen, and receives many illegal immigrants. Studies showed that non-Saudi Arabians had 2-3 times higher incidence of TB than Saudi national. The large human body of Non-Saudis came from countries with high incidence of TB such as Bangladesh, Pakistan, India, Indonesia, Philippines, Yemen, Ethiopia, Somalia, Chad, Nigeria and other African countries. The active TB patients can be treated safely and effectively by dint of the directly-observed therapy strategy (DOTS). DOTS is a short course of standard anti-TB treatment which consist of taking drug combinations of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol and Streptomycin for 69 months. The drug isoniazid, rifampicin and pyrazinamide have the potential to induce coloured damage.This anti-tuberculosis drug-induced liver injury (ATLI) ranges from mild to severe forms, and can even be fatal. The incidence of ATLI during standard anti-TB treatment range from 2.0% to 28.0% according to different populations. Moreover, ATLI conquer the talent of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly muffle the effects of TB control. To the best of our knowledge, there is no know promulgated data on the incidence of anti-tuberculosis drug-induced liver injury (ATLI) and risk factors from Saudi population. Identification of patients at attach d risk for ATLI is important because hepatotoxicity causes significant morbidity and deathrate and may require modification of the therapeutic regimen. The aim of this study will to estimation the incidence of ATLI and the risk factors associated with anti-TB treatment. The findings of this study will allow us to enkindle TB treatment, monitoring and control of the TB in KSA.IntroductionTuberculosis (TB) is worlds deadliest communicable disease, with 9 million incident cases and 1.5 million deaths globally in 2013 1. Most of the cases of TB were reported from Asian (56%), and African (29%) continents 1. In Saudi Arabia the annual incidence rate of TB ranged between 14 and 17/100,000 2. Two provinces, Makkah and Jazan showed the highest incidence around 20/100,000 over the last one decade 2. Jazan region showed more than double the incidence rate of TB compared to rest of the Southern province. Jazan share border with Yemen, and receives many illegal immigrants. Studies showed that non-Saudi Arabians had 2-3 times higher incidence of TB than Saudi national. 3.The large number of Non-Saudis came from countries with high incidence of TB such as Bangladesh, Pakistan, India, Indonesia, Philippines, Yemen, Ethiopia, Somalia, Chad, Nigeria and other African countries. Patients with active TB disease can be treated safely and effectively through the directly-observed therapy strategy (DOTS) which started in 2000. DOTS is a short course of standard anti-TB treatment which consist of taking drug combinations of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol and Streptomycin for 69 months 4. These drugs effectively kills the bacteria but it induced hepatotoxicity cognise as anti-tuberculosis drug-induced liver injury (ATLI) 5.tostmann 2008.The ATLI ranges from mild to severe forms, and can even be fatal. The incidence of ATLI during standard anti-TB treatment range from 2.0% to 28.0% according to different populations. 5,6. The incidence is higher in the developing c ountries (8% to 39%), compared to developed countries (3%4%) (7-11). Moreover, ATLI reduce the efficacy of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly reduce the effects of TB control. 5,6.Many risk factors have been regard for ATLI. These accommodate older age, female gender, poor nutritional status, pre-existing liver disease, high intoxicant intake, hepatitis B, malnutrition, hypoalbuminaemia and advanced TB (12-16). Inappropriate use of drugs, acetylator status, and recently, immunogenetic factor, have also been implicated (17,18). Infections with hepatitis C virus and human immunodeficiency virus (HIV) have also been said to increase the risk (19).It is very important to understand the risk factors of ATLI, in order to detect the adverse events earlier and deliver timely intervention. The identification of high-risk patients would be useful to allow early detection of hepatotoxicity and reduce the morbidity an d mortality of this condition. Hence we plan this study to identify the risk factors associated with anti-tuberculosis drug induced liver injury in patients who receive anti-TB treatment. To the best of our knowledge, there is no known published data on the incidence of anti-tuberculosis drug-induced liver injury (ATLI) and risk factors from Saudi population. The aim of this study will to estimate the incidence of ATLI and the risk factors associated with anti-TB treatment. The findings of this study will allow us to enhance TB treatment, monitoring and control of the TB in KSA.2. PROJECT OBJECTIVESThis study aimed to estimate the incidence and risk factors of anti-tuberculosis Drug Induced Liver Injury (ATLI) in patient receiving anti-TB treatment in Jazan population.1. To estimate the incidence of abnormal liver function tests (LFTs) in patient receiving anti-TB treatment.2. To identify the risk factors associated with anti-tuberculosis Drug Induced Liver Injury (ATLI) in patient receiving anti-TB treatment. check of LiteratureIncidenceThe first line drugs used to treat TB were isoniazid (INH), rifampicin (RIF), pyrazinamide (PZY) and ethambutol (EMB). Most of the TB patients tolerate the drugs but some develop hepatotoxicity known as anti-tuberculosis drug-induced liver injury (ATLI). Forget 2006.The ATLI ranges from mild to severe forms, and can even be fatal. Data from the literature shows that the incidence of ATLI is 3.0% in Canada (Asia population accounted for 42%)Yee 2003, mainland China 2.5% Shang 2011, 5.0% in Hong Kong Chang 2008, 5.3% in Singaporeteleman 2002, 16.1% in Taiwan Huang 2003, 9.7% in Malaysia Marzuki 2008,36% in Japan Ellard 1978, 8-36 per cent in India Parthasarthy 1986, Mehta 1990, 13% Iran Baghaei. The risk of developing ATLI was fivefold for hepatitis C patients, multiple for HIV positive patients, and 14 fold for patients co-infected with hepatitis C and HIV Ungo 1998.The incidence is higher in the developing countries (8% to 39 %), compared to developed countries (3%4%) (7-11). Moreover, ATLI reduce the efficacy of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly reduce the effects of TB control. 5,6.Definition of ATLIThe criteria for the diagnosis of ATLI in the absence of symptoms is elevation of transaminases up to 5 times the upper limit of normal (ULN) and in the presence of symptoms up to three times the ULN or twice the ULN of bilirubin in the seam Saukkonen 2006.Mechanism of toxicityAmong Isoniazid, rifampicin, pyrazinamide and ethambutol, the first three drugs have the potential for hepatotoxicity with pyrazinamide (PZA) being the most hepatotoxic followed by isoniazid (INH) and rifampicin.YeeRifampicin combined with PZA is more hepatotoxic than with INH. Jasmer 2002Pyrazinamide contributes significantly to acute liver failure Durand 1995.The most important adverse effects of isoniazid are hepatic toxicity and potentially fatal drug-in duced hepatitisNolan 1999, especially when associated with rifampicin. The relative frequency of occurrence of isoniazid-associated hepatitis depends on age. Other factors linked to a predisposition to isoniazid-associated hepatotoxicity include alcohol abuse, use of illegal drugs and a previous history of liver disease.clinical featuresATLI usually take place in the first 2 months of treatment but it may happen at any time during the treatment period. clinical and biochemical features of ATLI are difficult to differentiate form viral hepatitis Mitchell 1976. The signs and symptoms of ATLI are jaundice, abdominal pain, nausea, vomiting and Weakness.Risk factors for ATLIMany risk factors have been implicated for ATLI. These include older age, female gender, poor nutritional status, pre-existing liver disease, high alcohol intake, hepatitis B, malnutrition, hypoalbuminaemia and advanced TB (12-16). Inappropriate use of drugs, acetylator status, and recently, immunogenetic factor, hav e also been implicated (17,18). Infections with hepatitis C virus and human immunodeficiency virus (HIV) have also been said to increase the risk (19).