Druginduced hepati tis, hcpatic drug metabolism, idiosyncrat ic hepalotoxim isoniazid. Until recently it was thought that age greater than 35 yr was the main risk factor for the development of druginduced hepatitis dih in patients. These include patients with preexisting liver diseases, particularly those associated with chronic viral infection due to hepatitis b, hepatitis c, and hiv, the alcoholics, the elderly and the malnourished. Drug induced hepatotoxicity of antituberculosis drugs and their. In this case, the patient was receiving antitubercular drugs. The clinical impact of druginduced hepatotoxicity on anti. Risk factors associated with this potentially fatal complication include coinfection with hiv, hepatitis b or c, preexisting chronic liver disease, high alcohol intake, malnutrition.
Donald department of paediatrics and child health, faculty of health sciences, university of stellenbosch and tygerberg childrens hospital, tygerberg, south africa abstract recent increases in the dosages of the essential antituberculosis agents isoniazid. The incidence of antitb drug induced hepatotoxicity varies widely. Ungo jr, jones d, ashkin d, hollender es, bernstein d, albanese ap, pitchenik ae. Antituberculosis druginduced hepatotoxicity is quite common. The risk of antitb drug induced hepatotoxicity is higher in patients with chronic hepatitis b virus hbv patients compared to uninfected subjects 16% vs 4. Statistical analysis was done by applying students ttest for continuous variables and chisquare test with yates correction for dichotomous variables. Viral hepatitis viral hepatitis is a systemic infection affecting primarily the livert. Antituberculosis druginduced hepatotoxicity in children. Risk factors hepatotoxicity antituberculosis drugs. The incidence of drug induced hepatitis is high at doses of 4070 mgkg per day but. Antituberculosis druginduced hepatotoxicity the role of. Polymorphism of the nacetyltransferase 2 gene as a susceptibility risk factor for antituberculosis druginduced hepatitis. Antituberculosis drug induced hepatitis a case report.
Its major influence is on the important cause of liver injury. Firstline antitb drugs associated with hepatotoxicity are isoniazid inh, rifampicin rif and pyrazinamide pza. All patients diagnosed with active tb and being treated at a. Druginduced hepatotoxicity dih is the most common adverse drug reaction leading to interruption of antituberculosis treatment. The risk of antituberculosis tb druginduced liver injury dili in patients with chronic viral hepatitis. Indian journal of pharmacy practice volume 6 issue 2 apr jun, 20 67 amer k antituberculosis drug induced hepatitis a case report. Prevalence of hepatotoxicity from antituberculosis therapy. Antituberculosis att druginduced liver injury dili is a common and serious adverse effect of tuberculosis tb treatment.
Transporters, enzymes, and excretion drug induced liver injury. Genetic polymorphisms of drugmetabolizing enzymes and the susceptibility to antituberculosis druginduced liver injury. Cytochrome p450 2e1 genotype and the susceptibility to antituberculosis druginduced hepatitis. Drug induced hepatitis with antitubercular chemotherapy. The aim of this retrospective study was to find out whether chronic viral hepatitis affects the incidence and onset time of dih. Druginduced liver injury dili is a wellrecognised adverse drug reaction of tb treatment and art. Druginduced hepatotoxicity was defined when liver transaminase levels exceeded. In a single center registry of 303 patients from bangalore, antituberculosis drugs contributed to 58% cases of dili16. Toxic hepatitis is the most severe adverse reaction to antituberculosis drugs. The use of levofloxacin after hepatitis induced by antituberculosis drugs produced no additional hepatotoxicity.
Analysis of il6, stat3 and hspa1l gene polymorphisms in. Drug induced liver injury dili is a wellrecognised adverse drug reaction of tb treatment and art. Druginduced hepatotoxicity of antituberculosis drugs and. However, factors predicting its development are still controversial.
Antituberculosis drugs and hepatotoxicity wiley online library. Drug induced hepati tis, hcpatic drug metabolism, idiosyncrat ic hepalotoxim isoniazid. The published data support the safety of levofloxacin use in tuberculosis treatment and even after firstline antituberculosis druginduced hepatitis. Antituberculosis drugs and hepatotoxicity yew 2006. It usually installs in the first few weeks of treatment, in parallel with liver necrosis, which may evolve to encephalopathy and death. In a standard fourdrug regimen, pza was the most common cause of druginduced hepatitis and was doserelated. Ethambutol emb can be used safely in patients with hepatic disease. Inactive hepatitis b surface antigen carrier state and. Download pdf bmc infectious diseases biomed central. Singh, arora, garg, thakur, pande, tandon patients with attinduced hepatitis. Until recently it was thought that age greater than 35 yr was the main risk factor for the development of druginduced hepatitis dih in patients receiving antituberculosis therapy.
Challenges and difficulties in treatment, kathmandu university medical journal 2007, vol. Although the guidelines for the management of antituberculosis drug induced hepatitis have been published from varieties of health institutes and organizations, they are to a great extent highly similar, there are nevertheless some important differences. This retrospective study was carried out to study the prevalence of dili among patients who had received antitb medications and to study some of the known risk factors responsible for causing dili. Antituberculosis drugs among patients treated for active tuberculosis, american journal of respiratory and critical care medicine, vol 167 2003. Biochemical tests of hepatocellular injury were repeated every week till recovery in patients withattinducedhepatitis. We aimed to determine the incidence and risk factors of atli in children during the first 2 months of tb therapy methods. Sterling, on behalf of the ats hepatotoxicity of antituberculosis therapy subcommittee this of. Frequency of first line antituberculosis drug induced. The objective of the present study was to evaluate the role of certain factors age and sex of the patient, alcoholism, chronic liver disease, hepatitis b virus carrier status, acetylator status, nutritional status and antituberculosis. Worldwide, different reintroduction regimens have been advocated, but no consensus guidelines are available. Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death. More than 900 drugs, toxins, and herbs have been reported to cause liver injury.
The risk factors most frequently associated with druginduced hepatitis are. Patients with human immunodeficiency virus coinfection, acute viral hepatitis, chronic liver disease, suspicious malabsorption gastrointestinal disease, diarrhea. Antituberculosis druginduced liver injury in children. Hepatotoxicity of antituberculosis therapy american thoracic society. Vaghela1 vivek nimbark2 manish barvaliya1 hita mehta2 bhavesh chavada3 published online. Many of the commonly used antitb drugs are associated with significant potential of causing hepatotoxicity. Resistant strains emerge quickly if this drug is used on its own so it is best used in combination with other antituberculosis medicines. Challenges and difficulties in treatment, kathmandu. Recurrent druginduced hepatitis in tuberculosiscomparison of two. Druginduced hepatitis, from tb treatment, has a mortality rate of around 5%. While the occurrence of drug induced hepatitis is difficult to predict, it has been observed that certain patients are at higher risk of developing drug induced hepatitis during the course of antitb chemotherapy. Isoniazid, rifampicin and pyrazinamide are all associated with hepatitis. Druginduced liver injury dili secondary to antituberculous treatment att is reported in 228% of patients 1, 2 varying with the definition, study population and treatment regimen. There is currently no way to reimburse for the absence of liver function.
At least 8 different types of viruses directly associated with vi ral hepatitis have been identified. Acetaminopheninduced hepatic injury is the most common form of druginduced liver disease and more particularly of acute liver failure in the united states, accounting for nearly 50% of all cases. As one of the most frequent and serious adverse reactions during tuberculosis tb treatment, antituberculosis druginduced liver injury atli in children has been studied insufficiently compared with adults. Single center registries of dili continue to highlight the high incidence of dili and dialf, much of it due to diagnostic errors and inappropriate prescriptions. Antituberculosis druginduced hepatotoxicity the role of hepatitis.
Huang ys, chern hd, su wj, wu jc, lai sl, yang sy, et al. Antituberculosis druginduced liver injury with autoimmune. Druginduced liver injury from antituberculous treatment. Antituberculosis druginduced liver injury tb dili is a leading cause of dili and druginduced acute liver failure dialf in india and much of the developing world. We conducted a study to determine whether infection with either the hepatitis c virus or the human immunodeficiency virus hiv were significant risk factors for. In addition, only one study 14 x 14 ungo, jr, jones, d, ashkin, d et al. Antituberculosis druginduced hepatitis has also been found to be associated with acetylator phenotypes and other genetic polymorphisms, including cytochrome p450 2e1 and glutathione stransferase m1, and certain major histocompatibility complex class ii associated hladq alleles. Hepatitis c virus infection and hepatotoxicity during.
The incidence rate of antitb induced hepatotoxicity is found to be 2% to 28%. Hepatitis monthly epsteinbarr virus infection mimicking. The authors present a case report of antituberculosis druginduced liver injury that offered diagnostic challenges namely, the possibility of druginduced autoimmune hepatitis and treatment difficulties. Drug interactions, adverse effects, and use in special situations. In addition to common types of viral hepatitis, ie, hepatitis a, hepatitis b, and hepatitis c viruses, epsteinbarr virus ebv may result in hepatitis in some cases. Antituberculosis druginduced hepatotoxicity in children peter r.
Although hepatitis is frequently observed during antituberculosis antitb therapy, acute viral hepatitis should be ruled out first, especially in the endemic areas. Various types of drug induced liver diseases are acutedose dependent hepatitis, liver cirrhosis, liver tumors etc. Risk factors clinical risk factors for druginduced hepatotoxicity. Whether antituberculosis antitb treatment in patients with chronic viral hepatitis affects the incidence and onset time of druginduced hepatotoxicity dih is still controversial. Antituberculosis treatment and hepatotoxicity in patients. Whether chronic viral hepatitis due to hepatitis b virus and hepatitis c virus increases the risk of. Of the 93 patients who were given at least one hepatotoxic antitb drug in the initial regimen, 18 19. The drug most frequently implicated as causing a drug fever is rmp. In a standard four drug regimen, pza was the most common cause of drug induced hepatitis and was doserelated. Antituberculosis druginduced liver injury in chronic. There are limited data available on whether druginduced hepatotoxicity.
Antituberculosis druginduced hepatitis is one of the most prevalent druginduced liver injuries in taiwan and many other countries. Hepatotoxicity is a major sideeffect of the medicines used in tuberculosis therapy. Knowledge of the metabolism of antitb medications and of the mechanisms of tb. Cytochrome p450 2e1 genotype and the susceptibility to. Reintroduction of antituberculosis drugs in patients with dih has never been studied. Although the guidelines for the management of antituberculosis drug induced hepatitis have been published from. Pharmacogenetic study of drugmetabolising enzyme polymorphisms on the risk of antituberculosis druginduced liver injury. Dili complicates tb treatment in 5 33% of patients. Diagnosis of druginduced hepatitis the diagnostic criteria for druginduced hepatitis were as follows. Against tuberculosis and lung disease guidelines have some minor variations. Ungo jr, jones d, ashkin d, hollender es, bernstein d, albanese ap, et al. Antituberculosis therapy in patients with hepatitis b.
Druginduced liver injury dili is a problem of increasing signifi cance, but has. Pdf cytochrome p450 2e1 genotype and the susceptibility. The role of hepatitis c virus and the human immunodeficiency virus. Frequency of first line antituberculosis drug induced hepatitis 7 discussion att induced hepatitis is one of the most important side effects as it can force the physician to modify the treatment to drugs which are less effective and also have more side effects, or it may lead to overt fulminant hepatitis which may endanger the life. Pdf antituberculosis druginduced hepatitisa case report.