Inh and rif induced hepatotoxicity has been studied using rodent models, the most important being wistar albino rats. Although these hla associations have contributed to our understanding of the immunopathogenesis of dili, the very poor positive. Protective effects of quercetin against isoniazid and rifampicin induced hepatotoxicity in rats article pdf available july 2014 with 493 reads how we measure reads. In this case, the patient was receiving antitubercular drugs from 3 months and developed hepatitis which is a severe adverse drug reaction. Transporters, enzymes, and excretion drug induced liver injury. Drug induced hepatotoxicity of antituberculosis drugs and their serum levels the correlation between serum antituberculosis tb drug levels and the drug induced hepatotoxicity dih remains unclear. Inhibition of isoniazidinduced hepatotoxicity in rabbits by. We describe druginduced liver injury dili secondary to antituberculous treatment att in a large tuberculosis tb centre in london. She was admitted to the hospital for epigastric and right sided flank pain of oneweek duration. Pdf cyp2e1 genotype and isoniazidinduced hepatotoxicity. Drug induced liver injury covers a variety of types, and includes most of the clinical and pathological expressions of liver damage 6. Isoniazid, rifampicin, gsp method, mannitol, tuberculosis, hepatotoxicity. The injury may suggest a hepatocellular injury, with elevation of aminotransferase levels as the predominant symptom, or a cholestatic injury, with elevated alkaline phosphatase levels with.
Drug hepatotoxicity, is the leading cause of acute liver failure alf. We identified consecutive patients who developed dili whilst on treatment for active tb. Of the 17 patients with hepatotoxicity by definition iii, 3 presented no side effects and treatment was well tolerated. Druginduced hepatotoxicity of antituberculosis drugs and their serum levels the correlation between serum antituberculosis tb drug levels and the druginduced hepatotoxicity dih remains unclear. Its major influence is on the important cause of liver injury. Druginduced alf is also associated with high morbidity and mortality, only a 20% survival in the absence of liver transplantation. Treatment of isoniazid induced hepatotoxicity as regards the treatment of inh induced hepatotoxicity, it presents a difficult challenge to manage due to a number of factors such as, patients affected are often on other potentially hepatotoxic drugs, making it more. Drug induced alf is also associated with high morbidity and mortality, only a 20% survival in the absence of liver transplantation. Induced by rifampicin hydrazine conjugation isonicotinyl glycine diacetyl hydrazine figure 2 rifampicin induction ofthe hydrolysispathwayofisoniazid metabolism into the hepatotoxic metabolite hydrazine. Isoniazid metabolism and hepatotoxicity sciencedirect. The pattern of hepatotoxicity observed during therapy with the vasodilator. In the usphs study 63, there were 8 deaths among,838 enrolled subjects 0.
Diagnosis, management and prevention of druginduced liver. Cytochrome p450 2e1 cyp2e1 is thought to contribute to the synergistic effects of rif and inh. Inh has since been associated with two syndromes of hepatotoxicity. Dili has become the leading cause of acute liver failure and transplantation in western. More than 75 percent of idiosyncratic drug reactions result in liver transplantat. Druginduced liver injury dili therefore poses a major clinical problem. Many of the commonly used antitb drugs are associated with significant potential of causing hepatotoxicity. Despite the beneficial effects of inh, severe adverse effects especially peripheral neuropathy and hepatotoxicity are associated with inh therapies4, 5, 6, 7.
Hepatotoxicity was induced by oral administration of inh 50mgkg and rif 100mgkg on every 72hrs for a period of 21days. Sterling, on behalf of the ats hepatotoxicity of antituberculosis therapy subcommittee this of. Kleiner, md, phd, laboratory of pathology, national cancer institute. Metabolism of inh leads to the production of hydrazine via both direct and indirect pathways. There is currently no way to reimburse for the absence of liver function. Druginduced hepatotoxicity of antituberculosis drugs and. Druginduced hepatic injury accounts for more than 50 percent of cases of acute liver failure in the united states.
Inh metabolism has been thought to be associated with inh induced liver injury. Previous studies have established and used a dosage of 50 mgkg b. Hepatoprotective activity of canthium dicoccum in isoniazid. However, it can cause liver injury and even liver failure. Aug 03, 2016 isoniazid inh is highly effective for the management of tuberculosis. Isoniazid isonicotinylhydrazine, inh is the most active drug for the treatment of tuberculosis caused by susceptible strains. Antihypertensive agents have been associated with adverse reactions that, if unrecognized by health practitioners, may have devastating consequences. Hepatotoxicity induced by antituberculosis drugs among. Hepatotoxicity associated with isoniazid preventive therapy.
Idiosyncratic unpredictable druginduced liver injury is one of the most challenging liver disorders. Ecd was administered orally for 21 days 150 and 300mgkg body weight. Capitals indicate lifethreatening, underlines indicate most frequent. Drug induced hepatic injury accounts for more than 50 percent of cases of acute liver failure in the united states. A model of isoniazidinduced hepatotoxicity in rabbits. Severe hepatotoxicity serum transaminase 10 times the upper limit of normal occurred in 6. The predominant clinical presentation is acute hepatitis andor cholestasis, although almost any clinical pathological pattern of acute or chronic liver disease can occur. The incidence of isoniazid inh and rifampicin rif induced abnormal liver enzyme activity is 27% but only 19% with inh alone. Zidovudine and isoniazid induced liver toxicity and oxidative stress. Mar 24, 2017 we describe drug induced liver injury dili secondary to antituberculous treatment att in a large tuberculosis tb centre in london. Pdf protective effects of quercetin against isoniazid and. Severe hepatotoxicity serum transaminase 10 times the upper limit of. Fatal hepatotoxicity induced by hydralazine or labetalol janice l. The manifestations of druginduced hepatotoxicity are highly variable, ranging from asymptomatic elevation of liver enzymes to fulminant hepatic failure.
Selected pharmaceutical excipient prevent isoniazid and. The base of evidence for isoniazid hepatotoxicity, including a level of risk in the range of 5 to 20 cases of hepatotoxicity expected per persons receiving treatment with a 1% to 10% casefatality rate, is composed of studies done more than 20 years ago. An infrequent but preventable cause of liver failure in children treated for latent tuberculosis infection dan desrochers, 1 regino p. Case report acute and fatal isoniazidinduced hepatotoxicity. There is evidence that the inh metabolite hydrazine plays an important role in the mechanism of this toxicity. Life expectancy is prolonged, and quality of life is much improved.
Treatment finally consisted of rifampicin 600mg, ethambutol 1 g, pyrazinamide 15g, and ofloxacin 400mgday. It is a small molecule mw7 that is freely soluble in water. Background isoniazid inh, a key drug of antituberculosis therapy, is metabolized by arylamine nacetyltransferase2 nat2, cytochrome p450 2e1 cyp2e1 and glutathione stransferase gst. Although druginduced liver injury dili caused by different drugs is somewhat different, the clinical characteristics of inhinduced liver injury. Saroufim 2 department of pharmacy practice, school of pharmacy, lebanese american university lau, p. The various types are shown in figure 1 and discussed below in brief. Jul 15, 2016 there are few data on hepatotoxicity induced by acute or chronic paracetamol poisoning in the pediatric population. Isoniazid inh is highly effective for the management of tuberculosis. Current concepts of mechanisms in druginduced hepatotoxicity. Druginduced liver injury covers a variety of types, and includes most of the clinical and pathological expressions of liver damage 6. The purpose of this study was to investigate whether antitb dih is associated with basal serum drug levels. The manifestations of drug induced hepatotoxicity are highly variable, ranging from asymptomatic elevation of liver enzymes to fulminant hepatic failure. Druginduced liver injury from antituberculous treatment.
Drug induced hepatotoxicity is a frequent cause of liver injury. The standard therapies for tb include a combination treatment of isoniazid inh, rifampicin, pyrazinamide, and ethambutol2. Mar 23, 2011 isoniazidinduced severe hepatotoxicity. Hepatotoxicity induced by acute and chronic paracetamol. Fatal hepatotoxicity induced by hydralazine or labetalol. Cyp2e1 genotype and isoniazid induced hepatotoxicity in patients treated for latent tuberculosis article pdf available in european journal of clinical pharmacology 626. The incidence rate of antitb induced hepatotoxicity is found to be 2% to 28%. There are few data on hepatotoxicity induced by acute or chronic paracetamol poisoning in the pediatric population. The advances in science and medicine we are now experiencing are unprec edented and exciting. American journal of respiratory and critical care medicine. Isoniazid inh, a widely used drug in the prophylaxis and treatment of tuberculosis, is associated with a 1 to 2% risk of severe and potentially fatal hepatotoxicity. Diagnosis, management and prevention of druginduced liver injury. Transporters, enzymes, and excretion druginduced liver injury.
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