Acute and Fatal Isoniazid-Induced Hepatotoxicity: A Case Report and Review of the Literature

Abstract

This paper describes a case of an acute and fatal isoniazid-induced hepatotoxicity and provides a review of the literature. A 65-year-old female diagnosed with latent Mycobacterium tuberculosis infection was receiving oral isoniazid 300 mg daily. She was admitted to the hospital for epigastric and right sided flank pain of one-week duration. Laboratory results and imaging confirmed hepatitis. After ruling out all other possible causes, she was diagnosed with isoniazid-induced acute hepatitis (probable association by the Naranjo scale). After discharge, the patient was readmitted and suffered from severe coagulopathy, metabolic acidosis, acute kidney injury, hepatic encephalopathy, and cardiorespiratory arrest necessitating two rounds of cardiopulmonary resuscitation. Despite maximal hemodynamic support, the patient did not survive. A review of the literature, from several European countries and the United States of America, revealed a low incidence of mortality due to isoniazid-induced hepatotoxicity when used as a single agent for latent Mycobacterium tuberculosis infection. As for the management, the first step consists of withdrawing isoniazid and rechallenge is usually discouraged. Few treatment modalities have been proposed; however there is no robust evidence to support any of them. Routine monitoring for hepatotoxicity in patients receiving isoniazid is warranted to prevent morbidity and mortality.

Serious hepatotoxicity following use of isoniazid preventive therapy in HIV patients in Eritrea

“…Isoniazid (INH) has been in use since many years as prophylaxis of TB and has been associated with small risk of fatal hepatotoxicity that ranges from 0.003% to 0.06% . Liver injuries with fatal outcomes have been reported to the US‐CDC and other published case reports also reported fatal hepatotoxicity associated with INH preventive therapy. Age >35 years, alcohol consumption and concurrent administration of other hepatotoxic agents are identified as possible risk factors for the INH‐induced hepatotoxicity.…”

Isoniazid Induced Liver Injury; a Case Series and Review

“…[4] Although hepatotoxicity is a well-known side effect of INH, mortality rates remain low as reported in the literature. [5] Other risk factors are well-confirmed including age, alcohol consumption, the concomitant administration of other hepatotoxic drugs such as acetaminophen, methotrexate, sulfasalazine, or carbamazepine, Underlying liver disease. Hepatitis B virus infection, Hepatitis C virus infection, HIV infection, Acetylator phenotype, N-acetyltransferase (NAT) activity Glutathione S-transferase activity.…”

“…Hepatitis B virus infection, Hepatitis C virus infection, HIV infection, Acetylator phenotype, N-acetyltransferase (NAT) activity Glutathione S-transferase activity. [5][6] It is important for clinicians and pharmacists to appropriately follow up patients, counsel them on the signs and symptoms of hepatotoxicity, and encourage them to report it. [5] The Purpose of our study is to demonstrate the importance of INH as Potential Hepatotoxic agent.…”

“…[5][6] It is important for clinicians and pharmacists to appropriately follow up patients, counsel them on the signs and symptoms of hepatotoxicity, and encourage them to report it. [5] The Purpose of our study is to demonstrate the importance of INH as Potential Hepatotoxic agent. The aim of this series of Isoniazid-induced liver injury is to demonstrate the importance of isoniazid as a potential hepatotoxic agent.…”

New short regimens for latent tuberculosis treatment: safety first!

“…The more widespread use of IPT was followed, within a year, by reports of fatal hepatotoxicity [5]. This has continued to be the Achilles' heel of IPT: although fatality rates are now low, "liver deaths" continue to occur with IPT [6]. 60 years later, awareness about this drawback is widespread among providers and patients, resulting in low rates of prescription [3] and acceptance [7].…”