From the Guidelines
Drug-induced fulminant hepatitis is a severe, rapidly progressing liver inflammation caused by medication toxicity that leads to acute liver failure within weeks of onset in patients without pre-existing liver disease. This condition can be triggered by various medications, including acetaminophen, antibiotics like isoniazid and amoxicillin-clavulanate, antiepileptics such as valproic acid, and certain herbal supplements 1. The pathophysiology typically involves either direct hepatotoxicity where medications damage liver cells directly, or idiosyncratic reactions where the immune system attacks the liver in response to drug exposure 1. Some of the key medications that can cause this condition include:
- Carbamazepine
- Methyldopa
- Minocycline
- Macrolide antibiotics
- Nitrofurantoin
- Statins
- Sulfonamides
- Terbinafine
- Chlorpromazine
- Methotrexate Treatment requires immediate discontinuation of the offending drug and supportive care, with severe cases potentially requiring liver transplantation 1. Early recognition is crucial as mortality rates can exceed 80% without appropriate intervention. Patients with risk factors such as advanced age, female gender, malnutrition, or pre-existing liver conditions should be monitored more closely when taking potentially hepatotoxic medications. It is essential to exercise clinical judgment to determine the relative contribution of a drug or drugs alongside possible concomitant liver disease, considering the pattern of liver blood tests, the timing of medication use, and the clinical setting 1. In cases where the diagnosis is uncertain, a trial of steroid treatment and close observation upon steroid tapering and possible withdrawal is recommended 1.
From the FDA Drug Label
Severe and sometimes fatal hepatitis associated with isoniazid therapy has been reported and may occur or may develop even after many months of treatment. Isoniazid-associated hepatitis usually occurs during the first three months of treatment If abnormalities of liver function exceed three to five times the upper limit of normal, discontinuation of isoniazid should be strongly considered Patients should be instructed to immediately report signs or symptoms consistent with liver damage or other adverse effects If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.
Drug-induced fulminant hepatitis is a severe and potentially fatal liver condition associated with isoniazid therapy, which may occur even after months of treatment. Key characteristics include:
- Severe liver dysfunction
- Onset often within the first three months of treatment
- Abnormalities of liver function exceeding three to five times the upper limit of normal
- Symptoms such as unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, and abdominal tenderness If these symptoms appear, isoniazid should be discontinued promptly to prevent further liver damage 2.
From the Research
Definition and Causes of Drug-Induced Fulminant Hepatitis
- Drug-induced fulminant hepatitis is a severe and life-threatening condition characterized by the development of acute liver failure, often with encephalopathy, in individuals with previously normal liver function or well-compensated liver disease 3.
- The etiology of fulminant hepatic failure can be attributed to a wide variety of causes, including toxin-induced or viral hepatitis, with drugs being a common cause of liver injury 4, 3.
- Specific drugs that can cause liver injury include acetaminophen, antibiotics, antiepileptics, and antituberculous drugs, which are among the most common causes of drug-induced liver injury 4.
Diagnosis and Clinical Features
- The diagnosis of drug-induced liver injury (DILI) relies on the exclusion of other etiologies of liver disease, as specific biomarkers are still lacking 5, 6.
- Clinical scales such as CIOMS/RUCAM can support the diagnostic process, but need refinement 5.
- DILI can present with a variety of phenotypes, mimicking other hepatic diseases, and can range from mild liver enzyme elevations to liver failure, transplantation, or death 5, 6.
Severity Assessment and Treatment
- Severity assessment of acute hepatitis is critical, and acute liver failure (ALF) is defined by the factor V, with fulminant hepatitis characterized by the presence of encephalopathy in the first two weeks after the onset of jaundice 4.
- Treatment with N-acetylcysteine can effectively reduce progression to ALF if given early after an acute overdose of acetaminophen, but liver transplantation is the only routinely used life-saving therapy once ALF has developed 4, 7.
- Orthotopic liver transplantation is the only therapy proven to improve patient survival in the majority of patients with fulminant hepatic failure 3.