A 45-year-old woman comes to the office due to cough with hemoptysis, night sweats, and subjective fever. A chest radiograph demonstrates right upper lobe cavity that is consistent with a diagnosis of pulmonary tuberculosis. Sputum staining for acid-fast bacteria is positive. She is begun on a regimen that includes isoniazid, rifampin, ethambutol, and pyrazinamide. The patient has a history of alcohol use disorder. She has taken oral contraceptive pills for the past 5 years. Two months later when she returns for follow-up examination, her sputum is clear of acid-fast bacilli. However, she now has fatigue, malaise, and nausea that began approximately 10 days ago. Physical examination reveals icteric sclerae and tender hepatomegaly. Laboratory results are as follows: Liver studies
Coagulation studies
Hepatitis panel
Liver biopsy demonstrates panlobular mononuclear infiltration and hepatic cell necrosis. Which of the following is the most likely diagnosis?

Question

A 45-year-old woman comes to the office due to cough with hemoptysis, night sweats, and subjective fever.  A chest radiograph demonstrates right upper lobe cavity that is consistent with a diagnosis of pulmonary tuberculosis. Sputum staining for acid-fast bacteria is positive.  She is begun on a regimen that includes isoniazid, rifampin, ethambutol, and pyrazinamide.  The patient has a history of alcohol use disorder.  She has taken oral contraceptive pills for the past 5 years.  Two months later when she returns for follow-up examination, her sputum is clear of acid-fast bacilli.  However, she now has fatigue, malaise, and nausea that began approximately 10 days ago.  Physical examination reveals icteric sclerae and tender hepatomegaly.  Laboratory results are as follows: Liver studies
 Coagulation studies
 Hepatitis panel
 Liver biopsy demonstrates panlobular mononuclear infiltration and hepatic cell necrosis.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This patient's liver function tests and liver biopsy result are consistent with a diagnosis of acute hepatitis. However, the negative viral serology results indicate an infectious cause of her hepatitis is unlikely. Since this patient is on isoniazid, idiosyncratic liver injury with a histological picture similar to viral hepatitis must be considered. Although extrahepatic hypersensitivity manifestations like rash, arthralgias, fever, leukocytosis, and eosinophilia are common in patients with drug-induced liver injury, they are characteristically absent in cases of isoniazid-induced hepatic cell injury. Drugs and toxins typically cause hepatic injury, either through direct toxic effects or through idiosyncratic reactions. The direct toxic effects are dose-dependent and have short latent periods. Examples of direct toxins include acetaminophen and substances found in the Amanita phalloides mushroom. Idiosyncratic reactions are not dose-dependent and have variable latent periods. Some examples of pharmacological agents that cause idiosyncratic reactions include isoniazid, chlorpromazine, and antiretroviral therapy. Amanita phalloides Drug-induced liver disease can also be broadly categorized according to morphology: cholestasis (eg, anabolic steroids), fatty liver (eg, valproate), hepatitis (as in this patient), toxic or fulminant liver (eg, acetaminophen), or granulomatous (eg, allopurinol). (Choice A) The patient's laboratory profile is not suggestive of alcoholic hepatitis. Classically, the AST:ALT ratio is >2 in alcoholic hepatitis. Moreover, the timeline correlation between the initiation of treatment for tuberculosis and the onset of her hepatic dysfunction mandates close scrutiny of her pharmacotherapy regimen. (Choice B) Oral contraceptives are unusual in that they can cause abnormalities in liver function tests without evidence of necrosis or fatty change. As this patient's liver biopsy demonstrated necrosis, oral contraceptives are not likely responsible for her hepatic dysfunction. (Choice D) Autoimmune hepatitis should be considered once all possible causes of drug-induced or viral hepatitis have been ruled out. Positive antinuclear antibody (ANA) and/or positive smooth muscle antibody suggest the diagnosis of classic (type 1) autoimmune hepatitis. (Choice E) Tuberculous hepatitis may develop in cases of miliary tuberculosis but would be characterized by granulomas on liver biopsy. Moreover, since this patient had a sputum conversion, it is highly unlikely that she is now suffering from miliary tuberculosis. Educational objective: Isoniazid causes idiosyncratic liver injury with histological features similar to those seen in patients with viral hepatitis.

A 45-Year-Old Woman Comes to the Office Due to Cough