American Journal of Therapeutics 0, 1–2 (2014)

A One-Two Punch: Hydralazine-Induced Liver Injury in a Recovering Ischemic Hepatitis Ahmed Alansari, MD, Luis Quiel, MD, and Noella Boma, MD*

A 77-year-old woman presented to the emergency department with a 2-day history of nausea and vomiting. Her medical history included diabetes mellitus, hypertension, atrial fibrillation, dilated cardiomyopathy, and coronary artery disease. Her home medications included aspirin, clopidogrel, warfarin, digoxin, metoprolol, losartan, simvastatin, isosorbide dinitrate, furosemide, and spironolactone. Initial physical examination showed blood pressure of 170/80 mm Hg with a heart rate of 69 beats per minute, otherwise unremarkable. Initial laboratory workup was significant for INR of 3.6, with slightly elevated troponin I and creatinine of 0.06 ng/mL and 1.4 mg/dL, respectively. The patient was admitted to the medicine floor. However, a few hours later, her atrial fibrillation went into rapid ventricular response, associated with hypotension. Cardiac enzymes began to trend up along with worsening of her renal function tests and hepatic enzymes. Her INR remained supratherapeutic despite holding coumadin and giving vitamin K. The patient was transferred to the medical intensive care unit for closer monitoring. During day 1 of the medical intensive care unit stay, losartan, simvastatin, and diuretics were held, whereas aspirin, clopidogrel, and isosorbide dinitrate were continued. In the following 2 days, there was worsening of tissue perfusion, and laboratory workup showed AST 514 IU/L, ALT 391 IU/L, INR .9, creatinine 3.8 mg/dL, and troponin I 0.19 ng/mL; therefore, digoxin was also held. Once the patient achieved hemodynamic stability, she was started on hydralazine. On day 4, renal function, cardiac, and hepatic enzymes improved significantly. However, 24 hours later, transaminases began to trend up again reaching a maximum of AST and ALT of 359 and 525 IU/L, respectively. Other possible causes were ruled out because her viral hepatitis markers, antihistone antibody, antinuclear antibody, and anti–double-stranded DNA were all negative. After thorough review of all medications, hydralazine was held with subsequent improvement in transaminases. The patient was seen a month later after her discharge, and all her laboratory workup improved to baseline. Keywords: hydralazine, liver injury, ischemic hepatitis

INTRODUCTION Systemic hypotension alone does not cause ischemic hepatitis; almost all patients who develop ischemic hepatitis have a pre-existing congestion of their liver secondary to underlying severe cardiac disease.1 Department of Internal Medicine, Metropolitan Hospital Center, New York Medical College, New York, NY. The authors have no conflicts of interest to declare. *Address for correspondence: Department of Medicine, Metropolitan Hospital Center, 1901 First Avenue, Medicine Department, New York, NY 10029. E-mail: [email protected] 1075–2765  2014 Lippincott Williams & Wilkins

Liver injury can be caused by many prescribed drugs and over-the-counter medications through different mechanisms, in this case hydralazine.2,3 We are presenting a case of hydralazine-induced liver injury in a patient with recovering ischemic hepatitis secondary to severe underlying heart disease, as a part of multiorgan failure after an episode of hemodynamic instability.

CASE PRESENTATION A 77-year-old woman presented to the emergency department with a 2-day history of nausea and vomiting, with no other associated gastrointestinal www.americantherapeutics.com

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symptoms. Her medical history included diabetes mellitus type 2, hypertension, atrial fibrillation, dilated cardiomyopathy, coronary artery disease, and history of non-ST elevation myocardial infarction. Her home medications included aspirin, clopidogrel, warfarin, digoxin, metoprolol ER, losartan, simvastatin, isosorbide dinitrate, furosemide, and spironolactone. Initial physical examination showed blood pressure of 170/ 80 mm Hg with a heart rate of 69 beats per minute, otherwise unremarkable. Initial laboratory workup was significant for supratherapeutic INR of 3.6, with slightly elevated troponin I and creatinine of 0.06 ng/ mL and 1.4 mg/dL, respectively. The rest of the laboratory workup was within normal limits. The patient was admitted to the medicine floor. However, a few hours after admission, her atrial fibrillation went into rapid ventricular response, associated with hypotension. Cardiac enzymes began to trend up along with worsening of her renal and hepatic enzymes. Her INR remained supratherapeutic despite holding coumadin and giving vitamin K. The patient was transferred to the medical intensive care unit for heart rate control and close monitoring. She was started on metoprolol and received a bolus of normal saline. During day 1 of the medical intensive care unit stay, losartan, simvastatin, and diuretics were held, whereas aspirin, clopidogrel, and isosorbide dinitrate were continued. In the following 2 days, there was worsening of tissue perfusion. Laboratory workup indicated AST 514 IU/L, ALT 391 IU/L, INR .9, creatinine 3.8 mg/dL, and troponin I 0.19 ng/mL; therefore, digoxin was also held. Once the patient achieved hemodynamic stability, she was started on hydralazine. On day 4, renal function, cardiac, and hepatic enzymes improved significantly. However, 24 hours after starting hydralazine, transaminases began to trend up again reaching a maximum of AST and ALT of 359 and 525 IU/L, respectively. Other possible causes were

American Journal of Therapeutics (2014) 0(0)

Alansari et al

ruled out as her viral hepatitis markers, antihistone antibody, antinuclear antibody, and anti–doublestranded DNA were all negative. After thorough review of all medications, hydralazine was held with subsequent improvement in transaminases. The patient was seen a month later after her discharge, and all her laboratory workup improved to baseline.

DISCUSSION In this case, the initial elevation of the hepatic enzymes was secondary to ischemic hepatitis given the patient’s underlying severe heart disease complicated with super imposed hypotension and hemodynamic instability. We suggest that the second elevation of the hepatic enzymes, after the transient drop, is secondary to hydralazine induced liver injury. This theory is supported by the dramatic improvement in laboratory values after holding hydralazine and a significant increase in the blood eosinophil level. Other etiologies of liver injury were ruled out with negative viral hepatitis markers, antihistone antibody, antinuclear antibody, and anti–double-stranded DNA, further supporting hydralazine as the cause. The limitations in this case include a lack of lactate dehydrogenase enzyme levels, and the absence of liver biopsy that was not done given the patients general condition, compounded by her oral anticoagulation therapy.

REFERENCES 1. Seeto RK, Fenn B, Rockey DC. Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med. 2000;109:109. 2. Lee WM. Drug-induced hepatotoxicity. N Engl J Med. 2003;349:474. 3. Chang CY, Schiano TD. Review article: drug hepatotoxicity. Aliment Pharmacol Ther. 2007;25:1135.

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A One-Two Punch: Hydralazine-Induced Liver Injury in a Recovering Ischemic Hepatitis.

A 77-year-old woman presented to the emergency department with a 2-day history of nausea and vomiting. Her medical history included diabetes mellitus,...
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