Hydralazine-Induced Cholestatic Hepatitis

Abstract

Hydralazine has been widely used for treating hypertension, particularly in patients with renal failure. We report a case on a patient in whom we believe the drug was implicated in an otherwise unexplained disturbance of liver function. A 63-year-old African-American female with medical history of hypertension and end-stage renal disease (on hemodialysis) was admitted to the hospital with epigastric pain and jaundice. The symptoms started about 1 week ago. Initial laboratory tests showed abnormal liver enzymes with elevated conjugated bilirubin and alkaline phosphatase suggestive of cholestatic jaundice. Amylase and lipase were normal. Abdominal ultrasound showed normal caliber common bile duct without evidence of obstruction. Abdominal CT scan does not show any evidence of intra- or extrahepatic biliary ductal dilatation, and no mass lesions were seen in the pancreas. Further blood chemistry showed worsening of liver enzymes and increased bilirubin over the next 2-3 days. Magnetic resonance cholangiopancreatography failed to show any evidence of intra- or extrahepatic biliary ductal dilatation. No other laboratory evidence of cholestatic jaundice was found. Before proceeding for invasive diagnostic procedure, that is, endoscopic retrograde cholangiopancreatography, the patient's drug history was reviewed. She was on hydralazine 75 mg 3 times per day, started 5 months ago. At that time, her liver function tests were normal. As we could not find any other cause of cholestatic jaundice, we attributed this as a side effect of hydralazine. A trial was given by stopping the hydralazine. It was seen that there was significant improvement in the liver function enzymes over the next week. Complete clinical and biochemical recovery occurred over the next 4 weeks. Liver injury after long-term therapy with hydralazine and after short-term therapy with hydralazine (2-10 days) has been described. Hydralazine-induced hepatotoxicity may manifest as hypersensitivity-type injury, mixed hepatocellular injury, acute hepatitis, cholestatic jaundice, or centrilobular necrosis. The Hydralazine-induced cholestatic liver injury seems to be fully reversible. Complete clinical and biochemical recovery occurs after discontinuation of the drug. Also, the differential diagnosis of any patient with hepatocellular injury should include medications. This will prevent unnecessary diagnostic tests.

A Suspected Case of Hydralazine-Induced Hepatotoxicity: A Case Report and Review of Literature

“…Two different types of injury pattern to the liver have been reported with hydralazine. There have been reports of hydralazine-induced hepatotoxicity with a short latency period ranging from 2 to 6 weeks [ 7 ], and there have also been case reports with latency periods ranging from 2 months to 1 year [ 8 ]. In our case, the patient was started on hydralazine 3 weeks before the onset of clinical symptoms and the onset of transaminitis.…”

“…Autoantibodies were also found to be associated with cases with long latency. The recovery is typically prolonged and these cases tend to be associated with lupus-like syndrome [ 8 ]. Autoantibodies to cytochrome P450 system (CYP1A2) were found in patients with hepatotoxicity due to dihydralazine (not available in the US), which is structurally similar to hydralazine [ 9 ].…”

α-Methyldopa-induced hepatitis during the postpartum period

“…We did not feel that hydralazine contributed to the disorder in this instance, as it was discontinued in the early postpartum period. Although hydralazine has been documented to cause hepatitis manifesting as a hypersensitivity-type injury, with mixed hepatocellular injury, acute hepatitis, cholestatic jaundice or centrilobular necrosis with case reports noted in the literature 13 14…”