Fulminant Hepatic Failure in Association With Quetiapine
Fulminant Hepatic Failure in Association With Quetiapine
A 59-year-old Caucasian woman with a prior history of Parkinson's disease was on carbidopa-levodopa combination for three years and oxazepam along with pramipexole for six months before she developed hallucinations that were attributed to pramipexole therapy. Subsequently, pramipexole was discontinued and our patient was given quetiapine to treat her hallucinations. She had received six weeks of quetiapine therapy before presenting to our hospital with the main complaint of feeling unwell for three weeks. Her symptoms were accompanied with nausea, vomiting, decrease appetite and abdominal pain for a few days duration. She had also noticed a yellowish discoloration of her sclera but no change in the color of urine or stool. There was no accompanying history of fever, chills or rigors. No risk factors or history suggestive of familial liver disease was provided. She was a non-smoker and denied drinking alcohol.
The results of a general physical examination revealed a stable hemodynamic status with bilateral icterus but no pallor, cyanosis or lymphadenopathy. An abdominal examination demonstrated distention with tenderness in the right upper quadrant but no clinically detectable ascites or hepatosplenomegaly. No other stigmata of chronic liver disease were seen. Cardiovascular and respiratory system examinations were unremarkable. No abnormality was detected on the neurological examination.
Admission blood test results showed a normal hemogram and normal renal function tests including electrolytes but deranged liver function tests (alanine aminotransferase: 71IU/L; aspartate aminotransferase: 740IU/L; lactate dehydrogenase: 737IU/L; γ-glutamyl transferase: 509IU/L; alkaline phosphatase: 196IU/L; total bilirubin: 244μmol/L and an international normalized ratio (INR) of 2.7). Her blood ethanol level was in the normal range. Viral serology test results for hepatitis A, B and C were negative. A vasculitic screen was performed, which revealed an anti-nuclear antibody titer of 1:1600 and positive anti-double-stranded deoxyribonucleic acid (dsDNA) results, but negative results for anti-liver kidney microsomal antibody. Tests for anti-neutrophil cytoplasmic antibodies showed negative results for anti-myeloperoxidase but were equivocal for anti-proteinase 3. Normal α-1 anti-trypsin levels (1.89μmol/L) and normal levels for other immunoglobulins were found (IgG: 34g/L, IgA: 2.44g/L and IgM: 1.5g/L). The results of screening tests for Wilson's disease and hemochromatosis were also negative.
An ultrasound scan of the abdomen showed a distended gall bladder with absence of stones and no free fluid in the abdomen. The liver and spleen sizes were reported as within normal ranges. Computerized tomography of the abdomen confirmed the absence of intra-hepatic biliary dilatation.
In view of the above-mentioned findings and her history, our patient was admitted with a probable diagnosis of quetiapine-induced hepatitis. Quetiapine was discontinued but other medications, that is, carbidopa-levodopa and oxazepam, were not stopped. The initial treatment was mainly supportive. However, within 48 hours of admission, our patient demonstrated signs of encephalopathy in the form of confusion, astrexis and impaired level of consciousness with the development of significant ascitis. She was subsequently transferred to the intensive care unit and the local liver transplant team was consulted for probable transplant. After ruling out spontaneous bacterial peritonitis, our patient was treated with lactulose, spironolactone and furosemide. She was also given methyprednisolone 20mg intravenously. A follow-up abdominal ultrasound scan revealed splenomegaly, coarse liver parenchyma and ascitis but no focal lesions or cholelithiasis. The hepatic and portal circulations were patent on Doppler examination. A trans-jugular liver biopsy confirmed extensive confluent and bridging necrosis predominantly in zone 3. The portal area contained mild to focally moderate mixed inflammatory cellular infiltrate consisting of lymphocytes, macrophages, eosinophils and a few polymorphonuclear cells along the boundaries of the necrotic areas. The parenchyma showed variable degrees of hepatocellular degeneration and mild mixed inflammatory cellular infiltrate consisting mainly of lymphocyes and macrophages with few plasma cells and prominent Kupffer cells. The overall histopathological picture was reported to be suggestive of an acute hepatitis with confluent and bridging necrosis, indicative of drug-induced liver injury.
Our patient's clinical symptoms improved gradually accompanied by improvement in biochemical parameters over the course of her stay in the intensive care unit. The encephalopathy resolved completely with improvement in icterus, nutritional status and oral intake. Later on, she was transferred out of the intensive care unit to the general ward and put on a tapering dose of oral prednisolone starting at 40mg/day.
She was discharged home in a stable condition approximately six weeks after the initial admission on 20mg prednisolone per day with a suggested tapering of 5mg every week. She was advised against taking quetiapine in the future. Follow-up blood test results eight weeks after discharge revealed mildly elevated liver enzymes (less than twice the upper limit of normal) with normal synthetic and excretory hepatic functions.
Case Presentation
A 59-year-old Caucasian woman with a prior history of Parkinson's disease was on carbidopa-levodopa combination for three years and oxazepam along with pramipexole for six months before she developed hallucinations that were attributed to pramipexole therapy. Subsequently, pramipexole was discontinued and our patient was given quetiapine to treat her hallucinations. She had received six weeks of quetiapine therapy before presenting to our hospital with the main complaint of feeling unwell for three weeks. Her symptoms were accompanied with nausea, vomiting, decrease appetite and abdominal pain for a few days duration. She had also noticed a yellowish discoloration of her sclera but no change in the color of urine or stool. There was no accompanying history of fever, chills or rigors. No risk factors or history suggestive of familial liver disease was provided. She was a non-smoker and denied drinking alcohol.
The results of a general physical examination revealed a stable hemodynamic status with bilateral icterus but no pallor, cyanosis or lymphadenopathy. An abdominal examination demonstrated distention with tenderness in the right upper quadrant but no clinically detectable ascites or hepatosplenomegaly. No other stigmata of chronic liver disease were seen. Cardiovascular and respiratory system examinations were unremarkable. No abnormality was detected on the neurological examination.
Admission blood test results showed a normal hemogram and normal renal function tests including electrolytes but deranged liver function tests (alanine aminotransferase: 71IU/L; aspartate aminotransferase: 740IU/L; lactate dehydrogenase: 737IU/L; γ-glutamyl transferase: 509IU/L; alkaline phosphatase: 196IU/L; total bilirubin: 244μmol/L and an international normalized ratio (INR) of 2.7). Her blood ethanol level was in the normal range. Viral serology test results for hepatitis A, B and C were negative. A vasculitic screen was performed, which revealed an anti-nuclear antibody titer of 1:1600 and positive anti-double-stranded deoxyribonucleic acid (dsDNA) results, but negative results for anti-liver kidney microsomal antibody. Tests for anti-neutrophil cytoplasmic antibodies showed negative results for anti-myeloperoxidase but were equivocal for anti-proteinase 3. Normal α-1 anti-trypsin levels (1.89μmol/L) and normal levels for other immunoglobulins were found (IgG: 34g/L, IgA: 2.44g/L and IgM: 1.5g/L). The results of screening tests for Wilson's disease and hemochromatosis were also negative.
An ultrasound scan of the abdomen showed a distended gall bladder with absence of stones and no free fluid in the abdomen. The liver and spleen sizes were reported as within normal ranges. Computerized tomography of the abdomen confirmed the absence of intra-hepatic biliary dilatation.
In view of the above-mentioned findings and her history, our patient was admitted with a probable diagnosis of quetiapine-induced hepatitis. Quetiapine was discontinued but other medications, that is, carbidopa-levodopa and oxazepam, were not stopped. The initial treatment was mainly supportive. However, within 48 hours of admission, our patient demonstrated signs of encephalopathy in the form of confusion, astrexis and impaired level of consciousness with the development of significant ascitis. She was subsequently transferred to the intensive care unit and the local liver transplant team was consulted for probable transplant. After ruling out spontaneous bacterial peritonitis, our patient was treated with lactulose, spironolactone and furosemide. She was also given methyprednisolone 20mg intravenously. A follow-up abdominal ultrasound scan revealed splenomegaly, coarse liver parenchyma and ascitis but no focal lesions or cholelithiasis. The hepatic and portal circulations were patent on Doppler examination. A trans-jugular liver biopsy confirmed extensive confluent and bridging necrosis predominantly in zone 3. The portal area contained mild to focally moderate mixed inflammatory cellular infiltrate consisting of lymphocytes, macrophages, eosinophils and a few polymorphonuclear cells along the boundaries of the necrotic areas. The parenchyma showed variable degrees of hepatocellular degeneration and mild mixed inflammatory cellular infiltrate consisting mainly of lymphocyes and macrophages with few plasma cells and prominent Kupffer cells. The overall histopathological picture was reported to be suggestive of an acute hepatitis with confluent and bridging necrosis, indicative of drug-induced liver injury.
Our patient's clinical symptoms improved gradually accompanied by improvement in biochemical parameters over the course of her stay in the intensive care unit. The encephalopathy resolved completely with improvement in icterus, nutritional status and oral intake. Later on, she was transferred out of the intensive care unit to the general ward and put on a tapering dose of oral prednisolone starting at 40mg/day.
She was discharged home in a stable condition approximately six weeks after the initial admission on 20mg prednisolone per day with a suggested tapering of 5mg every week. She was advised against taking quetiapine in the future. Follow-up blood test results eight weeks after discharge revealed mildly elevated liver enzymes (less than twice the upper limit of normal) with normal synthetic and excretory hepatic functions.