Acute vanishing bile duct syndrome after ibuprofen therapy in a child

doi:10.1016/j.jpeds.2004.05.027

The Journal of Pediatrics

Volume 145, Issue 2, August 2004, Pages 273-276

https://doi.org/10.1016/j.jpeds.2004.05.027 Get rights and content

Abstract

We report the case of a 10 year-old girl who had Stevens-Johnson syndrome and cholestasis after ibuprofen therapy. Liver histology was compatible with vanishing bile duct syndrome. She received ursodeoxycholic acid, and liver tests normalized within 7 months. This report confirms that ibuprofen may induce acute vanishing bile duct syndrome.

Section snippets

Case Report

A 10-year-old girl had fever during 2 days and rhinopharyngitis; she received ibuprofen at conventional pediatric doses (maximum of 30 mg/kg/day). Eight days later, the fever relapsed, and she received again ibuprofen. Two days later, maculopapular pruriginous rash appeared on the face. Forty-eight hours later, she was hospitalized because of jaundice, dark urine, discolored stools, arthralgia, cheilitis, conjunctivitis, pharyngeal erythema, and extension of maculopapular rash to the whole body

Discussion

Acute vanishing bile duct syndrome is a rare cause of prolonged and progressive cholestasis and is often clinically associated to fever, fatigue, upper abdominal pain, and skin rash.2., 6. Serum liver tests comprise a generally mild increase in transaminase activities with high total bilirubin concentration, persistently elevated alkaline phosphatase and gamma-glutamyl transpeptidase activities, and hypercholesterolemia. The acute symptoms usually subside within days or weeks. Prolonged

Acknowledgements

We are grateful to Drs O. Bernard, N. Khayat, J. M. Estavoyer, B. Hoen, P. Colin, J. P. Carbillet, B. Coupe, P. Thierry, J. M. Jacquet, and N. Haghiri for taking care of the patients and for helpful comments.

References (19)

A.P. Geubel et al.
Bile duct disorders
Clin Liver Dis
(2003)
M. Srivastava et al.
Drug associated acute-onset vanishing bile duct and Stevens-Johnson Syndrome in a child
Gastroenterology
(1998)
S. Fiorucci et al.
Cyclo-oxygenase isoenzymes: structural basis for selective inhibition of cyclo-oxygenases by anti-inflammatory agents
Dig Liver Dis
(2001)
G. Paumgartner et al.
Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited
Hepatology
(2002)
C. Degott et al.
Drug-induced prolonged cholestasis in adults: a histological semi-quantitative study demonstrating progressive ductopenia
Hepatology
(1992)
M. Hadchouel
Paucity of interlobular bile ducts
Semin Diagn Pathol
(1992)
J. Ludwig
Vanishing bile duct syndrome
K.N. Furuya et al.
Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis
J Pediatr Gastroenterol Nutr
(1991)
I. Alam et al.
Vanishing bile duct syndrome temporally associated with ibuprofen use
Am J Gastroenterol
(1996)

There are more references available in the full text version of this article.

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Management of DILI involves removal of the offending drug and addressing additional symptoms. Case reports have reported VBDS with DILI [8]; however, knowledge in this area is very scarce. Thus far, no significant analytical studies have investigated the characteristics of this condition or its treatment and outcomes.
Vanishing bile duct syndrome (VBDS) is a serious cholestatic liver disease that can be a complication of drug-induced liver injury (DILI). While journals have published case reports of this condition, large studies on a cohort of these patients are lacking. We aimed to compile published case reports and case series of patients with VBDS and DILI to describe the clinical and laboratory characteristics of the disease and identify factors associated with good and poor outcomes.
We included case reports and case series of VBDS secondary only to DILI. We extracted demographic, clinical, laboratory, treatment, and exposure data from each case report and categorized cases by outcome, good versus poor. We defined poor outcomes as cases with severe long-term complications or death. We analyzed risk factors for poor outcomes using logistic regression.
We identified a total of 59 eligible cases. Of those, 39 (59%) were female, the median age was 36 (IQR:12–58), and 18 (31%) were pediatric cases (≤18 years). The most common offending drug class was antibiotics, especially beta-lactams. Patients with increased total bilirubin (OR=4.69; 95% CI=1.55–15.49; p = 0.008), increased direct bilirubin (OR=6.50; 95% CI=1.34–48.91; p = 0.034), lower liver synthetic activity (OR=0.11; 95% CI=0.02–0.55; p = 0.013), and older age (OR=3.31; 95% CI=1.15–10.04; p = 0.029) were more likely to develop poor outcomes.
In patients with VBDS and DILI, antibiotics were the most common offending agents. Higher total and direct bilirubin levels were associated with poor outcomes.
Oral ibuprofen promoted cholestatic liver disease in very low birth weight infants with patent ductus arteriosus
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Citation Excerpt :
Furthermore, several case reports suggested that ibuprofen directly caused liver toxicity and CLD in infants and children [18–21]. Several instances of biopsy confirmed chronic vanishing bile duct syndrome, which may require liver transplantation, have been attributed to ibuprofen use [18–21]. In addition, an in vitro study established a direct relationship of ibuprofen with cholestasis [22], since the strength of the cholestasis signature obtained after treatment with ibuprofen could be directly related to the basal expression of ibuprofen metabolizing enzymes in various primary human hepatocyte sandwich cultures.
Hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) infants is routinely treated in many countries with oral ibuprofen. This study retrospectively assessed whether the risk of cholestatic liver disease (CLD) increased due to oral ibuprofen administration in VLBW infants.
A total of 122 VLBW preterm infants (26∼32 weeks, birth weight < 1500 g) diagnosed with patent ductus arteriosus (PDA) admitted to our neonatal intensive care unit (NICU) between September 2016 to August 2018 were included. Sixty-four infants were diagnosed with hs-PDA and received ibuprofen treatment. VLBW infants with PDA untreated with ibuprofen served as controls. Soybean oil and fat emulsions were routinely added to parenteral nutrition (PN). Once CLD was diagnosed, the fat emulsions were immediately replaced with multi-oil fat emulsion injections. To assess the independent association of treatment and duration of ibuprofen with CLD and duration of fasting and PN, binary logistic regression or multivariate linear regression analyses were conducted, adjusting for major confounders (birth weight, gestational age, Clinical Risk Index for Babies, and cholestasis-associated risk factors).
The duration of PN increased due to ibuprofen treatment for 6.559 days (95% CI: 1.769, 11.349; P = 0.008), and the risk of prolonged fasting (cutoff > 5 days) might have increased due to ibuprofen treatment (OR: 3.043, 95% CI: 0.965, 9.594; P = 0.057). Furthermore, CLD was influenced by ibuprofen treatment (OR: 6.730; 95% CI: 1.279, 35.41; P = 0.024), early thrombocytopenia 7 days postnatal (OR: 6.996; 95% CI: 1.769, 27.658; P = 0.004), and late onset sepsis (OR: 6.976; 95% CI: 1.561, 31.169; P = 0.011). Further analysis adjusting for cholestasis-associated risk factors revealed that CLD was influenced by the duration of ibuprofen treatment (OR: 2.864; 95% CI: 1.104, 7.422; P = 0.030), Platlets counts 7 days postnatal (OR: 0.971; 95% CI: 0.950, 0.994; P = 0.013), and duration of antibiotics (OR: 1.134; 95% CI: 1.002, 1.282; P = 0.046).
This retrospective study indicated oral ibuprofen duration-dependently increased the risk of CLD in VLBW infants with PDA, and early thrombocytopenia served as the critical risk factor.
Acute vanishing bile duct syndrome after the use of ibuprofen
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We present a case report of a 7-year-old patient who developed toxic epidermal necrolysis (TEN) and vanishing bile duct syndrome (VBDS) after oral ibuprofen intake. Acute VBDS is a rare disease with unknown aetiology, often presenting with progressive loss of the intrahepatic biliary tract. TEN is an immune complex-mediated hypersensitivity reaction involving the skin and mucosa, which is induced by drugs or infectious diseases, sometimes leading to systemic symptoms. The patient in this case report was treated with supportive care, a steroid and ursodeoxycholic acid, with complete recovery observed by the end of the 8th month. This case report suggests that ibuprofen can cause acute vanishing duct syndrome.
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Clinical and Laboratory ObservationAcute vanishing bile duct syndrome after ibuprofen therapy in a child

Abstract

Section snippets

Case Report

Discussion

Acknowledgements

Clin Liver Dis

Gastroenterology

Dig Liver Dis

Hepatology

Drug-induced prolonged cholestasis in adults: a histological semi-quantitative study demonstrating progressive ductopenia

Hepatology

Paucity of interlobular bile ducts

Semin Diagn Pathol

Vanishing bile duct syndrome

Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis

J Pediatr Gastroenterol Nutr

Vanishing bile duct syndrome temporally associated with ibuprofen use

Am J Gastroenterol

Clinical and Laboratory Observation
Acute vanishing bile duct syndrome after ibuprofen therapy in a child