Propylthiouracil‐associated liver failure presenting as probable autoimmune hepatitis in a child with Graves' disease

Sipe, Walter E.B.; Su, Maureen A.; Posselt, Andrew M.; Kim, Grace; Quiros, J. Antonio; Rosenthal, Philip

doi:10.1111/j.1399-3046.2006.00487.x

Cited by 18 publications

(8 citation statements)

References 18 publications

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“…No patient presented relapse or required transplantation, and because the associated medication was suspended in all of them, no cases of hepatic failure were reported, which has been reported in the setting of AIH 24. In addition, it was possible to discontinue immunosuppression, suggesting that these patients have a better prognosis than patients with idiopathic AIH.…”

Section: Discussionmentioning

confidence: 96%

“…As in this case, PTU‐induced AIH is reported in the female population with a history of Graves’ disease 22. Unlike other forms of hepatotoxicity by PTU, this context forces the definitive discontinuation of the drug due to recurrence of the disease with reexposure23 due to the fact that there are even reports of liver failure with prolonged exposure 24…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential characteristics in drug‐induced autoimmune hepatitis

et al. 2018

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Background and AimDrug‐induced autoimmune hepatitis (DIAIH) is an adverse effect associated with several drugs that usually occurs acutely, with variable latency, and it may potentially be mortal. There are a few reports and studies about DIAIH.MethodsThis was an analytical study of a retrospective cohort of patients, discriminated according to idiopathic or drug‐induced etiology, followed up for a 7‐year period until 31 December 2016.ResultsA total of 190 patients were selected for the analysis, 12 (6.3%) with DIAIH. The two main drugs related to DIAIH were nitrofurantoin, n = 8 (67%), and NSAID, n = 2 (17%), constituting 84% of the cases. There were no significant differences in seropositivity between AIH with DIAIH in antinuclear antibodies (ANA) and anti‐smooth muscle antibodies (ASMA) antibodies, with 82.6% versus 82.6% and 34% versus 16%, respectively. The fibrosis stages were similar, except for the F4 stage, in a greater proportion in AIH. None of the patients with DIAIH had cirrhosis or developed it during follow‐up, but it was present in 42.1% of the AIH cases at diagnosis (P = 0.003). Biochemical remission with management was higher in DIAIH but not significant (91.7% vs 80.9%, P = 0.35). The definitive interruption of immunosuppression was successfully performed in 25% of those with DIAIH without relapses but was only possible in 2.8% in AIH (P < 0.001) with 32 cases of relapses.ConclusionDIAIH constitutes a minor proportion of AIH. The clinical and histological characteristics may be similar; DIAIH patients have a greater chance of having treatment suspended with a low risk of relapse, progression to cirrhosis, or need for liver transplant.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Differential characteristics in drug‐induced autoimmune hepatitis

et al. 2018

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“…She was found to have elevated ANA titers and required a liver transplant. After exclusion of all other causes, PTU was felt to be the hepatotoxic agent, resulting in autoimmune hepatitis [57].…”

Section: And Hepatotoxicitymentioning

confidence: 99%

“…Spontaneous recovery was noted in some patients with discontinuation of the drug [60]. Steroids followed by liver transplantation were required in some patients [57]. Despite adequate therapy including liver transplant and close monitoring, death has been reported in children [61].…”

Section: And Hepatotoxicitymentioning

confidence: 99%

Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity

Akmal

Kung²

2014

Expert Opinion on Drug Safety

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PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.

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“…Recovery from liver failure without transplant occurred in 18 individuals, transplantation occurred in 3 persons, and 9 deaths were reported. Of these cases, 14 were pediatric patients [8, 12, 14, 21, 22, 25, 26, 29, 31, 35, 37, 39, 41, 43] (Table 1). There were three deaths in PTU-treated pediatric patients.…”

Section: Case Reportsmentioning

confidence: 99%

Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Rivkees

Mattison

2009

International Journal of Pediatric Endocrinology

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Propylthiouracil (PTU) was introduced for clinical use in July 1947 for Graves' disease (GD) treatment. Over the 60 years that this medication has been used, reports of PTU-related liver failure and death have accumulated. On October 28, 2008, an expert panel evaluated PTU drug safety in children at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) It is estimated that about 4000 pediatric patients per year with GD are being treated with antithyroid drugs (ATDs) in the United States, and up to 30% of pediatric patients with GD are being treated with PTU. The risk of severe PTU-induced liver failure is estimated as 1 in 2000–4000 children. The number of children developing reversible PTU-induced liver injury is estimated to be at least 1 in 200. Routine biochemical surveillance of liver function and hepatocellular integrity is not useful in identifying children who will develop liver failure. Children appear to be at higher risk for PTU-induced liver injury than adults. PTU should not be used as first line therapy for the treatment of GD in children. Current PTU use in children taking this medication should be stopped in favor of alternate therapies.

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Propylthiouracil‐associated liver failure presenting as probable autoimmune hepatitis in a child with Graves' disease

Cited by 18 publications

References 18 publications

Differential characteristics in drug‐induced autoimmune hepatitis

Differential characteristics in drug‐induced autoimmune hepatitis

Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity

Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

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