Abstract
What is known and objective Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. Case summary A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. What is new and conclusion Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.
| Original language | English |
|---|---|
| Pages (from-to) | 573-576 |
| Number of pages | 4 |
| Journal | Journal of Clinical Pharmacy and Therapeutics |
| Volume | 39 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- autoimmune hepatitis
- drug-induced liver injury
- microvesicular steatosis
- synthetic oestrogen
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
- Medicine(all)
Cite this
A case of synthetic oestrogen-induced autoimmune hepatitis with microvesicular steatosis. / Morii, K.; Nishisaka, M.; Nakamura, S.; Oda, T.; Aoyama, Y.; Yamamoto, T.; Kishida, H.; Okushin, H.; Uesaka, K.
In: Journal of Clinical Pharmacy and Therapeutics, Vol. 39, No. 5, 2014, p. 573-576.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A case of synthetic oestrogen-induced autoimmune hepatitis with microvesicular steatosis
AU - Morii, K.
AU - Nishisaka, M.
AU - Nakamura, S.
AU - Oda, T.
AU - Aoyama, Y.
AU - Yamamoto, T.
AU - Kishida, H.
AU - Okushin, H.
AU - Uesaka, K.
PY - 2014
Y1 - 2014
N2 - What is known and objective Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. Case summary A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. What is new and conclusion Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.
AB - What is known and objective Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. Case summary A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. What is new and conclusion Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.
KW - autoimmune hepatitis
KW - drug-induced liver injury
KW - microvesicular steatosis
KW - synthetic oestrogen
UR - http://www.scopus.com/inward/record.url?scp=84929131824&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929131824&partnerID=8YFLogxK
U2 - 10.1111/jcpt.12191
DO - 10.1111/jcpt.12191
M3 - Article
C2 - 24989642
AN - SCOPUS:84929131824
VL - 39
SP - 573
EP - 576
JO - Journal of Clinical Pharmacy and Therapeutics
JF - Journal of Clinical Pharmacy and Therapeutics
SN - 0269-4727
IS - 5
ER -