E
K Tan1, J L Gibson2, A Gallagher3
1Queen Mother’s Hospital Dalnair Road Glasgow G3 8SH
2Southern General Hospital, Department of O & G, Glasgow G51 4TF
3Victoria Infirmary, Langside Road, Glasgow, G42 9TZ
Communicating address: 3 Netherton Avenue Flat 1 / 2 Glasgow G13 1BQ
Email (Corresponding Author): dr.ektan@gmail.com
Case
Report
A 22-year-old para 1 attended for antenatal care in her second pregnancy. Her past medical history included idiopathic adult ductopenia and oesophageal varices.
In her first pregnancy 2 years ago, she unfortunately had an intrauterine death at 34 weeks. Fresh meconium was noted at caesarean delivery under general anaesthesia, but post mortem of the foetus revealed no anomalies.
In her current pregnancy, she first presented to the medical obstetrics clinic at 18 weeks. Investigations at this time revealed a platelet count of 74, normal LFTs but raised bile acids of 88umol/l. Her pre-existing medication prior to pregnancy included propanolol, ursodeoxycholic acid, thiamine and questran sachets. She was advised strongly to comply and continue with these medications. Detailed anomaly scan at 20 weeks was normal.
As a result of the raised bile acid levels at her initial visit, ursodeoxycholic acid was increased from 1g to 1.5g per day. In addition, she was also prescribed multivitamins. Despite the raised doses of ursodeoxycholic acid, bile acids rose to 157umol/l at 24 weeks, 144umol/l at 28 weeks and 253umol/l at 30 weeks. It was however better as pregnancy progressed, and LFTs remained within normal ranges during pregnancy. Growth scans at 24, 26, 29 and 31 weeks confirmed normal growth and liquor.
Vitamin K 20mg od was prescribed from 28 weeks. Antenatal steroids were administered at 31 weeks, and a planned caesarean section was performed at 32 weeks under spinal anaesthetic. A healthy boy weighing 1.30 kg was delivered. Postpartum, the ursodeoxycholic acid was reduced to pre pregnancy doses; she opted for implanon contraceptive post delivery.
Discussion
Idiopathic Adult Ductopenia (IAD) is a rare liver condition first described by Ledwig et al in 1988. 1 In this condition with an unknown cause, there is a loss of the interlobular bile ducts in the liver. 1 As a result of this loss of interlobular and septal bile ducts (more than 50% destruction), patients with IAD present with pruritis and jaundice, due to persistently raised bile acids. 2 Liver function tests (gamma-glutamyltransferase and alanine aminotransferase enzymes) tend to be deranged. 3 In addition, patients with IAD have a wide spectrum of disease severity, ranging from mild disease with minimal symptoms to severe liver disease with extensive biliary cirrhosis requiring liver transplantation 3 . Patients normally have a mean age of 41 (range 27-57) 3 , and so patient AA was very young to be diagnosed with this condition.
Although obstetric cholestasis during pregnancy is not uncommon, the management of a pregnant woman with cholestasis due to pre-existing IAD is rare, and has never been reported. Many of our interventions in AA’s case were based upon guidance from our gastro-enterologist colleagues and our pre-existing knowledge on obstetric cholestasis.
In our patient, the diagnosis of IAD was made prior to her first pregnancy, when she presented with pruritis and haematemesis due to oesophageal varices. The diagnosis of IAD was confirmed on a liver biopsy, which revealed extensive destruction of interlobular and septal bile ducts. Screening tests for other conditions (hepatitis and other viral infection serology, autoimmune screen for primary biliary cirrhosis and chronic active hepatitis) causing intrahepatic biliary destruction were negative. As a result of her condition, she was prescribed several medications. Propanolol, a beta blocker, has the beneficial effect of lowering portal blood pressure, thereby reducing the risk of bleeding from oesophageal varices 4 . Ursodeoxycholic acid, a naturally occurring bile acid, is useful in the symptomatic relief of pruritis by increasing the rate of bile flow from hepatocytes, and also enhances bile acid clearance across the placenta from the fetus; it is commonly used in obstetric cholestasis. 5 Questran (cholestyramine), a bile acid sequestrant, binds bile acid in the gastrointestinal tract to prevent its absorption, forming insoluble complexes excreted in faeces. 6
Elevated bile acids in pregnant women with obstetric cholestasis can have detrimental toxic effects on the fetus and result in intrauterine death. 7 In her first pregnancy, she failed to comply with her medication and stopped her ursodeoxycholic acid at 12 weeks because of fears that the drug might harm her baby. This could have contributed to the intrauterine death and fresh meconium stillbirth at 34 weeks. She was delivered by caesarean section under general anaesthesia because of concerns that the raised thoracic and intra abdominal pressure that can occur due to active pushing and repeated valsalva manoeuvres during the 2nd stage of labour could increase the risks of life threatening haematemesis from oesophageal varices.
In her current pregnancy, she was reviewed regularly. The importance of compliance with her treatment was explained. Because propanolol, a beta blocker used to reduce portal hypertension, might affect placental circulation and cause growth restriction, fetal growth was monitored regularly during pregnancy by ultrasound. 8 The BNF recommends caution with cholestyramine during pregnancy, but the benefits of normalising bile acids levels during pregnancy with ursodeoxycholic acid and cholestyramine outweigh any possible risks to the fetus. Although ursodeoxycholic acid is generally more effective in normalising bile acids in obstetric cholestasis and has a safer fetal profile than cholestyramine, cholestyramine was prescribed in our case as ursodeoxycholic acid failed to normalise the bile acid levels despite high doses. 9 Because cholestyramine can affect the absorption of fat soluble vitamins, she was advised to take multivitamins supplements during pregnancy. In addition, vitamin K was prescribed orally towards the last 4 weeks of her pregnancy to reduce the risks of post partum haemorrhage and neonatal intracranial bleed. 10
Despite the increasing dose of ursodeoxycholic acid during pregnancy, her bile acid levels continue to rise. However, her liver function tests remain normal during pregnancy. An elective caesarean section at 32 weeks was planned in view of her previous history of stillbirth at 34 weeks and the persistently raised bile acids with therefore the ongoing risks of fetal intrauterine death. A spinal anaesthetic was administered with caution, as hypotension can cause nauseas sensation and vomiting, and too forceful vomiting might result in oesophageal varices haemorrhage. Anti emetics were prescribed as a prophylactic measure. In addition, sengstaken blakemore tubes were ordered for the obstetric theatres, in case they were required to control oesophageal varices bleeding. Fortunately, the caesarean delivery was uneventful.
Post delivery, implanon (progesterone implant) was considered as an effective and safe contraception. Hormonal contraception containing oestrogen is generally avoided because of effects on the liver. However, in women with mild liver cirrhosis, the benefits of using progestogen-only contraceptives generally outweigh the risks (WHO Medical Eligibility Criteria for Contraceptive Use Category 2). 11
In summary, idiopathic adult ductopenia is a rare liver condition characterised by persistent cholestasis due to the loss of interlobar bile ducts. Multidisciplinary input between the obstetricians, gastroenterologists and anaesthetists is required in the care of pregnant woman with this condition.
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