Title: Obstetric Cholestasis Presenting With Unusually High Levels Of Serum Transaminases

Dr Kiran Popli (Specialist Registrar, Obstetrics and Gynaecology) James Cook University Hospital Marton Road, Middlesbrough TS4 3BW  

Dr Judith Roberts (Consultant Obstetrician and Gynaecologist) The Queen Mother’s Hospital Dalnair Street Glasgow G3 8SJ                  

Dr Peter R. Mills (Consultant Gastroenterologist) Gartnavel General Hospital 1053 Great Western Road Glasgow G12 0YN

Corresponding AuthorKIRAN POPLI 26, Bamburgh House Marton Road Middlesbrough TS4 3SR Telephone: 00447984828645 

E-mail: kiran_popli@hotmail.com

SMJ 2006 51(1): 57

 

Abstract

Obstetric cholestasis is typically suspected when a pregnant woman presents with generalized pruritus without a rash. Biochemically, only a mild abnormality of liver function tests is seen without any systemic signs and symptoms. The patient is usually treated with Ursodeoxycholic acid which improves both pruritus and liver function tests. We present a case where a pregnant woman presented with pruritus and was found to have unusually high levels of serum transaminases. The diagnosis of obstetric cholestasis was made only by exclusion of other causes of hepato-biliary dysfunction. Fortunately the condition responded well to the standard treatment and both mum and baby had a favourable outcome.

Key words

Obstetric cholestasis, serum transaminases, Ursodeoxycholic acid


Introduction

Obstetric cholestasis was once considered a rare disorder but as the awareness of this condition is increasing, the incidence seems to be rising as well. Currently this varies between 0.1% to 1.5% of pregnancies in Europe and 9.2% to 15.6% in South American countries such as Bolivia and Chile1. The diagnosis is usually suspected clinically based on pruritus in the absence of a rash in the 3rd trimester of pregnancy. The liver function tests may be suggestive of cholestasis although there is no uniform agreement on the criteria for diagnosis. Knox and Olans2 assert that serum transaminases may be elevated 2-10 fold or greater, bilirubin may be up to 6 mg/dl and alkaline phosphatase may be elevated 4 fold. Palma et al3 suggest that the most sensitive laboratory abnormality is the measurement of total serum bile acids. This is often the first and may be the only biochemical abnormality. In contrast Davies et al4 assert that serum alanine aminotransferase (ALT) is the most sensitive of the conventional liver tests. However it is generally agreed that if serum ALT levels are >200 IU or signs and symptoms like jaundice, fever, malaise, epigastric or hypochondrium pain are present, then other hepato-biliary pathologies like viral hepatitis, gallstones or autoimmune liver diseases are more likely. Here we present a case of obstetric cholestasis with unusually high levels of serum transaminases that correlated poorly with levels of serum bilirubin and alkaline phosphatase.

 

Case- Report

A 30 yrs. old primigravida attended the antenatal clinic at 31 weeks gestation complaining of pruritus during the preceding week. The pruritus was generalized but particularly noticeable in palms and soles and worse at night. There was no history of darkening of urine or lightening of stools and there were no complaints of abdominal pain, fever, malaise, nausea, vomiting or any skin rash. She gave no history of liver disease, needle stick injury or blood transfusion and she had had previous negative hepatitis B serology. She had no family history of liver diseases and was not on any medications apart from iron tablets. 

Physical examination was unremarkable with no jaundice or other signs of chronic liver disease. The B.P. was 130/80 mmHg. The uterus was consistent with the gestational age and foetal heart sounds were heard. Routine laboratory studies showed a normal haematocrit of 40%, white blood cell count of 7,300/ml and a platelet count of 200,000/ml. The serum transaminases (ALT and AST) were raised but the levels of serum bilirubin and alkaline phosphatase were normal as shown in table 1. Urinalysis was negative for bilirubin, glucose, proteins or ketones. Over the next few days, serum trasnsaminases increased further and pruritus worsened without the appearance of any other symptoms. Ultrasound examination of the upper abdomen did not reveal any gallstones. There was no focal lesion in the liver or any evidence of intra-hepatic biliary dilatation. Prothrombin time and APTT were normal. IgM anti-HAV, HBsAg, IgM anti HB core and anti-HCV were all negative and serology for Cytomegalovirus, Epstein Barr virus, herpes virus and toxoplasmosis were normal. Anti-nuclear, anti-smooth muscle and anti-mitochondrial antibodies were absent.

In view of the above results, a diagnosis of obstetric cholestasis was considered most probable inspite of markedly elevated transaminase levels. She was managed as an in-patient and was commenced on Ursodeoxycholic acid (UDCA)   250 mg three times a day. She was also given betamethasone injections to enhance fetal lung maturity (incase she required to be delivered prematurely) and vitamin K tablets to prevent obstetric haemorrhage and haemolytic disease of the new born. Fetal surveillance was performed at regular intervals with cardiotocography, doppler and scans to confirm fetal wellbeing and appropriate growth. Within 24 hours of starting UDCA, her pruritus improved dramatically and transaminases levels began to fall over the next few days (table 1). Labour was induced at 35+ weeks and she had vaginal delivery of a healthy baby girl weighing 2.5Kg. UDCA was stopped following delivery and she had an uncomplicated post- partum period. On follow-up at 6 weeks, she was asymptomatic with normal liver function tests.

 

Discussion

Although this case had many classic features of obstetric cholestasis (for example onset of pruritus late in pregnancy, absence of rash and resolution of symptoms and biochemistry with UDCA), it was unusual with respect to the level of serum transaminases that were extremely high. Also, the alkaline phosphatase and serum bilirubin levels are expected to be elevated (although modestly) in obstetric cholestasis, these were within normal limits in this case. Serum bile acids are considered to be very sensitive indicators of obstetric cholestasis, but these were not performed, as these tests were not locally available. Also these tests are more important when a woman is symptomatic with pruritus but standard liver function tests are normal. This is because the rise in bile acids usually precedes the rise in transaminases and may be the only indicator of cholestasis.

 

These extremely high levels of transaminases (30 times the normal levels for ALT and 15 times for AST) raised the question of viral hepatitis, as the levels are usually only moderately elevated (2-3 fold) in obstetric cholestasis5, 6. Serology for viral hepatitis was negative (hepatitis A, B and C) and there were no constitutional symptoms. Also there was rapid resolution of symptoms with UDCA. The clinical picture was not suggestive of the HELLP syndrome as there was no evidence of haemolysis, the platelet count was normal and the patient was normotensive with no demonstrable proteinuria. Primary biliary cirrhosis can present as pruritus in pregnancy but with this condition, elevation in alkaline phosphatase levels along with presence of anti-mitochondrial antibodies would be expected.

 

UDCA, an exogenous bile acid, is increasingly being used (8-12 mg/kg in 2-3 daily divided doses) in cholestasis of pregnancy although is not yet licensed for this indication7. In clinical studies it has improved both pruritus and liver function and this indeed was the case in our patient. Obstetric cholestasis is known to be associated with preterm labour in up to 60%, foetal distress in up to 33% and unexplained sudden intrauterine death in up to 2% of pregnancies1. Delivery is therefore normally planned for 37-38 weeks gestation. It was elected to deliver the baby even sooner in this case because of unusually high levels of transaminases.

 

Our aim of reporting this case is to make obstetricians and gastroenterologists aware of the possibility that markedly elevated serum transaminases may be a feature of obstetric cholestasis, and to show that with UDCA treatment the maternal symptoms and biochemistry may respond rapidly.


References

  1. Milkiewiez P, Elias E, Williamson CW, Weaver J. Obstetric cholestasis : May have serious consequences for the fetus, and needs to be taken seriously. BMJ 2002; 324: 123-124

  2. Knox TA, Olans LB. Liver disease in pregnancy. N Eng J Med 1996; 335: 569-576

  3. Palma J, Reyes H, Ribalta J et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy. A randomized, double blind study controlled with placebo. J Hepatol 1997; 27:1022-1028

  4. Davies MH, De Silva RCMA, Jones SR et al. Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid. Gut 1995; 37: 580-584

  5. Clark TJ, Dwarkanath L, Weaver JB. Pruritus in pregnancy and obstetric cholestasis. Hosp Med 1999; 60: 254-260

  6. Kelly A, Nelson-Piercy C. Obstetric Cholestasis. London: PACE Reviews, Questions and Answers. RCOG press; 2003; 3: 48-49

  7. Nelson-Piercy C. Handbook of Obstetric Medicine. Second Edition. Martin Dunitz Ltd; 2002 ;204-209

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