Primary sclerosing cholangitis: A rare cause of liver dysfunction in pregnancy

Introduction

Primary sclerosing cholangitis (PSC) is a chronic progressive autoimmune condition characterised by inflammation and fibrosis of the medium and large bile ducts. It is rarely diagnosed for the first time in pregnancy. The workup of liver dysfunction in pregnancy is a complex issue. Pregnancy related causes should be considered but timing of manifestations is an important factor in determining the underlying cause. PSC is a rare condition with no available treatments that affect disease progression. The management of PSC in pregnancy requires a multidisciplinary team to optimise maternal and fetal outcomes.

Case report

A 28-year-old woman in her second ongoing pregnancy, with a history of a previous term vaginal birth, presented at 17 weeks of gestation with painless obstructive jaundice and pruritus. She had mild steatorrhoea and darkened urine but had no infective symptoms, recent travel or medical history noted at admission. Investigations showed a mixed picture of liver dysfunction, with a raised bilirubin level of 95 µmol/L. Infectious serum screening was negative. Liver ultrasound and magnetic resonance cholangiopancreatography (MRCP) were unremarkable. Fasting bile acids were 317 µmol/L (normal 0–10) and she was commenced on ursodeoxycholic acid with a presumed diagnosis of intrahepatic cholestasis of pregnancy (ICP).

Over the following six weeks, her symptoms progressed despite ursodeoxycholic acid. Blood showed an INR of 2.0 treated with intravenous vitamin K and she was readmitted for further investigation. On more detailed history, she had had a colonoscopy in 2008 for diarrhoea with a biopsy showing an active chronic colitis with a prominent plasma cell reaction suggestive of ulcerative-type colitis. She was treated at the time with mesalazine suppositories with complete resolution of symptoms.

During her second admission, MRCP was repeated and showed new smooth intrahepatic duct dilatation, suggesting PSC. A multidisciplinary meeting was conducted involving the obstetric and gastroenterology teams. Her liver function continued to slowly deteriorate and the decision was made to proceed with a liver biopsy. The results of the biopsy showed features of a chronic cholestatic disorder suggestive of a primary biliary process, with intrahepatic and canalicular cholestasis and mixed inflammatory cell infiltrate within the portal tracts with no features of autoimmune hepatitis, supportive of a diagnosis of PSC. She was commenced on cholestyramine and continued ursodeoxycholic acid.

At 28 weeks of gestation she presented with an unprovoked painless antepartum haemorrhage and her cervix was 6 cm dilated. The membranes spontaneously ruptured with thick meconium noted. There were no signs of fetal distress on continuous fetal monitoring. Labour progressed quickly and a live female infant was delivered with a birth weight of 1100 g and Apgars of 8 and 9 at 1 and 5 min respectively. The infant made good progress in the neonatal unit with no complications relating to prematurity and was discharged 10 weeks after delivery.

Postnatally, the maternal liver function stabilised initially but never improved (Figure 1). In the following months there was a slow but progressive deterioration in liver function with bilirubin increasing to over 300 µmol/L. Eleven months postpartum, she underwent a liver transplant. The native liver histopathology supported the diagnosis of PSC.

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Figure 1.

Liver function results throughout pregnancy and postpartum. GGT, gamma-glutamyl transferase; ALP alkaline phosphatase

Discussion

PSC is a chronic progressive autoimmune condition characterised by inflammation and fibrosis of the medium and large bile ducts. A significant overlap is seen with ulcerative colitis; 60–80% of people with PSC have ulcerative colitis but only a small proportion of women with ulcerative colitis have PSC. There is no therapy with proven beneficial effect on disease progression and PSC is one of the more common indications for liver transplant in Australia. Without a liver transplant, median survival is 10 to 12 years from diagnosis; with liver transplantation five-year survival rates are above 90%. ¹

There are a small number of case reports of PSC in pregnancy with fewer still of a new diagnosis in pregnancy. The largest published case series from Sweden compares 229 singleton pregnancies complicated by PSC with a large control population. The comparison highlights an increase in the risk of preterm birth, induction of labour and caesarean section. These risks persisted when adjusted for the presence or absence of inflammatory bowel disease. Only 13 (5.7%) women were diagnosed with PSC during pregnancy and only 4 pregnancies delivered before 32 weeks of gestation. The majority of preterm births in this review were iatrogenic, but a significant difference in the spontaneous preterm birth rate remained. ²

Any significant derangement of liver function should be thoroughly investigated during pregnancy. ³ Albumin may be lowered by the haemodilutional state of pregnancy and alkaline phosphatase level may be modestly increased by placental production however the remainder of tests suggested in the standard assessment of liver dysfunction should be minimally impacted by pregnancy. ⁴ Alanine aminotransferase and aspartate aminotransferase levels also decrease during normal pregnancy and hence pregnancy specific reference ranges should be used in order to appropriately detect abnormalities. ⁵ Ultrasound has a well-established safety profile and MRI can be performed, preferentially without gadolinium contrast in pregnancy, to gain extra detail of the biliary tract if required. ³

Liver biopsy is rarely performed in pregnancy but should be considered when the diagnosis is uncertain. ⁶ In a small case series of women who underwent liver biopsies during pregnancy, the most common indications were for known chronic hepatitis. ⁷ Concern regarding potential autoimmune liver disease drove the decision to proceed with liver biopsy in this case. It was hoped that the biopsy would provide a diagnosis so that a treatment could be initiated to slow the progression of the liver dysfunction and prolong the pregnancy.

There are several pregnancy-related causes of liver dysfunction, however the majority of possible diagnoses impact liver function in the second half of pregnancy. ⁴ ICP is the most common cause of cholestatic liver disease in pregnancy typically with onset during the late second and third trimester. ⁴ There are case reports of ICP occurring in first trimester, however this is very uncommon. ⁸ Bilirubin levels are rarely raised. ⁴ Imaging shows no abnormality and the liver function returns to normal shortly after delivery. Liver biopsy is not required for diagnosis however if performed shows cholestasis without inflammation and with preservation of portal tracts. ⁹

This case highlights the potential complications of PSC, particularly with the rare situation of a new diagnosis in pregnancy. Liver biopsy was performed in this case without complication to guide treatment decisions and should not be considered contraindicated in pregnancy. The multidisciplinary workup and approach to new presentation of liver dysfunction in pregnancy is vital to achieving optimal maternal and neonatal outcomes.