Chronic cholestatic liver disease and pregnancy - rare
conditions but not to be confused with intrahepatic cholestasis of
pregnancy
Gunilla Ajne
Department of Obstetrics and Gynaecology, CLINTEC, Karolinska Institute,
Karolinska University Hospital, Stockholm, Sweden
E-mail: gunilla.ajne@sll.se
Chronic cholestatic liver disease and pregnancy is rare as time for
diagnosis peaks after reproductive years or late reproductive years. As
a consequence, studies are few in this topic. M.Cauldwell and colleagues
report maternal and fetal outcome in a retrospective case series of 61
pregnant women with primary biliary cholangitis or primary sclerosing
cholangitis (BJOG 2020 xxxx). The collected time span is 20 years
including ten different centres, reflecting the relatively rare
conditions during pregnancy. As a consequence, the built-in variations
of monitoring, treatment and care are considerable. So far, there is no
published consensus guideline on how to monitor and care for pregnant
women with these progressive autoimmune liver disorders, from mild
disease or to affected liver function with cirrhosis. The current study
concludes continuous use of ursodeoxycholic acid (UDCA) during pregnancy
and awareness of the risk for preterm birth, that was associated with
peak serum alaninaminotransferase at booking and peak maternal serum
bile acid during pregnancy. Pregnancy was well tolerated in this case
series of selected population with a probable overweight of mild to
moderate cases.
During the last decade, an increasing number of studies have been
published regarding intrahepatic cholestasis of pregnancy (ICP),
maternal peak bile acid and pregnancy outcome. A recent meta-analysis
(Ovadia et al, Lancet 2019;393:899-909)) demonstrates a risk for
stillbirth in ICP with maternal peak bile acid concentrations at or
above 100 µmol/L and risk for preterm birth at or above 40 µmol/L. With
current knowledge, there is no obvious reason to believe that maternal
bile acids in pregnant women with PBC or PSC will affect fetal pregnancy
outcome differently. The UK PITCHES trial (Chapel et al, Lancet
2019;394:840-860) could not show an amelioration in maternal bile acid
levels with UDCA treatment in ICP. A probable explanation may be a total
bile acid enrichment with the treatment. If this is true also for
patient with chronic cholestatic liver disease with long-term treatment
with UDCA and pregnancy has to be explored. Attention is also
recommended towards the variations in measurements of bile acid
concentration in different studies and comparisons. There is an obvious
mixture of fasting and post-prandial samples, with or without treatment
with UDCA.
PBC, PSC and associated inflammatory bowel disease may need additional
treatment with immunosuppressive drugs, such as azatioprin, with known
but less common side effects such as cholestatis. An increased demand on
the metabolism of estrogens and progesterone during pregnancy might
hypothetically induce such side effects. Additional treatments have to
be reported in more detail for future studies. Further, there is an
ongoing discussion regarding severe early cases of ICP and benefit of
treatment. Criteria for ICP is exclusion of other liver diseases
presenting with same symptoms and biomarkers (such as PBC, PSC and
chronic hepatitis C) and disappearance of pruritus and elevated liver
tests postpartum. One might speculate that early severe ICP may mimic
early signs of chronic liver diseases with pregnancy acting as a stress
test for the liver. A situation that may be rare, but obstetricians have
to pay attention to. Delayed diagnosis and inadequate follow-up or
treatment dose not benefit the patient, but increased knowledge does.
Finally, only 34 per cent had evidence of preconception counselling in
the study by M.Caudwell et al. Let us hope that we with time realise the
importance of preconception counselling for all women with a significant
chronic disease.
Disclosure of interest: None declared. A completed disclosure
of interest form is available to view online as supporting information.