Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis
Jeremy S. Nayagam,
Tobias J. Weismüller,
Piotr Milkiewicz,
Karolina M. Wronka,
Emil Bik,
Christoph Schramm,
Katja Fuessel,
Taotao Zhou,
Johannes Chang,
Martti Färkkilä,
Ylva Carlsson,
Anastasia Lundman,
Nora Cazzagon,
Giorgia Corrà,
Eirini Rigopoulou,
George N. Dalekos,
Aiva Lundberg Båve,
Annika Bergquist,
Karim Ben Belkacem,
Marco Marzioni,
Martina Mancinelli,
Xavier Verhelst,
Hanns-Ulrich Marschall,
Michael A. Heneghan,
Deepak Joshi
Affiliations
Jeremy S. Nayagam
Institute of Liver Studies, King’s College Hospital, London, UK; Department of Inflammation Biology, King’s College London, London, UK; Corresponding author. Address: Institute of Liver Studies, King’s College Hospital, London, UK. Tel: +44-203-299-3369.
Tobias J. Weismüller
Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; Department of Internal Medicine - Gastroenterology and Oncology, Vivantes-Humboldt-Klinikum, Berlin, Germany
Piotr Milkiewicz
Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland; Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland
Karolina M. Wronka
Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
Emil Bik
Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
Christoph Schramm
. Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Katja Fuessel
. Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Taotao Zhou
Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Johannes Chang
Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Martti Färkkilä
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
Ylva Carlsson
Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Anastasia Lundman
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
Nora Cazzagon
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Unit of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, Padova, Italy
Giorgia Corrà
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Unit of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, Padova, Italy
Eirini Rigopoulou
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
George N. Dalekos
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
Aiva Lundberg Båve
Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Annika Bergquist
Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Karim Ben Belkacem
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Saint-Antoine Hospital, Assistance Publique-Hôpitaux De Paris, Paris, France
Marco Marzioni
Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti University Hospital, Ancona, Italy
Martina Mancinelli
Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti University Hospital, Ancona, Italy
Xavier Verhelst
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
Hanns-Ulrich Marschall
European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
Michael A. Heneghan
Department of Inflammation Biology, King’s College London, London, UK; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Deepak Joshi
Institute of Liver Studies, King’s College Hospital, London, UK; Department of Inflammation Biology, King’s College London, London, UK
Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.
