Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923002823 |
| _version_ | 1827378180613210112 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Jeremy S. Nayagam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:52:14Z |
| format | Article |
| id | doaj.art-42a14995d75e44aeb0e9eb445b2468cb |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-08T12:52:14Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-42a14995d75e44aeb0e9eb445b2468cb2024-01-20T04:46:20ZengElsevierJHEP Reports2589-55592024-01-0161100951Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitisJeremy S. Nayagam0Tobias J. Weismüller1Piotr Milkiewicz2Karolina M. Wronka3Emil Bik4Christoph Schramm5Katja Fuessel6Taotao Zhou7Johannes Chang8Martti Färkkilä9Ylva Carlsson10Anastasia Lundman11Nora Cazzagon12Giorgia Corrà13Eirini Rigopoulou14George N. Dalekos15Aiva Lundberg Båve16Annika Bergquist17Karim Ben Belkacem18Marco Marzioni19Martina Mancinelli20Xavier Verhelst21Hanns-Ulrich Marschall22Michael A. Heneghan23Deepak Joshi24Institute 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.Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; Department of Internal Medicine - Gastroenterology and Oncology, Vivantes-Humboldt-Klinikum, Berlin, GermanyLiver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland; Translational Medicine Group, Pomeranian Medical University, Szczecin, PolandLiver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, PolandLiver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland. 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. Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyEuropean Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, FinlandDepartment of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, SwedenEuropean 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, ItalyEuropean 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, ItalyDepartment of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, GreeceEuropean 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, GreeceDepartment of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenReference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Saint-Antoine Hospital, Assistance Publique-Hôpitaux De Paris, Paris, FranceClinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti University Hospital, Ancona, ItalyClinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti University Hospital, Ancona, ItalyEuropean Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, BelgiumEuropean 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, SwedenDepartment of Inflammation Biology, King’s College London, London, UK; European Reference Network for Hepatological Diseases (ERN RARE-LIVER), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Liver Studies, King’s College Hospital, London, UK; Department of Inflammation Biology, King’s College London, London, UKBackground & 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.http://www.sciencedirect.com/science/article/pii/S2589555923002823Primary sclerosing cholangitisIntrahepatic cholestasis of pregnancyCholangiopathyPruritusUrsodeoxycholic acidBile acids |
| spellingShingle | 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 Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis JHEP Reports Primary sclerosing cholangitis Intrahepatic cholestasis of pregnancy Cholangiopathy Pruritus Ursodeoxycholic acid Bile acids |
| title | Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis |
| title_full | Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis |
| title_fullStr | Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis |
| title_full_unstemmed | Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis |
| title_short | Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis |
| title_sort | maternal liver related symptoms during pregnancy in primary sclerosing cholangitis |
| topic | Primary sclerosing cholangitis Intrahepatic cholestasis of pregnancy Cholangiopathy Pruritus Ursodeoxycholic acid Bile acids |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923002823 |
| work_keys_str_mv | AT jeremysnayagam maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT tobiasjweismuller maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT piotrmilkiewicz maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT karolinamwronka maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT emilbik maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT christophschramm maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT katjafuessel maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT taotaozhou maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT johanneschang maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT marttifarkkila maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT ylvacarlsson maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT anastasialundman maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT noracazzagon maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT giorgiacorra maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT eirinirigopoulou maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT georgendalekos maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT aivalundbergbave maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT annikabergquist maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT karimbenbelkacem maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT marcomarzioni maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT martinamancinelli maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT xavierverhelst maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT hannsulrichmarschall maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT michaelaheneghan maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis AT deepakjoshi maternalliverrelatedsymptomsduringpregnancyinprimarysclerosingcholangitis |