Rare metabolic liver diseases, coagulation and hepatocellular carcinoma – Stål and Wahlin research group

Our group has a focus on metabolic and inflammatory liver diseases, and liver cancer. We perform clinical and translational studies on hereditary hemochromatosis, porphyric liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cholangitis and hepatocellular carcinoma.

Part of the Department of Medicine, Huddinge

About our research

By using data from well characterized clinical patient cohorts, we can combine outcome data with findings from tissue analyses. We perform systematic biobanking of liver tissue, DNA and plasma, and have unique possibilities to study long-term prognosis and pathogenetic mechanisms of liver diseases. We also perform investigator-initiated prospective clinical trials on porphyria, non-alcoholic fatty liver disease and hemostasis in cirrhosis.

We have a large network of partners in both basic and clinical research departments, and we have access to advanced techniques for translational studies. Our prospective studies aim to find diagnostic and prognostic biomarkers of liver disease and liver cancer development, and to evaluate new treatments. Ultimately, we aspire to improve care for patients with liver disease.

The group is part of the Gastroenterology and Rheumatology Unit at the Department of Medicine, Huddinge (MedH).

Keywords

Autoimmune hepatitis, Primary Biliary Cholangitis, Porphyric liver diseases, NAFLD; hereditary hemochromatosis, hepatocellular carcinoma (HCC)

Collaborations

  1. SweHep national study group (BIGMAP study and PBC in Sweden)
  2. Myriam Aouadi at the Center for Infectious Medicine, and Mikael Rydén at MedH, Endocrinology Unit (The MacinNASH study)
  3. Charlotte Thålin at KI Danderyds hospital and Maria Magnusson at the Coagulation Unit (Hemostasis in liver cirrhosis - HELICS).
  4. Anna Passetto, Dept of Laboratory Medicine, (Characterization of circulating neo-antigens recognized by PD-1+ lymphocytes in hepatocellular carcinoma)
  5. Mikael Björnstedt, Unit of Pathology, and prof. Hugh Salter, Anocca AB, (Micro-RNA pattern in liver tissue as a prognostic marker in HCC)
  6. Daniel Hagey at Dept. of Laboratory medicine (Dynamic profiling of vesicle-borne RNA in HCC).
  7. Jochen Schwenk at SciLifeLab (Protein plasma biomarkers in HCC)
  8. Torkel Brismar at the radiology department (TREND study).
  9. Eliane Sardh at Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases (CMMS) (Cancer and comorbidity in acute hepatic porphyria)
  10. Cumali Efe at Harran University Hospital, Turkey and multinational collaborators (Clinical studies om autoimmune liver diseases)

Projects

1. Biomarkers in hepatocellular carcinoma (HCC) 

The aim of the project is to develop panels of serum proteins, micro-RNAs or vesicle-borne mRNAs as biomarkers for early diagnosis or prognostication of HCC.
Collaborations: Jochen Schwenk (SciLifeLab in Solna), Hugh Salter (Anocca AB), Mikael Björnstedt (Dept of Pathology), Daniel Hagey (Dept of Laboratory Medicine).
Funding: Cancerfonden, CIMED and Region Stockholm

2. Role of liver macrophage populations in the development of non-alcoholic steatohepatitis - NASH (MacinNASH)

The aim of the project is to define a subpopulation of macrophages in NASH with a gene expression profile that initiates fibrosis (scarring of the liver).
Collaborations: Myriam Aouadi (Center for Infectious Medicine).
Funding: European Research Council.

3. Biochemical, clinical, and genetic markers for prognostication in liver cirrhosis (BIGMAP)

The aim of the project is to create a national biobank for future biomarker evaluations for prognostication of liver-related events.
Collaborations: The SweHep research network. The biobank is linked to the Swedish Register for Liver Cirrhosis.
Funding: Swedish Cancer Society.

4. Hemostasis in liver cirrhosis (HELICS)

The aim of the project is to evaluate new methods for hemostasis assessment in patients with liver cirrhosis or HCC.
Collaborations: Maria Magnusson (Coagulation Unit) and Charlotte Gran (Dept of Molecular Medicine and Surgery) KI.
Funding: Region Stockholm.

5. Characterization of circulating neo-antigens recognized by PD-1+ lymphocytes in HCC (CHANNEL)

The aim of the project is to assess if neoantigens in circulating cell free DNA (cfDNA) can be recognized by PD-1+ lymphocytes.
Collaborations: Anna Pasetto (Dept. of Laboratory Medicine).
Funding: Swedish Cancer Society.

6. Hepatopathy, cancer and comorbidity in acute hepatic porphyria

The aim of the project is to characterize risks and mechanisms of long-term complications.
Collaborations: Eliane Sardh, CMMS.
Funding: Region Stockholm, CIMED & Alnylam

7. Clinical research on autoimmune liver diseases

Collaborations: Cumali Efe and multinational network of hepatologists, The SweHep research network.
Funding: Bent Ihre Foundation

Publications

  1. Treatment of non-alcoholic fatty liver disease with intermittent calorie restriction vs. low-carb high-fat diet – a randomized controlled trial.
    Holmer M, Lindqvist C, Petersson S, Moshtaghi-Svensson J, Tillander V, Brismar TB, Hagström H, Stål P. JHep Reports 2021 Feb 17;3(3):100256. doi: 10.1016/j.jhepr.2021.100256. PMID: 33898960.
     
  2. Morbidity, risk of cancer and mortality in 3,645 HFE mutations carriers.
    Hagström H, Ndegwa N, Ekstedt M, Posserud I, Rorsman F, Nyhlin N, Klintman D, Werner M, Marschall H-U, Jalmeus M, Askling J, Stål P. Liver International 2021 41(3):545-553. PMID: 33450138.
     
  3. Liver Transplantation for Acute Intermittent Porphyria.
    Lissing M, Nowak G, Adam R, Karam V, Boyd A, Gouya L, Meersseman W, Melum  Ołdakowska-Jedynak U, Reiter FP, Colmenero J, Sanchez R, Herden U, Langendonk J, Ventura P, Isoniemi H, Boillot O, Braun F, Perrodin S, Mowlem E, Wahlin S; European Liver and Intestine Transplant Association. Liver Transpl. 2021 Apr;27(4):491-501. PMID: 33259654
     
  4. Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.
    Efe C, Torgutalp M, Henriksson I, Alalkim F, Lytvyak E, Trivedi H, Eren F, Fischer J, Chayanupatkul M, Coppo C, Purnak T, Muratori L, Werner M, Muratori P, Rorsman F, Onnerhag K, Nilsson E, Heurgué-Berlot A, Demir N, Semela D, Kıyıcı M, Schiano TD, Montano-Loza AJ, Berg T, Ozaslan E, Yoshida EM, Bonder A, Marschall HU, Beretta-Piccoli BT, Wahlin S. J Gastroenterol Hepatol. 2021 Apr;36(4):936-942. PMID: 32790935.
     
  5. Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.
    Efe C, Dhanasekaran R, Lammert C, Ebik B, Higuera-de la Tijera F, Aloman C, Rıza Calışkan A, Peralta M, Gerussi A, Massoumi H, Catana AM, Torgutalp M, Purnak T, Rigamonti C, Gomez Aldana AJ, Khakoo N, Kacmaz H, Nazal L, Frager S, Demir N, Irak K, Ellik ZM, Balaban Y, Atay K, Eren F, Cristoferi L, Batıbay E, Urzua Á, Snijders R, Kıyıcı M, Akyıldız M, Ekin N, Carr RM, Harputluoğlu M, Hatemi I, Mendizabal M, Silva M, Idilman R, Silveira M, Drenth JPH, Assis DN, Björnsson E, Boyer JL, Invernizzi P, Levy C, Schiano TD, Ridruejo E, Wahlin S. Hepatology. 2021 Jun;73(6):2099-2109. doi: 10.1002/hep.31797. Erratum in: Hepatology. 2021 Dec 8; PMID: 33713486
     
  6. Energy expenditure early after liver transplantation: Better measured than predicted.Lindqvist C, Nordstedt P, Nowak G, Slinde F, Majeed A, Bottai M, Wahlin S. Nutrition. 2020 Nov-Dec;79-80:110817. PMID: 32653820.
     
  7. Comparison of lipiodol infusion and drug-eluting beads transarterial chemoembolization of hepatocellular carcinoma in a real-life setting.
    Karalli A, Teiler J, Haji M, Seth E, Brismar TB, Wahlin S, Axelsson R, Stål P. Scand J Gastroenterol. 2019 Jul;54(7):905-912. PMID: 31287338
     
  8. Characteristics and outcome of hepatocellular carcinoma in patients with NAFLD without cirrhosis.
    Bengtsson B, Stål P, Wahlin S, Björkström NK, Hagström H. Liver Int. 2019 Jun;39(6):1098-1108. PMID: 30829446
     
  9. Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
    Efe C, Taşçilar K, Henriksson I, Lytvyak E, Alalkim F, Trivedi H, Eren F, Eliasson J, Beretta-Piccoli BT, Fischer J, Calişkan AR, Chayanupatkul M, Coppo C, Ytting H, Purnak T, Muratori L, Werner M, Muratori P, Rorsman F, Önnerhag K, Günşar F, Nilsson E, Heurgué-Berlot A, Güzelbulut F, Demir N, Gönen C, Semela D, Aladağ M, Kiyici M, Schiano TD, Montano-Loza AJ, Berg T, Ozaslan E, Yoshida EM, Bonder A, Marschall HU, Wahlin S. . Am J Gastroenterol. 2019 Jul;114(7):1101-1108. PMID: 31241547.
     
  10. Quality of life as a prognostic factor for survival in hepatocellular carcinoma.
    Sternby Eilard M, Hagström H, Mortensen KE, Wilsgaard T, Vagnildhaug OM, Dajani O, Stål P, Rizell M. Liver Int. 2018;38:885-894. PMID: 28941130

Funding

  • The Swedish Cancer Society
  • Region Stockholm
  • Center for Innovative Medicine (CIMED)
  • Bent Ihre Foundation
  • Alnylam

Staff and contact

Group leader

All members of the group