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1. Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing

Author

Craig, Amanda J., Silveira, Maruhen A. Datsch, Ma, Lichun, Revsine, Mahler, Wang, Limin, Heinrich, Sophia, Rae, Zachary, Ruchinskas, Allison, Dadkhah, Kimia, Do, Whitney, Behrens, Shay, Mehrabadi, Farid R., Dominguez, Dana A., Forgues, Marshonna, Budhu, Anuradha, Chaisaingmongkol, Jittiporn, Hernandez, Jonathan M., Davis, Jeremy L., Tran, Bao, Marquardt, Jens U., Ruchirawat, Mathuros, Kelly, Michael, Greten, Tim F., and Wang, Xin W.

Published
2023
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2. THU-457 Outcome of liver transplantation in patients with hepatocellular carcinoma previously treated with immune checkpoint inhibitorbased therapy-first results from an international multicenter registry

Author

Bauer, Ulrike, primary, Ben Khaled, Najib, additional, Grottenthaler, Julia M., additional, Foerster, Friedrich, additional, Blümel, Sena, additional, Heinrich, Sophia, additional, Sinner, Friedrich, additional, Venerito, Marino, additional, Taubert, Richard, additional, Kremer, Andreas E., additional, Weinmann, Arndt, additional, Berg, Christoph P., additional, Lange, Christian M., additional, de Toni, Enrico, additional, Schmid, Roland M., additional, and Ehmer, Ursula, additional

Published
2024
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4. Lower uromodulin serum levels are associated with poorer prognosis in patients with cirrhosis and hepatorenal syndrome type 2.

Author

Schleicher, Eva Maria, Gairing, Simon Johannes, Castven, Darko, Hock, Charlotte Sophie, Dobbermann, Henrike, Heinrich, Sophia, Meineck, Myriam, Kaps, Leonard, Galle, Peter Robert, Weinmann-Menke, Julia, Nguyen-Tat, Marc, Marquardt, Jens U., and Labenz, Christian

Subjects
HEPATORENAL syndrome, UROMODULIN, ACUTE kidney failure, CIRRHOSIS of the liver, PROGNOSIS
Abstract

Hepatorenal syndrome (HRS) is associated with a dismal prognosis in patients with cirrhosis, and therapeutic options are limited. Biomarkers to identify patients with poor response to therapy are urgently needed. This study aimed to evaluate the predictive value of serum levels of uromodulin (sUMOD) in patients with cirrhosis and HRS treated with terlipressin and albumin (T/A). In total, 156 patients [81 patients with HRS treated with T/A, 42 patients with cirrhosis without kidney injury, and 33 patients with cirrhosis with prerenal acute kidney injury (AKI)] were included. sUMOD levels were analyzed by ELISA. Patients with HRS were prospectively followed for the composite endpoint of hemodialysis-/liver transplantation-free survival (HD/LTx-free survival). Of the 81 patients with HRS, 40 had HRS type 1 and 41 type 2. In the cohort of patients with HRS treated with T/A, median sUMOD level was 100 ng/mL (IQR 64; 144). sUMOD differed significantly between patients with HRS compared with patients without AKI (P = 0.001) but not between patients with HRS and prerenal AKI (P = 0.9). In multivariable analyses, sUMOD levels in the lowest quartile were independently associated with a lower rate of complete response to T/A (OR 0.042, P = 0.008) and a higher risk for reaching the composite endpoint of HD/LTX-free survival (HR 2.706, P = 0.013) in patients with HRS type 2 treated with T/A. In contrast, sUMOD was not significantly associated with these outcomes in patients with HRS type 1. sUMOD may be a valuable biomarker for identifying patients with HRS type 2 treated with T/A to predict response and prognosis. NEW & NOTEWORTHY: Biomarkers identifying patients with hepatorenal syndrome (HRS) and poor response to therapy are urgently needed. In this study, lower serum uromodulin (sUMOD) levels were associated with poorer response to therapy with terlipressin and albumin and consequently with poorer prognosis in patients with HRS type 2. In patients with HRS type 1, there was no association between sUMOD and poorer prognosis. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Poor sorafenib response in hepatocellular carcinoma patients is mediated by hypoxia-related 14-3-3 scaffolding proteins and induces a shift in tumor immune micromilieu

Author

Castven, Jovana, primary, Becker, Diana, additional, Heinrich, Sophia, additional, Zimpel, Carolin, additional, Castven, Darko, additional, Straub, Beate, additional, Grimminger, Peter, additional, Galle, Peter, additional, Weinmann, Arndt, additional, and Marquardt, Jens, additional

Published
2023
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7. Uromodulin serum levels are associated with poorer prognosis in patients with cirrhosis and hepatorenal syndrome

Author

Schleicher, Eva Maria, primary, Gairing, Simon J., additional, Castven, Darko, additional, Hock, Charlotte Sophie, additional, Dobbermann, Henrike, additional, Schlüter, Raffael, additional, Heinrich, Sophia, additional, Kaps, Leonard, additional, Galle, Peter, additional, Weinmann-Menke, Julia, additional, Nguyen-Tat, Marc, additional, Marquardt, Jens, additional, and Labenz, Christian, additional

Published
2023
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8. Poor response to sorafenib in HCC patients induces distinct immune-related signatures and is mediated by hypoxia-related 14-3-3 scaffolding proteins

Author

Castven, Jovana, additional, Becker, Diana, additional, Heinrich, Sophia, additional, Zimpel, Carolin, additional, Castven, Darko, additional, Straub, BeateKatharina, additional, Grimminger, Peter, additional, Galle, PeterR., additional, Weinmann, Arndt, additional, and Marquardt, JensU., additional

Published
2023
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9. Markers of cell death predict therapy response in patients with cirrhosis and hepatorenal syndrome

Author

Heinrich, Sophia, primary, Austgen, Thomas, additional, Castven, Darko, additional, Hess, Moritz, additional, Labenz, Christian, additional, Kirstein, Martha, additional, Zimpel, Carolin, additional, Stockhoff, Lena, additional, Maasoumy, Benjamin, additional, Heinrich, Bernd, additional, Wedemeyer, Hans Heinrich, additional, Galle, Peter Robert, additional, Binder, Harald, additional, Nguyen‐Tat, Marc, additional, and Marquardt, Jens Uwe, additional

Published
2022
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10. Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19

Author

Kirchner, Theresa, primary, Heinrich, Sophia, additional, Bonifacius, Agnes, additional, Engel, Bastian, additional, Ruhl, Louisa, additional, Pink, Isabell, additional, Thomas, Nele, additional, Martens, Joerg, additional, Hoeper, Marius M., additional, Blasczyk, Rainer, additional, Wedemeyer, Heiner, additional, Jaeckel, Elmar, additional, Li, Yang, additional, Falk, Christine S., additional, Eiz-Vesper, Britta, additional, and Taubert, Richard, additional

Published
2022
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12. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) specific cellular and humoral immunity in Corovavirus Disease-2019 (COVID-19) convalescence after liver transplantation-a prospective six month follow-up

Author

Kirchner, Theresa, primary, Sauer, Hagen, additional, Heinrich, Sophia, additional, Bonifacius, Agnes, additional, Louisa, Ruhl, additional, Pink, Isabell, additional, Engel, Bastian, additional, Saunders, Emily, additional, Martens, Joerg, additional, Hoeper, Marius M., additional, Blasczkyk, Rainer, additional, Wedemeyer, Heiner, additional, Jaeckel, Elmar, additional, Falk, Christine, additional, Eiz-Vesper, Britta, additional, and Taubert, Richard, additional

Published
2022
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13. OS-021-YI Molecular phenotype of chronic antibody-mediated rejection in liver transplant biopsies

Author

Engel, Bastian, Alaswad, Ahmed, Campos-Murguia, Alejandro, Zoodsma, Martijn, Höffer, Anne, Chihab, Kinan, Bosselmann, Emily, Heinrich, Sophia, Hartleben, Björn, Jonigk, Danny, Hallensleben, Michael, Murielle, Verboom, Geffers, Robert, Wedemeyer, Heiner, Xu, Chengjian, Mensah, Angelina, Kirchner, Theresa, Jaeckel, Elmar, Li, Yang, and Taubert, Richard

Published
2024
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15. Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Author

Ma, Lichun, primary, Wang, Limin, additional, Khatib, Subreen A., additional, Chang, Ching-Wen, additional, Heinrich, Sophia, additional, Dominguez, Dana A., additional, Forgues, Marshonna, additional, Candia, Julián, additional, Hernandez, Maria O., additional, Kelly, Michael, additional, Zhao, Yongmei, additional, Tran, Bao, additional, Hernandez, Jonathan M., additional, Davis, Jeremy L., additional, Kleiner, David E., additional, Wood, Bradford J., additional, Greten, Tim F., additional, and Wang, Xin Wei, additional

Published
2021
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17. The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma

Author

Heinrich, Bernd, primary, Gertz, E Michael, additional, Schäffer, Alejandro A, additional, Craig, Amanda, additional, Ruf, Benjamin, additional, Subramanyam, Varun, additional, McVey, John C, additional, Diggs, Laurence P, additional, Heinrich, Sophia, additional, Rosato, Umberto, additional, Ma, Chi, additional, Yan, Chunhua, additional, Hu, Ying, additional, Zhao, Yongmei, additional, Shen, Tsai-Wei, additional, Kapoor, Veena, additional, Telford, William, additional, Kleiner, David E, additional, Stovroff, Merril K, additional, Dhani, Harmeet S, additional, Kang, Jiman, additional, Fishbein, Thomas, additional, Wang, Xin Wei, additional, Ruppin, E, additional, Kroemer, Alexander, additional, Greten, Tim F, additional, and Korangy, Firouzeh, additional

Published
2021
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18. Markers of cell death predict therapy response in patients with cirrhosis and hepatorenal syndrome

Author

Heinrich, Sophia, Austgen, Thomas, Castven, Darko, Hess, Moritz, Labenz, Christian, Kirstein, Martha, Zimpel, Carolin, Stockhoff, Lena, Maasoumy, Benjamin, Heinrich, Bernd, Wedemeyer, Hans Heinrich, Galle, Peter Robert, Binder, Harald, Nguyen‐Tat, Marc, and Marquardt, Jens Uwe

Abstract

Hepatorenal syndrome is a major complication in patients with cirrhosis and associated with high mortality. Predictive biomarkers for therapy response are largely missing. Cytokeratin18‐based cell death markers are significantly elevated in patients with complications of chronic liver disease, but the role of these markers in patients with HRS treated with vasoconstrictors and albumin is unknown. We prospectively analyzed a total of 138 patients with HRS, liver cirrhosis without HRS and acute kidney injury treated at the University Medical Center Mainz between April 2013 and July 2018. Serum levels of M30 and M65 were analyzed by ELISA and clinical data were collected. Predictive ability was assessed by Kaplan‐Meier curves, logistic regression and c‐statistic. Primary endpoint was response to therapy. M30 and M65 were significantly increased in patients with HRS compared to non‐HRS controls (M30: p< 0.0001; M65: p< 0.0001). Both serum markers showed predictive ability for dialysis‐ and LTX‐free survival but not overall survival. Logistic regression confirmed M30 and M65 as independent prognostic factors for response to therapy. A novel predictive score comprising bilirubin and M65 showed highest predictive ability to predict therapy response. Serum levels of M30 and M65 can robustly discriminate patients into responders and non‐responders to terlipressin therapy with a good predictive ability for dialysis‐ and LTX‐free survival in cirrhotic patients. Cell death parameters might possess clinical relevance in patients with liver cirrhosis and HRS.

Published
2023
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19. CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

Author

Diggs, Laurence P., primary, Ruf, Benjamin, additional, Ma, Chi, additional, Heinrich, Bernd, additional, Cui, Linda, additional, Zhang, Qianfei, additional, McVey, John C., additional, Wabitsch, Simon, additional, Heinrich, Sophia, additional, Rosato, Umberto, additional, Lai, Walter, additional, Subramanyam, Varun, additional, Longerich, Thomas, additional, Loosen, Sven H., additional, Luedde, Tom, additional, Neumann, Ulf Peter, additional, Desar, Sabina, additional, Kleiner, David, additional, Gores, Gregory, additional, Wang, Xin Wei, additional, and Greten, Tim F., additional

Published
2021
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20. The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma.

Author

Heinrich, Bernd, Gertz, E. Michael, Schäffer, Alejandro A., Craig, Amanda, Ruf, Benjamin, Subramanyam, Varun, McVey, John C., Diggs, Laurence P., Heinrich, Sophia, Rosato, Umberto, Chi Ma, Chunhua Yan, Ying Hu, Yongmei Zhao, Tsai-Wei Shen, Tsai-Wei, Kapoor, Veena, Telford, William, Kleiner, David E., Stovroff, Merril K., and Dhani, Harmeet S.

Subjects
INNATE lymphoid cells, TUMOR microenvironment, HEPATOCELLULAR carcinoma, TUMOR-infiltrating immune cells
Published
2022
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21. High pretreatment static and dynamic alpha‐fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Author

Czauderna, Carolin, primary, Schmidtmann, Irene, additional, Koch, Sandra, additional, Pilz, Lukas, additional, Heinrich, Sophia, additional, Otto, Gerd, additional, Mittler, Jens, additional, Lang, Hauke, additional, Kloeckner, Roman, additional, Düber, Christoph, additional, Sprinzl, Martin F., additional, Worns, Marcus A., additional, Galle, Peter R., additional, Marquardt, Jens U., additional, and Weinmann, Arndt, additional

Published
2021
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26. Single-cell atlas of tumor clonal evolution in liver cancer

Author

Ma, Lichun, primary, Wang, Limin, additional, Chang, Ching-Wen, additional, Heinrich, Sophia, additional, Dominguez, Dana, additional, Forgues, Marshonna, additional, Candia, Julián, additional, Hernandez, Maria O., additional, Kelly, Michael, additional, Zhao, Yongmei, additional, Tran, Bao, additional, Hernandez, Jonathan M., additional, Davis, Jeremy L., additional, Kleiner, David E., additional, Wood, Bradford J., additional, Greten, Tim F., additional, and Wang, Xin Wei, additional

Published
2020
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28. Validation of prognostic accuracy of MESH, HKLC, and BCLC classifications in a large German cohort of hepatocellular carcinoma patients

Author

Heinrich, Sophia, primary, Sprinzl, Martin, additional, Schmidtmann, Irene, additional, Heil, Elena, additional, Koch, Sandra, additional, Czauderna, Carolin, additional, Heinrich, Bernd, additional, Philippe P Diggs, Laurence, additional, Wörns, Marcus‐Alexander, additional, Kloeckner, Roman, additional, Galle, Peter R, additional, Marquardt, Jens U, additional, and Weinmann, Arndt, additional

Published
2020
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29. High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Author

Czauderna, Carolin, Schmidtmann, Irene, Koch, Sandra, Pilz, Lukas, Heinrich, Sophia, Otto, Gerd, Mittler, Jens, Lang, Hauke, Kloeckner, Roman, Düber, Christoph, Sprinzl, Martin F, Wörns, Marcus A, Galle, Peter R, Marquardt, Jens U, and Weinmann, Arndt

Abstract

Background Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion.Objective We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort.Methods Patients with confirmed hepatocellular carcinoma (n= 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models.Results High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p< 0.01) and C stage (p< 0.001), portal vein thrombosis (p< 0.001) and extrahepatic spread (p< 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values.Conclusion Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Published
2024
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30. High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma.

Author

Czauderna C, Schmidtmann I, Koch S, Pilz L, Heinrich S, Otto G, Mittler J, Lang H, Kloeckner R, Düber C, Sprinzl MF, Wörns MA, Galle PR, Marquardt JU, and Weinmann A

Abstract

Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion., Objective: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort., Methods: Patients with confirmed hepatocellular carcinoma ( n  = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models., Results: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B ( p  < 0.01) and C stage ( p  < 0.001), portal vein thrombosis ( p  < 0.001) and extrahepatic spread ( p  < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values., Conclusion: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Published
2020
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