Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Steven M. Kawut, Susan S. Ellenberg, Michael Joseph Krowka, David Goldberg, Hugo E Vargas, David Koch, Tiffany Sharkoski, Nadine Al-Naamani, Alyson Fox, Robert Brown, Joshua Levitsky, Jae Kuen Oh, Grace D Lin, Nianfu Song, Carl Mottram, Margaret F. Doyle, David E. Kaplan, Samir Gupta, Michael B. Fallon

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, –3.8 to 7.0 mm Hg) and those allocated to placebo (–2.4 mm Hg; IQR, –4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.

Original languageEnglish (US)
JournalLiver Transplantation
DOIs
StatePublished - Jan 1 2019

Fingerprint

Hepatopulmonary Syndrome
Placebos
Vascular Endothelial Growth Factor Receptor
Complementary Therapies
sorafenib
Protein-Tyrosine Kinases
Echocardiography
Mouth
Monocytes
Theoretical Models
Quality of Life
Oxygen

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Sorafenib in Hepatopulmonary Syndrome : A Randomized, Double-Blind, Placebo-Controlled Trial. / Kawut, Steven M.; Ellenberg, Susan S.; Krowka, Michael Joseph; Goldberg, David; Vargas, Hugo E; Koch, David; Sharkoski, Tiffany; Al-Naamani, Nadine; Fox, Alyson; Brown, Robert; Levitsky, Joshua; Oh, Jae Kuen; Lin, Grace D; Song, Nianfu; Mottram, Carl; Doyle, Margaret F.; Kaplan, David E.; Gupta, Samir; Fallon, Michael B.

In: Liver Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

Kawut, SM, Ellenberg, SS, Krowka, MJ, Goldberg, D, Vargas, HE, Koch, D, Sharkoski, T, Al-Naamani, N, Fox, A, Brown, R, Levitsky, J, Oh, JK, Lin, GD, Song, N, Mottram, C, Doyle, MF, Kaplan, DE, Gupta, S & Fallon, MB 2019, 'Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial', Liver Transplantation. https://doi.org/10.1002/lt.25438
Kawut, Steven M. ; Ellenberg, Susan S. ; Krowka, Michael Joseph ; Goldberg, David ; Vargas, Hugo E ; Koch, David ; Sharkoski, Tiffany ; Al-Naamani, Nadine ; Fox, Alyson ; Brown, Robert ; Levitsky, Joshua ; Oh, Jae Kuen ; Lin, Grace D ; Song, Nianfu ; Mottram, Carl ; Doyle, Margaret F. ; Kaplan, David E. ; Gupta, Samir ; Fallon, Michael B. / Sorafenib in Hepatopulmonary Syndrome : A Randomized, Double-Blind, Placebo-Controlled Trial. In: Liver Transplantation. 2019.
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abstract = "The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, –3.8 to 7.0 mm Hg) and those allocated to placebo (–2.4 mm Hg; IQR, –4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.",
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AU - Mottram, Carl

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