Sotatercept for the treatment of portopulmonary hypertension: a case report

Portopulmonary Hypertension is a subtype of pulmonary arterial hypertension with high mortality. There are extremely few clinical trials to guide treatment in portopulmonary hypertension, which is typically based on the approach to treatment for other types of pulmonary arterial hypertension. Sotatercept, the newest pulmonary arterial hypertension approved therapeutic, is a novel activin signaling inhibitor which has been shown to significantly improve disease severity and enhance survival when added to background therapy in pulmonary arterial hypertension. Unfortunately, portopulmonary hypertension patients were excluded from the clinical trials that led to Sotatercept approval, and the efficacy, safety, and tolerability of Sotatercept in portopulmonary hypertension remains unclear.

Methods
Here we describe, to the best of our knowledge, a case report of the first use of Sotatercept in the treatment of portopulmonary hypertension, combined with single cell RNA sequencing and plasma proteomic analysis.

Results
We demonstrate that profiling the circulating leukocyte transcriptomic and circulating pulmonary artery proteomic signatures before and after Sotatercept treatment identifies changes in CD8 + T-Cell and Monocyte gene expression, and levels of proteins involved in inflammation and ubiquitination. Sotatercept appears well tolerated, effective in reducing pulmonary hypertension hemodynamic severity in a portopulmonary hypertension patient refractory to conventional pulmonary hypertension therapies, but may be associated with the development of hepatopulmonary syndrome.

Conclusions
This report demonstrates tolerability and efficacy of Sotatercept in portopulmonary hypertension, identifies candidate biomarkers of treatment response, but also suggests caution may be warranted. Findings from this work support further investigation of Sotatercept in the treatment of portopulmonary hypertension.