• To estimate the probability of achieving a mPAP to less than 35 mmHg and a PVR less than 3 Wood-units in subjects with severe portopulmonary hypertension undergoing OLT treated for 24 weeks with treprostinil. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  

• To assess the effect of treprostinil therapy on safety, secondary efficacy endpoints and chemokine profiles. [ Time Frame: 24 weeks, and 30 day post-OLT and one year post-OLT ] [ Designated as safety issue: Yes ]
  

Portopulmonary hypertension (PoPH) is characterized by the presence of pulmonary arterial hypertension (PAH) in the setting of portal hypertension, and is considered the third most common cause of PAH[[1], [2]]. Approximately 2 to 6% of patients with portal hypertension demonstrate significant pulmonary hypertension based on hemodynamic observation[[3], [4], [5]]. In those patients undergoing liver transplant evaluation, the prevalence of PAH is approximately 5-6%[[4], [6], [7]]. PoPH is associated with a median survival ranging from 8 months to 2.3 years.

Among patients undergoing liver transplantation, the presence of PoPH contributes significantly to morbidity and mortality[[8], [9], [10]]. In particular, patients with PoPH who undergo OLT with mean pulmonary artery pressure (PAPm) > 35 mmHg and/or pulmonary vascular resistance (PVR) > 250 dyn/s/cm5 have > 90% risk of death posttransplant[[8]]. As such, in many transplant centers, the presence of severe PoPH ((PAPm) > 35 mmHg and/or pulmonary vascular resistance (PVR) > 250 dyn/s/cm5) is considered an absolute contraindication to OLT[[6], [11], [12]]. These patients thus have limited treatment options.

To date, pulmonary vasodilator medication use in the setting of PoPH has largely been limited to single case reports or small case series. These include intravenous (IV)/inhaled prostacyclin, sildenafil and bosentan [[15], [16], [17], [18], [19], [20], [21]]. More recently, encouraging results have been published in open label studies with the use of IV epoprostenol which was shown to improve pulmonary hemodynamics and possibly survival [[19], [21], [22]]. Specifically, in patients with severe PoPH who were referred for OLT, initiation of IV epoprostenol allowed for mPA < 35 mmHg in certain cases, allowing a successful bridge to OLT [[21], [22]].

Treprostinil is approved as a continuous subcutaneous (SC) or intravenous (IV) infusion by the FDA for the treatment of WHO group I PAH with New York Heart Association (NYHA) Class II, III or IV symptomatology[[13], [14]]. To date, treprostinil has not been studied in the setting of PoPH; however, it is commonly prescribed in this setting. This is an observational, open-label, multi-center study will attempt to document the safety and efficacy profile of this agent in PoPH to facilitate OLT efficacy profile of this agent in PoPH to facilitate OLT.