Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension

The outcome of liver transplantation (LT) in the presence of moderate to severe POPH is
significantly poor with a 50% reported mortality rate in LT recipients having a mean
pulmonary artery pressure (mPAP) >35 mmHg and 100% when the mPAP is greater than 50 mmHg;
therefore, making moderate to severe POPH a contraindication to liver transplants. Those
recipients with significant pulmonary artery pressure (PAP) may be denied the opportunity for
transplant unless the mPAP is brought below 35 mmHg with medical treatment. This study will
test the efficacy & safety of the combination of using ambrisentan and tadalfil in reducing
the Pulmonary Arterial Pressure to below 35 mmHg in patients with moderate to severe POPH as
a means to candidacy for liver transplantation.

Inclusion Criteria:

- Child-Pugh Class Class A & B Cirrhosis

- mPAP ≥35mmHg

- Pulmonary Capillary Wedge Pressure (PWCP) <15mmHg on Right Heart Catheterization's
(RHCs)

- mPAP > 50mmHg will be considered eligible unless they are World Health Organization
(WHO) Functional Class IV

Exclusion Criteria:

- End stage renal disease on hemodialysis (ESRD on HD)

- Renal dysfunction and GFR < 30

- AST, ALT > 5 times the upper limit of normal

- Total bilirubin ≥ 6.0

- INR > 2

- Initially, Child-Pugh Class C patients will be excluded; however, after the first
5 patients are included, if there is no signal of worsening liver function, the
protocol may be amended to include patients with Class C cirrhosis.