Portopulmonary Hypertension: Treatment
We reported the longest follow-up study for patients undergoing liver transplantation with POPH in 2014.41 Seven patients with moderate to severe POPH received a liver transplant at our institution between June 2004 and January 2011. Mean pulmonary artery pressure was reduced to < 35 mm Hg, with appropriate POPH therapy in all of the patients. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. The 1 patient who did not survive died from complications related to recurrent hepatitis C and cirrhosis, not from POPH-related issues. Four of the remaining 6 patients continue to require oral vasodilator therapy post-transplant, suggesting irreversible remodeling of the pulmonary vasculature. Two patients (4.4 and 8.5 years post-transplant) have no evidence of pulmonary hypertension post-transplant and therefore do not require medical treatment for pulmonary hypertension. We concluded that POPH responsive to vasodilator therapy is an appropriate indication for liver transplant, with excellent long-term survival.
Hollatz et al published their data on 11 patients with moderate to severe POPH who were successfully treated (mostly with oral sildenafil and subcutaneous treprostinil) as a bridge to liver transplant.42 The mortality rate was 0, with a follow-up duration of 7 to 60 months. Interestingly, 7 of the 11 patients (64%) were off all pulmonary vasodilators post-transplant. Ashfaq et al reported similar results.11 Nine of 11 patients with treated moderate to severe POPH who received liver transplants stopped vasodilator therapy at a median period of 9.2 months post-transplant. Raevens et al described a group of 3 patients with POPH who went on to liver transplant after their pulmonary pressures were decreased with combined oral vasodilator therapy: 1 required continued long-term vasodilator therapy, another was weaned off medications after transplant, and the third patient died during the liver transplant from perioperative complications that induced uncontrolled pulmonary hypertension.43
Patient Selection
In 2006, the United Network for Organ Sharing (UNOS) initiated a policy whereby a higher priority for liver transplantation was granted for highly selected patients in the United States.44 UNOS policy 3.6.4.5.6 upgraded POPH patients to a MELD score of 22, with an increase in MELD every 3 months as long as MPAP remained < 35 mm Hg and PVR remained < 400 dynes/s/cm–5. One hundred fifty-five patients were granted MELD exception points for POPH between 2002 and 2010 and went on to receive liver transplants.45 Goldberg et al collected data from the Organ Procurement and Transplantation Network (OPTN) and compared outcomes of patients with approved POPH MELD exception points versus waitlist candidates with no exception points.46 One hundred fifty-five waitlisted patients received POPH MELD exception points, with only 43.1% meeting OPTN exception requirements. One-third did not fulfill hemodynamic criteria consistent with POPH or had missing data, and 80% went on to receive a liver transplant. Waitlist candidates receiving POPH MELD exception points also had increased waitlist mortality and several early post-transplant deaths. The authors felt these data highlighted the need for OPTN/UNOS to revise their policy for POPH MELD exceptions points, revise how points are rewarded, and continue research to help risk stratify these patients to minimize perioperative complications.
Conclusion
Several effective medical treatment regimens are available, including prostanoids, endothelin receptor antagonists, and PDE-5 inhibitors. Liver transplantation is a potential cure but is only recommended if MPAP can be decreased to ≤ 35 mmHg. Long-term follow-up studies have shown these patients do well several years post-transplant but may continue to require oral therapy for their POPH.
