title: Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension.
abstract: Portopulmonary hypertension (PPHTN) represents a constrictive pulmonary vasculopathy in patients with portal hypertension. Liver transplantation (LT) may be curative and is usually restricted to patients with mild-to-moderate disease severity characterized by a mean pulmonary artery pressure (mPAP < 35 mm Hg). Patients with severe disease (mPAP > 50 mm Hg) are usually excluded from transplantation. We describe a patient with severe PPHTN, initiated on sequential and ultimately combination therapy of prostacyclin, sildenafil, and bosentan (PSB) pretransplantation and continued for 2 years posttransplantation. Peak mPAP on PSB therapy was dramatically reduced from 70 mm Hg to 32 mm Hg pretransplantation, and continued therapy facilitated a further fall in mPAP to 28 mm Hg posttransplantation. The pulmonary vascular resistance index fell from 604 to 291 dyne second(-1) cm(-5). The perioperative mPAP rose to 100 mm Hg following an episode of sepsis and fell with optimization of PSB therapy. In conclusion, this is the first reported patient with severe PPHTN using this combination of vasodilator therapy as a bridge to LT and then as maintenance in the posttransplantation phase. This regimen may enable LT in similar patients in the future, without long-term consequences.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, England.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Austin
authors.forename: Neil I
authors.initials: NI
authors.lastname: McDougall
authors.forename: Julia A
authors.initials: JA
authors.lastname: Wendon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sizer
authors.forename: Alex S
authors.initials: AS
authors.lastname: Knisely
authors.forename: Mohammed
authors.initials: M
authors.lastname: Rela
authors.forename: Carol
authors.initials: C
authors.lastname: Wilson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Callender
authors.forename: John G
authors.initials: JG
authors.lastname: O'Grady
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heneghan
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000077300:Bosentan; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000009:adverse effects / Q000627:therapeutic use*; D008107:Liver Diseases / Q000503:physiopathology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D016285:Iloprost; D000077300:Bosentan