Mending the Model for End‐Stage Liver Disease: An in‐depth review of the past, present, and future portopulmonary hypertension Model for End‐Stage Liver Disease exception

Abstract

Patients with portopulmonary hypertension (POPH) have an increased cardiovascular and overall mortality risk when undergoing liver transplantation (LT). However, such risk is not captured in their Model for End‐Stage Liver Disease (MELD) laboratory score. POPH MELD exception criteria were established in 2006 with the aim of prioritizing these patients for LT prior to pulmonary hypertension (PH) progression and eventual right heart failure. The original criteria emphasized a posttreatment, pre‐LT mean pulmonary arterial pressure (mPAP) of <35 mm Hg and pulmonary vascular resistance (PVR) <400 dynes‐s‐cm−5 or <5 Wood units (WU). Since 2006, there have been important advances in the treatment of POPH with pulmonary arterial hypertension (PAH)–targeted therapies and newer evidence regarding LT outcomes and risk factors for perioperative mortality. Specifically, PVR rather than mPAP has been shown to be more strongly associated with outcomes, including mortality. In addition, among treated patients with POPH, mPAP may be persistently elevated related to an elevated cardiac output or other factors that do not necessarily reflect POPH disease severity. Thus, in February 2021, the Organ Procurement and Transplantation Network approved proposed modifications to POPH MELD exception criteria, now allowing either of the following posttreatment, pre‐LT hemodynamic profiles: mPAP less than 35 mm Hg and posttreatment PVR less than 400 dynes‐s‐cm−5 (or less than 5 WU) or mPAP greater than or equal to 35 mm Hg and less than 45 mm Hg and posttreatment PVR less than 240 dynes‐s‐cm−5 (or less than 3 WU). This article reviews the history of the POPH MELD exception criteria, describes the recent modifications to the exception criteria and the evidence supporting them, and highlights unanswered questions and areas for future research.

Portopulmonary Hypertension: An Updated Review

“…72 Currently, patients with PoPH that have an adequate hemodynamic response to the medical therapy evidenced on the 3-mo follow-up heart catheterization after starting treatment can receive MELD exception points with a Median MELD at Transplant minus 3 points, according to the actual policy of the Organ Procurement Transplantation Network. 68,73 The cohort study by Savale and collaborators evaluated long-term results of OLT in a period wherein the current therapies of PH revealed a survival rate of 80%, 77%, and 77% in 6 mo, 1 y, and 3 y after OLT, respectively. In addition, 45% of patients who underwent OLT had PH resolutions.…”

The Clinical Course of Portopulmonary Hypertension and Outcomes With Endothelin Receptor Antagonist Treatment: Observational Study of Data From the US Organ Procurement and Transplantation Network

“…2 MELD exception criteria were defined in 2006 for patients with PoPH and mPAP >35 mm Hg, who achieved hemodynamic improvement (mPAP <35 mm Hg, PVR <400 dynes•s/cm 5 [<5 WU], and satisfactory RV function) following treatment with an approved PAH therapy. 2,17 These criteria were revised to allow either of the following post-PAH treatment, pre-LT hemodynamic profiles: mPAP <35 mm Hg and posttreatment PVR <400 dynes•s/cm 5 (<5 WU) or mPAP ≥35 mm Hg and <45 mm Hg and posttreatment PVR <240 dynes•s/cm 5 (<3 WU). 2 Real-world data from observational studies have provided insights into clinical management and outcomes in patients with PoPH.…”

“…2,17 These criteria were revised to allow either of the following post-PAH treatment, pre-LT hemodynamic profiles: mPAP <35 mm Hg and posttreatment PVR <400 dynes•s/cm 5 (<5 WU) or mPAP ≥35 mm Hg and <45 mm Hg and posttreatment PVR <240 dynes•s/cm 5 (<3 WU). 2 Real-world data from observational studies have provided insights into clinical management and outcomes in patients with PoPH. 12,[18][19][20] US surveys showed marked variability in screening for PoPH in LT candidates, heterogeneity in PoPH management following LT, and lack of guideline concordance when managing elevated mPAP and PVR to achieve LT eligibility.…”

Portopulmonary hypertension: May we agree to disagree?

“…Aside from the buffet of treatment options, diagnostic criteria for POPH have changed (2018 WHO and 2022 ERS), and UNOS/OPTN POPH MELD exception criteria have been modified. [6,7] Specifically, the diagnosis of PAH (and by default POPH) has changed with mean pulmonary artery pressure (mPAP) > 20 mm Hg now the cutoff criteria rather than > 25 mm Hg. Normal pulmonary vascular resistance is now thought to be <2 Wood units rather than 3 Wood units (especially in POPH due to the inherent higher cardiac outputs associated with portal hypertension).…”

“…Aside from the buffet of treatment options, diagnostic criteria for POPH have changed (2018 WHO and 2022 ERS), and UNOS/OPTN POPH MELD exception criteria have been modified 6,7. Specifically, the diagnosis of PAH (and by default POPH) has changed with mean pulmonary artery pressure (mPAP) >20 mm Hg now the cutoff criteria rather than >25 mm Hg.…”