How should we treat portopulmonary hypertension?

T he development of pulmonary arterial hypertension in the setting of advanced liver disease (portopulmonary hypertension (POPH)) has certainly captured the attention of all liver transplant centres, but why? For patients with moderate-to-severe POPH (mean pulmonary artery pressure (mPAP) .35 mmHg and pulmonary vascular resistance (PVR) .400 dyne?s?cm-5), the risk of intra-operative death and post-transplant hospitalisation mortality in otherwise acceptable liver transplant candidates is high [1]. The American Association for the Study of Liver Disease Practice Guidelines have espoused Doppler echocardiography screening for all liver transplant candidates [2]. However, once POPH is confirmed by right-heart catheterisation, what therapeutic approach should be considered? More generally, what should the approach be to treating POPH, irrespective of liver transplant candidacy? POPH is not simply a liver transplant issue, but that area of clinical medicine has raised awareness of this entity over the past few years. Recent evidence from France underscores the importance of POPH: it was the third-most common type of pulmonary hypertension seen in a consortium of 17 French hospitals [3]. The French evidence mirrors that of the Mayo Clinic (Rochester, MN, USA) over the past 10 yrs. POPH is the third-most common disorder documented in the Mayo Pulmonary Hypertension Clinic since 1996. In the current issue of the European Respiratory Journal, REICHENBERGER et al. [4] describe the results of an uncontrolled study of 12 unstable POPH patients who received sildenafil (f50 mg three times daily) as either initial monotherapy (n56) or as an addition to existing prostacyclin therapy (n56). These patients had moderate-to-severe POPH as defined by mPAP and PVR. An additional 20 POPH patients who were stable or had mild POPH were excluded from the study (including three patients who were being treated with bosentan), so some degree of selection bias did exist. Sildenafil appeared to provide therapeutic benefit (decreasing mPAP and PVR) when evaluated at 3 months, but the haemodynamic benefit was not sustained at 12 months in seven patients, as measured by PVR, mPAP and cardiac index. Curiously, the 6-min walk distance did continue to improve at both 3 months and 12 months. This further illustrates the importance of longer-term follow-up in pulmonary hypertension trials than the usual 12-to 16-week end-points. Compared with baseline, the small group who received combination therapy seemed to have the best benefit in terms of PVR at 12 months. Obviously, these trends are based on only a few patients (and subjective interpretation of …