Experience with inhaled iloprost and bosentan in portopulmonary hypertension

Abstract

Novel treatments, such as prostanoids or endothelin receptor antagonists, have been introduced for various forms of pulmonary arterial hypertension, but the long-term effects of these treatments on portopulmonary hypertension (PPHT) are unknown.In a retrospective analysis, the present authors assessed the safety and efficacy of inhaled iloprost, a prostacyclin analogue, and bosentan, an endothelin receptor antagonist, in patients with PPHT. In total, 31 consecutive patients with Child class A or B cirrhosis and severe PPHT were treated for up to 3 yrs with either inhaled iloprost (n513) or bosentan (n518), and the effects on exercise capacity, haemodynamics and survival were evaluated.In the iloprost group, the survival rates at 1, 2 and 3 yrs were 77, 62 and 46%, respectively. In the bosentan group, the respective survival rates were 94, 89 and 89%. Event-free survival rates, i.e. survival without transplantation, right heart failure or clinical worsening requiring the introduction of a new treatment for pulmonary hypertension, was also significantly better in the bosentan group. Bosentan had significantly better effects than inhaled iloprost on exercise capacity, as determined by the 6-min walk test, as well as on haemodynamics. Both treatments proved to be safe, especially in regards of liver function.In the present series of patients with well-preserved liver function and severe portopulmonary hypertension, treatment with both inhaled iloprost and bosentan appeared to be safe. Patients treated with bosentan had higher survival rates, but prospective controlled studies are required to confirm these findings.

Guidelines for the diagnosis and treatment of pulmonary hypertension

“…Case series suggest that epoprostenol, bosentan and sildenafil may exert beneficial haemodynamic and clinical effects in selected patients [208][209][210]. In a retrospective study treatment with bosentan appeared to be better than inhaled iloprost [211]. Careful monitoring should be performed if ERA treatment is initiated because of the hepatotoxicity of these compounds.…”

Hepatopulmonary Syndrome and Portopulmonary Hypertension in the Same Patient

“…Inhibitors of 1-endothelin as bosentan are an effective treatment in stable hepatic illness, however there is insufficient evidence of its effectiveness in patients with altered hepatic dysfunction [16]. Furthermore, patients treated with bosentan have shown better results in hemodynamic parameters and the 6 minute-walk distance test (6MWD) compared with patients treated with inhaled iloprost [17]. It has been demonstrated that treatment with ambrisentan has less hepatic toxicity and improves hemodynamic parameters with respect to bonsentan [18].…”

Treatment with a combination of bosentan and sildenafil allows for successful liver transplantation in a patient with portopulmonary hypertension

“…However, in one study, the treatment was stopped in half of the patients because of the following adverse effects: chin pain, diarrhea, erythema, arthralgia, infections, sepsis due to a catheter, thrombus, pump dysfunction, hypersplenism, impairment of liver function, and rebound pulmonary hypertension (7). Due to its excessive adverse effects and the difficulty with intravenous administration, inhaled iloprost has been the preferred treatment (6). Inhaled iloprost provides an enhancement in functional capacity; however, this improvement is not maintained in some patients.…”

“…The risk of mortality is close to 0% if the mean PAP is lower than 35 mmHg (5). However, the risk of mortality rises to 50% if the mean PAP is between 35-45 mmHg, and it increases to nearly 100% when the mean PAP is greater than 45 mmHg (3,6). If the preoperative pressure is reduced to levels below 35 mmHg, transplantation may be performed confidently.…”