Sildenafil treatment for portopulmonary hypertension

Abstract

Portopulmonary hypertension (POPH) is regarded as a subtype of pulmonary arterial hypertension (PAH); however, established PAH therapies have not been evaluated for this condition.The current authors treated 14 patients (four male, 10 female; mean (range) age 55 (39-75) yrs) with moderate (n51) or severe (n513) POPH caused by alcoholic liver disease (n57), chronic viral hepatitis (n53), autoimmune hepatitis (n53), and hepatic manifestation of hereditary haemorrhagic teleangiectasia (n51) with oral sildenafil. Eight patients were newly started on pulmonary vasoactive treatment, while six patients were already on treatment with inhaled prostanoids (iloprost, n55; treprostinil, n51). During treatment with sildenafil, mean¡SD 6-min walk distance increased from 312¡111 m to 397¡99 m after 3 months, and 407¡97 m after 12 months. Mean¡SD pro-brain natriuretic peptide levels decreased from 582¡315 ng?mL -1 to 230¡278 ng?mL, and to 189¡274ng?mL -1 after 3 and 12 months, respectively. Two patients died after 1 and 2 months from liver failure and cardiac failure, respectively. There was a similar response to sildenafil treatment after 3 and 12 months in patients on monotherapy and those on combination therapy.In conclusion, sildenafil might be effective in monotherapy and in combination therapy with inhaled prostanoids in portopulmonary hypertension, leading to significant improvement by 3 months and sustained response over 12 months.

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

“…Anecdotal reports suggest that ERAs, PDE-5is, sGC stimulators and prostacyclin analogues may be used in this patient population [214,[350][351][352][353][354][355][356]. This includes potentially hepatotoxic drugs such as bosentan, but it should be noted that this compound tends to accumulate in patients with severely impaired liver function (i.e.…”

“…The absence of viral particles in the complex plexiform lesions found from these patients suggests that an indirect action of viral infection on inflammation and growth factors may act as a trigger in a predisposed patient. [344] It is recommended that the treatment algorithm for patients with other forms of PAH should be applied to patients with PAH associated with portal hypertension, taking into account the severity of liver disease C I [214,[350][351][352][353][354][355][356] Liver transplantation may be considered in selected patients responding well to PAH therapy C IIb [361][362][363] It is recommended that patients affected by PAH associated with portal hypertension should be referred to centres with expertise in managing both conditions C I [344] Anticoagulation is not recommended in patients with PH associated with portal hypertension C III [365] Liver transplantation is contraindicated in patients with severe and uncontrolled PAH C III [361][362][363] PAH: pulmonary arterial hypertension; PH: pulmonary hypertension. with other risk factors for PAH, such as liver disease (chronic hepatitis B or C), exposure to drugs or toxins or PE due to i.v.…”

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].…”

Experience with inhaled iloprost and bosentan in portopulmonary hypertension

“…Case reports and smaller case series suggest that treatments that are effective in other forms of PAH, i.e. prostanoids, phosphodiesterase-5 inhibitors and endothelin receptor antagonists, may also be beneficial in patients with PPHT [5][6][7]. The long-term safety and effectiveness of these treatments in PPHT, however, have never been evaluated.…”