Table 1:
Studies that included ≥ 3 patients and described the effect of PAH-specific therapies in PoPH.
| First author, year, reference |
n | WH O funct ional class |
PVR (dyn*s*cm −5) |
Medication | MELD / Child-Pugh score |
Outcomes |
|---|---|---|---|---|---|---|
| Phosphodiesterase-5 inhibitors | ||||||
| Hemmes et al, 2009(87) | 10 | I- IV | Mean ±SD 664 ± 336 |
Sildenafil 20–50mg three times daily. | MELD:mean ±SD 14±3.3 | ✓Improvement in functional class, exercise tolerance and cardiopulmonary hemodynamics. Three patients were listed for liver transplantation and one was successfully transplanted. |
| Reichenberger et al, 2006(48) | 13 | III- IV | Mean ±SD 759± 338 |
Sildenafil 50mg three times daily. | C-P: A,B,C | ✓Improvement in functional class, exercise tolerance and cardiopulmonary hemodynamics. |
| Fisher et al, 2015(88) | 20 | III- IV | Mean ±SD 683± 259 |
Sildenafil 20–25 mg three times daily (n=19), tadalafil 40 mg daily (n=1) | C-P: A,B,C MELD: median,(range) 15 (13–18) |
✓Improvement in functional class and cardiopulmonary hemodynamics. No change in exercise tolerance. |
| Gough et al, 2009(89) | 11 | I -III | Mean: 575 | Sildenafil 25–50mg three times daily. | C-P: B,C MELD:mean ±SD 14±4.6 |
✓Improvement in cardiopulmonary hemodynamics. One patient had a successful liver transplant. |
| Endothelin receptor antagonists | ||||||
| Hoeper et al (2005)(41) | 11 | II-IV | Mean ±SD 944 ±519 |
Bosentan 62.5 mg twice daily for 4–8 weeks, increased to 125 mg twice daily | C-P: A | ✓Improvement in functional class, exercise tolerance and cardiopulmonary hemodynamics. One patient had worsening ascites. No evidence of liver toxicity. |
| Savale et al (2013) (52) | 34 | II-IV | Mean ±SD 696 ± 264 |
Bosentan 62.5 mg twice daily for 4 weeks, increased to 125mg twice daily | C-P: A, B | ✓Improvement in functional class, exercise tolerance and cardiopulmonary hemodynamics. Three patients died of right heart failure. Elevation of liver enzymes was noted in several patients. |
| Cartin-Ceba et al (2011)(42) | 13 | II-III | Median (IQR) 445 (329–834) |
Ambrisentan 5mg daily for 4 weeks, increased to 10mg daily | C-P: A,B,C MELD: median of 10 (IQR,8.5–15) |
✓Improvement in cardiopulmonary hemodynamics and BNP levels. One patient underwent successful liver transplantation. One patient had periorbital bleeding, peripheral edema and 8 pounds weight gain. No evidence of liver toxicity |
| Prostacyclin analogues | ||||||
| Krowka et al (1999)(90) | 15 | II-IV | Mean ±SD: Acute phase: 525±286 Long-term phase: 373±191 |
Acute phase: IV epoprostenol 4–10 ng/kg/min over 60 min (n=14). Long-term phase: IV epoprostenol up to 48 ng/kg/min (n=10) |
C-P: B,C | ✓Acute phase: improvement in cardiopulmonary hemodynamics. Hypotension, headache and nausea were noted. ✓Long-term phase: no improvement in cardiopulmonary hemodynamics. One patient died of worsening heart failure and another had sudden death after successful liver transplantation. |
| Awdish et al, 2013(91) | 21 | I-III | Mean ±SD 537± 160 |
IV epoprostenol 20.8 ± 13.9 ng/kg/min |
C-P: A,B,C MELD: mean ±SD: 12.5 ±5.1 |
✓Improvement in exercise tolerance and cardiopulmonary hemodynamics. Seven patients were transplanted successfully, and four patients were listed for liver transplantation. |
| Kuo et al, 1997(92) | 4 | II-IV | N/A | IV epoprostenol up to 28 ng/kg/min | C-P: B | ✓Improvement in cardiopulmonary hemodynamics. |
| Melgosa et al, 2010(47) | 21 | I- IV |
Acute phase: 564±282 Long-term phase: 802±313 |
Acute-phase: 21 patients were given 2.8 µg of inh iloprost. Long-term phase: inh iloprost 5 µg six times daily for 1 year (3 patients also received bosentan 125 mg twice daily) |
MELD: mean ± SD Acute-phase 15.0±2.5 Long-term phase 11.1±5.3 |
✓Acute-phase: improvement in cardiopulmonary hemodynamics. ✓Long-term phase: improvement in exercise tolerance and functional class but no change in cardiopulmonary hemodynamics. Two patients worsened their pulmonary hypertension. |
| Sakai et al, 2009 (43) | 3 | N/A | 249,304, 718 | IV treprostinil : 45, 36 and 106 ng/kg/min |
MELD: 22, 33, N/A | ✓Improvement in cardiopulmonary hemodynamics in two patients who underwent successful liver transplantation. |
| Ashfaq et al,2006(30) | 16 | II-IV | Mean ±SD: Moderate PoPH (n=6) 402±87 Severe PoPH (n=10) 551±92 |
IV epoprostenol (n=15, 2 patients also received bosentan). One patient was treated with diltiazem. | C-P: B,C MELD: mean ±SD: Moderate 11.9 ± 4.5 Severe 15.2 ± 4.6 |
✓Improvement in cardiopulmonary hemodynamics. Eleven patients were successfully transplanted. |
| Sussman et al, 2006(93) | 8 | N/A | Mean 410 | IV epoprostenol at 2–8 ng/kg/min | MELD: mean ±SD 17±6.4 | ✓Improved cardiopulmonary hemodynamics. Six patients were listed for liver transplantation (four were successfully transplanted) |
| Hoeper et al, 2007 (46) | 31 | II-III | 812±337(iloprost) and 866±422 (bosentan) | Iloprost 5ug inh six times daily (n=13) or bosentan 125mg twice daily (n=18). | C-P: A,B MELD:mean ±SD 12±3 and 10±3 |
✓Bosentan was a safe. Compared with iloprost, patients treated with bosentan had better effects on exercise capacity, hemodynamics and higher survival and event-free survival. |
| Fix et al,2007(94) | 19 | II-IV | Mean 670 (95%CI: 556–784) |
Epoprostenol (n=19). In 7 patients sildenafil was added. | C-P: A,B,C MELD: median, (range) 14 (7–26) |
✓Improved cardiopulmonary hemodynamics. Two patients underwent liver transplantation. Epoprostenol was discontinued in 2 and sildenafil in 4 patients given side effects. |
WHO: World Health Organization
N/A: not available
MELD: Model for End-stage Liver Disease
C-P: Child-Pugh score
SD: standard deviation
IQR: interquartile range
CI: confidence interval
mPAP: mean pulmonary artery pressure
PVR: pulmonary vascular resistance
IV: intravenous
Inh: inhaled