Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol.

Moderate to severe portopulmonary hypertension (PPHTN) increases the risks of orthotopic liver transplantation (OLT). Epoprostenol is an effective treatment of PPHTN, but long-term effects on pulmonary hemodynamics or liver function in PPHTN are poorly defined. We sought to describe the long-term effects of treatment with or without epoprostenol on pulmonary hemodynamics, liver biochemistries, and survival in patients with moderate to severe PPHTN at a single center. A large retrospective cohort was identified with moderate to severe PPHTN diagnosed before OLT. Baseline and follow-up pulmonary hemodynamics and liver biochemistries were compared and outcomes assessed. Nineteen patients were treated with epoprostenol and 17 were not treated with epoprostenol. There were significant improvements in mean pulmonary artery pressure (MPAP, 48.4-36.1 mm Hg; P < 0.0001), pulmonary vascular resistance (PVR, 632-282 dynes . s . cm(-5); P < 0.0001), and cardiac output (5.7 to 7.7 L/min; P = 0.0009) with epoprostenol after a median of 15.4 months. Liver biochemistries did not change significantly, and survival did not seem to differ between the 2 groups (hazard ratio, 0.85; P = 0.77). In the epoprostenol group, patients who survived had greater absolute changes in MPAP, transpulmonary gradient, and PVR than those who died. Two patients in the epoprostenol group successfully underwent OLT. Long-term epoprostenol therapy greatly improves pulmonary hemodynamics in patients with PPHTN. Liver biochemistries are not greatly changed. Survival seemed not to differ between treatment groups. A minority of patients treated with epoprostenol will improve sufficiently to undergo OLT.     

Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary hypertension

BACKGROUND: Portopulmonary hypertension is a known complication in the liver transplant candidate. Intravenous epoprostenol has been demonstrated to decrease pulmonary artery pressures and possibly remodel right ventricle geometry. METHODS: In this report, we document the efficacy of inhaled aerosolized epoprostenol in a patient with portopulmonary hypertension. The effect was of rapid onset and offset. RESULTS: After 10 min of delivery, mean pulmonary artery pressure decreased 26%; cardiac output increased by 22%; pulmonary vascular resistance decreased by 42%; and the transpulmonary gradient decreased by 29%. There were no untoward side effects. CONCLUSION: The inhaled route of delivery of epoprostenol is potential alternative for the acute therapy of portpulmonary hypertension.     

Assessment of acute pulmonary vascular reactivity in portopulmonary hypertension.

The role of acute pulmonary vasodilator testing in portopulmonary hypertension (PoPH), a current contraindication for orthotopic liver transplantation (OLT), has not been thoroughly elucidated. The purpose of this work was to analyze the results of acute vasodilator testing with inhaled nitric oxide (NO), to compare them with intravenous epoprostenol (PGI(2)), and to investigate the acute effects of the oral vasodilator isosorbide-5-mononitrate (Is-5-MN), in patients with PoPH. A total of 19 patients with PoPH (male/female = 9/10) were studied. Pulmonary hemodynamic measurements were performed at baseline and during NO inhalation (40 ppm); additionally, 15 patients were tested with PGI(2) (2-12 mug/kg/minute) and 8 were tested with Is-5-MN (20-40 mg). Inhaled NO reduced pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) by 5.7% and 11.0%, respectively. PGI(2) elicited greater reductions in PAP (11.8%) and PVR (-24.0%), and produced a 28% drop in systemic vascular resistance (SVR) and a 17% increase in the cardiac index (CI). Is-5-MN reduced PAP by 25.6% and PVR by 21.5%, without systemic changes. There was good agreement between the response to PGI(2) and Is-5-MN: 6 patients of the whole series (32%) decreased PAP >20% from baseline, reaching a final value < or = 35 mmHg, the current limit for OLT. In conclusion, acute vasodilator testing has a relevant role in PoPH, as it identifies one-third of patients able to reach a more favorable hemodynamic situation, which can be determinant for their management. For vasodilator testing, PGI(2) is more suitable than NO in PoPH. Is-5-MN exerts a selective effect on pulmonary circulation in patients who had already responded to PGI(2).     

Hemodynamics and survival of patients with portopulmonary hypertension.

It is not known whether patients with pulmonary arterial hypertension associated with portal hypertension (portopulmonary hypertension (PPHTN) have different disease characteristics from those of patients with other forms of pulmonary arterial hypertension. We performed a retrospective cohort study of patients with PPHTN and patients with pulmonary arterial hypertension that was idiopathic, familial, or associated with anorexigen use (IPAH) to determine whether hemodynamics or survival were different between these groups. We included consecutive patients who underwent initial pulmonary artery catheterization and vasodilator testing at our center between January 1997 and May 2001 and who were followed until January 2004. Patients with PPHTN (N = 13) had a higher cardiac index and lower pulmonary vascular resistance than patients with IPAH (N = 33) (P < or = 0.001). Right atrial pressure and pulmonary artery pressure were similar between the groups. Patients with PPHTN had a higher risk of death in multivariate analysis (hazard ratio: [HR] = 2.8, 95% CI 1.04-7.4; P = 0.04). These findings were not affected by adjustment for differences in laboratory values, hemodynamics, or therapy. In conclusion, patients with PPHTN have a higher risk of death than that of patients with IPAH, despite having a higher cardiac index and lower pulmonary vascular resistance. Future studies of the specific mechanisms of and therapy for pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.     

Progressive splenomegaly following splenic artery embolization

Nonoperative management of splenic injury is standard in hemodynamically stable patients. Splenic artery embolization is a useful adjunct to nonoperative management for patients with ongoing hemorrhage. However, the complications of embolization are not well defined. We report a case of progressive splenomegaly requiring delayed splenectomy after embolization. A 57-year-old hemodynamically stable, blunt trauma patient had a Grade III splenic injury with associated subcapsular hematoma. Nonoperative management was initiated, but his hemoglobin levels progressively declined prompting proximal splenic artery embolization. His hemoglobin levels remained stable postembolization and he was discharged on postinjury day 5. The patient was readmitted 10 days later with increasing abdominal pain and shortness of breath. Repeat CT revealed an enlarged subcapsular fluid collection, but his hemoglobin level remained stable and he was discharged 5 days later. He returned again 2 days later with similar complaints, and CT demonstrated that his subcapsular fluid collection was further enlarged. Repeat hemoglobin level was again stable. The patient requested operative intervention due to intractable pain, and splenectomy was performed without complications. Operative findings included a sterile, contained subcapsular hematoma. Splenic embolization has emerged as an adjunct to nonoperative management of splenic injury; however, the indications for splenic embolization are yet to be defined, and the spectrum and frequency of potential complications are poorly documented. This case report highlights a potentially serious complication that can occur after splenic embolization.     

Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation.

Liver transplantation (LT) may be indicated in cirrhotic patients with underlying pulmonary artery hypertension. However, severe pulmonary artery hypertension with mean pulmonary artery pressure (mPAP) above 50 mmHg has even been considered a contraindication to LT. We present a cirrhotic patient with an mPAP of 56 mmHg measured using right heart catheterization (RHC) and with severely compromised physical capacity. She was first treated with sildenafil (Viagra), a potent novel vasodilator, and successfully transplanted later. The mPAP decreased with sildenafil to the level of 28-31 mmHg and her general condition improved markedly. An LT using piggyback technique was performed 16 weeks later. Despite 2 reoperations for bleeding, the outcome has been excellent. In conclusion, treatment of severe portopulmonary hypertension (PHT) with sildenafil is effective. If a decrease in mPAP is achieved with sildenafil, it may improve the result of LT, even though no evidence of reversibility of PPHTN exists.     

Novel use of sildenafil in the treatment of portopulmonary hypertension.

Portopulmonary hypertension is a poorly understood and uncommon complication of advanced chronic liver disease. Current therapy is based largely on treatment options proven in idiopathic pulmonary hypertension. The severity of the portopulmonary hypertension should best be attenuated medically before attempting combined liver and lung transplantation to avoid increased peri-operative mortality. This case report describes the successful use of sildenafil to decrease the pulmonary vascular resistance in a patient with hepatitis-C cirrhosis who was preparing for liver transplantation.     

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension.

Pulmonary artery hypertension in association with liver failure (portopulmonary hypertension [PPHTN]) is a significant barrier to liver transplantation because patients with this condition have a very high mortality when transplantation is undertaken. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, reduces pulmonary artery pressure (PAP) in some patients with primary pulmonary hypertension, but its effect in patients with PPHTN is controversial. We investigated the hemodynamic effects of inhaled NO in 6 patients with PPHTN. Five of 6 patients responded to NO inhalation with decreases in PAP and pulmonary vascular resistance of greater than 10%; these decreases were statistically significant at NO concentrations of 10 and 30 ppm. Cardiac output did not significantly change. We conclude that inhalation of NO reduces PAPs in some patients with PPHTN.     

血管活性物质在门肺高压症发病机制中的作用

目的 研究内皮素-1(ET-1)、一氧化氮(NO)、血栓素A2(TXA2)、前列环素(PGI2)、5 羟色胺(5-HT)和转移生长因子-β1(TGF-β1)在门肺高压症(PPHTN)发病机制中的作用.方法 对4 例PPHTN(P 组)和12 例PHT患者(C 组)进行病例-对照研究,另设10 例胃肠道肿瘤患者作为正常对...     

Orthotopic liver transplantation in a patient with severe portopulmonary hypertension

Liver transplantation in patients with severe portopulmonary hypertension (PPH) has been associated with mortality rates in the range of 70% to 80%. Preoperative long-term epoprostenol therapy reverses pulmonary hypertension and may be a valuable possibility to reduce mortality in patients with severe PPH undergoing orthotopic liver transplantation. We want to report a patient with severe PPH, who was treated with intravenous epoprostenol for an 8-month period, after which pulmonary vascular resistance had decreased from 12 to 3 Wood units. Nevertheless, the patient developed intractable perioperative right heart failure necessitating transient mechanical circulatory support. The patient was weaned from mechanical circulatory support, but died from another episode of acute right heart failure after 28 days. Complicated liver transplantation associated with major cardiovascular stress is obviously not tolerated in patients with severe portopulmonary hypertension even after preoperative long-term epoprostenol therapy.     

Reversal of pulmonary hypertension and subsequent repair of atrial septal defect after treatment with continuous intravenous epoprostenol.

We report the first case in the world literature of a patient with an atrial septal defect, severe pulmonary hypertension, and equalization of pulmonary and systemic pressures, who underwent successful closure of an ASD following prolonged therapy with the intravenous vasodilator epoprostenol. Judicious use of continuous prostacyclin in apparently inoperable patients with congenital heart disease may be associated with significant reversal of pulmonary hypertension, and conversion to an operable state.     

Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates

Portopulmonary hypertension (PPHTN) is a recognized complication of end-stage liver disease that adversely affects the outcome of orthotopic liver transplantation (OLT). There are limited data on the role of Doppler echocardiography in assessing pulmonary artery systolic pressure (PASP) in this population. The purpose of our study was to examine the accuracy of Doppler echocardiography in evaluating pulmonary artery pressures in liver transplant candidates. Clinical and demographic data were gathered retrospectively for 78 liver transplant candidates (48 men and 30 women, mean age 51 ± 9.6 yr) who had PASP determined both by right heart catheterization (RHC) and echocardiography. Paired sample t-test was used to compare mean PASP by echocardiography and RHC. Correlation of PASP between echocardiography and RHC was determined using Pearson's linear correlation. Positive and negative predictive values for echocardiography for PASP > 50 mmHg are reported as compared with RHC. The mean PASP by echocardiography (43.2 ± 12.3 mm Hg) was significantly higher than mean PASP by RHC (33.7 ± 15.5 mm Hg; P < .001). Regarding PASP, there was a significant but weak correlation between echocardiography and RHC (r = 0.46, P = .01). The positive and negative predictive values of echocardiography for identifying clinically significant pulmonary hypertension (PASP > 50 mm Hg) were 37.5% and 91.9%, respectively. Echocardiography is a useful tool in estimating PASP in liver transplant candidates. Patients with apparently elevated PASP by echocardiography should undergo invasive assessment by RHC before being excluded from liver transplant. (Liver Transpl 2002;8:1051-1054.)     

Liver transplantation in high-risk patients: hepatopulmonary syndrome and portopulmonary hypertension

Two pulmonary vascular disorders, considered mutually exclusive, may be present in candidates for orthotopic liver transplantation (OLT). On the one hand, hepatopulmonary syndrome (HPS), with a prevalence about 20% in end-stage liver disease, is characterized by pulmonary vascular dilatation and abnormal gas exchange. On the other hand, portopulmonary hypertension (POPH), a process defined by pulmonary hypertension associated with portal hypertension, is less common than HPS (4%). These entities have very distinct clinical implications; whereas HPS is clinically characterized by respiratory symptoms that evolve to severe hypoxemia, patients with POPH are commonly asymptomatic, frequently diagnosed in the setting of OLT, and the symptoms appear when there is hemodynamic compromise. The pathogenesis of both entities is a putative mechanism, the imbalance of vasoactive substances in pulmonary vessels. The role of OLT to reverse these vascular disorders is controversial, although complete resolution of HPS and, less frequently, POPH following OLT has been reported. The recognition that the presence of both HPS and POPH is an important cause of morbidity and mortality among recipients of OLT has resulted in a change in the policy to select OLT candidates. Accurate identification of patients with pulmonary vascular disorders associated with liver disease should be the first step in the management of OLT candidates. Because the determinants of the prognosis of OLT in the setting of these pulmonary vascular changes have not been well established, an accurate cardiopulmonary evaluation with careful assessment of pulmonary gas exchange (in HPS) and right ventricular function (in POPH) of potential OLT recipients is mandatory before the procedure.     

全脾切除术治疗门静脉高压性脾功能亢进症

全脾切除术治疗门静脉高压性脾功能亢进(hypersplenism,简称脾亢),长期以来一直是外科治疗的首选。近年来,由于对脾脏功能的深入研究和重新认识,选择这种治疗方式是否得2例死亡。这一发现后来被命名为全脾切除术后凶险性感染(OPSI),使人们对脾功能的认识有了根本的改变。从此,被冷落的脾部分切除术、外伤性脾缝合修补术重新得到关注,脾动脉部分栓塞术、自体脾组织移植术、脾消融术等各种保脾手术应运而生,同时引发了门静脉高压性病理脾切与保的争论。由此可以看出,全脾切除术治疗门静脉高压性病理脾,既是一个老问题,也是一个新问题。主张…