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.)     

Combined liver and (heart-)lung transplantation in liver transplant candidates with refractory portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension (PPHT) has a prevalence of 5-10% in liver transplantation (LiTx) candidates. Mild PPHT is reversible with LiTx, but more severe PPHT is a contraindication to LiTx given the high intraoperative mortality due to heart failure. Prostacyclin can reduce PPHT to a level at which LiTx can be performed. In patients refractory to that treatment, combined (heart-)lung-LiTx is the only life-saving option. METHODS: We report two cases of (heart-)lung-LiTx in patients with refractory severe PPHT. RESULTS: Patient 1, a 52-year-old female with viral cirrhosis and severe refractory PPHT, received a double-lung Tx followed by LiTx. After liver reperfusion, fatal heart failure occurred. Patient 2, a 42-year-old male with viral hepatitis and congenital liver fibrosis, also suffered from severe refractory PPHT. He successfully received an en bloc heart-lung Tx followed by LiTx. The rationale to replace the heart was an anticipated risk of intraoperative right heart failure after liver reperfusion and the technical ease of heart-lung versus double-lung Tx. CONCLUSION: Severe refractory PPHT is a fatal condition seen as a contraindication to LiTx. This condition can be treated by replacing thoracal organs in addition to the liver. Additional evidence via development of a registry is required to further support application of liver-(heart-)lung Tx in patients with severe refractory PPHT.     

多普勒超声心动图筛查门肺高压症的临床研究

目的:调查门肺高压症在国内的发病情况,评估二维多普勒超声心动图作为筛查方法的临床效果。方法:于77例接受手术治疗的肝硬化门静脉高压症病人,行术前二维多普勒超声心动图检查,测算肺动脉收缩压和肺加速时间以筛查门肺高压症病人;并和标准诊断法右心导管法结果进行比较。结果:本研究样本人群中的门肺高压症发病率为3.9%,二维多普勒超声心动图筛查试验的灵敏度为100%,特异度为87.8%,真实度88.3%,阳性预测值为25%,阴性预测值为100%。结论:国内的门肺高压症发病情况与国际上报道的相似。二维多普勒超声心动图筛查法的灵敏度和阴性预测值高;阴性结果有助于排除门肺高压症,而阳性结果必须经右心导管法确诊。     

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.     

Noninvasive estimation of pulmonary vascular resistance improves portopulmonary hypertension screening in liver transplant candidates

Despite limitations in sensitivity and specificity, estimation of the pulmonary artery systolic pressure (ePASP) on echocardiography is used for portopulmonary hypertension (PoPH) screening in liver transplant (LT) candidates. We proposed that alternative echocardiographic models, such as estimated pulmonary vascular resistance (ePVR), may provide improved testing characteristics in PoPH screening. In a retrospective analysis of 100 LT candidates, we found that the formula ePVR = ePASP/VTI_RVOT + 3 if MSN (VTI_RVOT = right ventricular outflow tract time velocity integral; MSN = mid‐systolic notching of the VTI_RVOT Doppler signal) significantly improves accuracy of PoPH screening compared to ePASP. We determined the optimal ePVR cutoff for PoPH screening to be 2.76 Wood units, as this cutoff provided 100% sensitivity and 73% specificity in screening for clinically significant PoPH. Comparatively, ePASP at a cutoff of 40 mm Hg provided 91% sensitivity and 48% specificity. We devised a new screening algorithm based on the use of ePVR at intermediate ePASP values (35‐54 mm Hg), and we confirmed the testing characteristics of this algorithm in a separate validation cohort of 50 LT candidates. In screening LT candidates for PoPH, the ePASP lacks accuracy, leading to unnecessary RHCs and undiagnosed cases of PoPH. A screening algorithm which incorporates the ePVR may be more reliable.     

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.     

Neuropsychological assessment in kidney and liver transplantation candidates

INTRODUCTION: Chronic renal and liver diseases are associated with cognitive and intellectual impairment, which can be irreversible even after kidney or liver transplantation. OBJECTIVE: We sought to investigate the presence of cognitive deficits in organ transplantation candidates. METHODS: From May 2005 to March 2006, 35 organ transplantation candidates, of mean age 46.71 (+/- 13.01) years, 54.3% including females and 7.29 (+/- 4.22) years mean formal schooling. Of those, 27 (77%) were renal and 8 (23%), liver transplantation candidates. All subjects underwent a neuropsychological assessment battery designed to evaluate attention performance, executive functions, memory, language, visuaospatial, and intellectual skills. RESULTS: We found impairments in attention performance (attention span [34.3%], sustained attention [76.5%], and divided attention [77.8%]), executive functions (category formation [58.3%], errors [61.5%], and perseverative errors [30.4%]), memory (working memory [57.1%], verbal [37.1%] and visual short-term memory [31.4%], verbal [25.7%] and visual long-term memory [51.4], verbal learning [42.9%], interference susceptibility [42.9%], and verbal recognition memory [20.6%]), language (comprehension [38.1%], and vocabulary [30.8%]), visuaospatial (45.8%), and intellectual skills (50.0%). CONCLUSION: Neuropsychological (cognitive) deficits in transplant candidates are frequent, regardless of the kind of transplantation. The deficits involve several cognitive skills, such as attentional processes, executive functions, memory, language, visuaospatial, and intellectual skills. Therefore, we concluded that a pretransplant neuropsychological assessment is an important measure to detect impairments and to help understand how these difficulties can interfere with patient self-care before and after transplantation.     

Perioperative management of living-donor liver transplantation in two patients with severe portopulmonary hypertension

Liver transplantation for patients with severe portopulmonary hypertension (PPHTN) has been associated with high mortality. We conducted perioperative management of two patients with severe PPHTN for living-donor liver transplantation. The first case was a 17-year-old male with biliary atresia. He developed dyspnea at the age of 14, for which he was treated with intravenous epoprostenol for 8 months. As a result, the mean pulmonary artery pressure (MPAP) was reduced from 61 to 40 mmHg. Intraoperatively, he was treated with intravenous epoprostenol and nitric oxide (NO) inhalation. His intraoperative course was uneventful but he died from right heart failure on postoperative day (POD) 11. The second case was a 6-year-old girl with biliary atresia. When she was 5 years old, examination for a persistent cough revealed MPAP of 49 mmHg. Neither intravenous epoprostenol nor NO inhalation was effective, and she twice showed transient pulmonary hypertension during the operation. She was extubated 14 hours after the surgery, transferred out of ICU on POD 3 and discharged from the hospital on POD 99. When we compare the two cases, the factors responsible for the success of the management of the second case appear to be early extubation and the short duration of PPHTN.     

肝硬化性门肺高压患者肝移植术中体、肺循环血液动力学的变化

目的分析肝硬化性门肺高压患者肝移植术中体、肺循环血液动力学的变化。方法8例肝硬化性门肺高压患者[平均肺动脉压（MPAP）大于25mmHg]为门肺高压组,年龄50．63岁,体重45—80kg,8例肝硬化未合并门肺高压患者为对照组,年龄32．65岁,体重52—78kg。两组心功能Ⅰ或Ⅱ级,ASAⅡ-Ⅳ级,均接受改良背驮式肝移植术,观察术中体、肺循环血液动力学的变化。结果与对照组比较。门肺高压组术前MPAP、肺循环阻力指数（PVm）升高（P〈0．05）。与术前相比,无肝期两组心脏指数（CI）、MPAP、肺动脉楔压（PAWP）和中心静脉压（CVP）降低,体循环阻力指数（SVRI）升高;新肝期MPAP、CI、CVP升高。门肺高压组新肝期PVRI变化幅度高于对照组（P〈0．05）。结论肝硬化性门肺高压患者新肝期肺动脉压力和肺血管阻力增加更明显。     

Living related liver transplantation for biliary atresia with portopulmonary hypertension: case report

Portopulmonary hypertension is a complication of end-stage liver disease that adversely affects the outcome of liver transplantation (LT). We report a case of living related LT who developed severe pulmonary hypertension during and after LT. This 16-year-old girl suffered from biliary atresia, having undergone a portoenterostomy at 60 days of age, at the time of discovery of liver cirrhosis. She had been admitted to a local hospital several times for episodes of esophageal variceal bleeding. Neither dyspnea nor cyanosis was discerned until LT. Although pulmonary hypertension (PH) was disclosed by echocardiogram upon preoperative evaluation, we did not consider this a contraindication for LT, because the PH was mild. She underwent living LT from her father (graft volume/recipient body weight ratio: 0.99%). After induction of anesthesia for LT, a pulmonary flotation catheterization showed severe PH (>40 mm Hg). The pulmonary artery pressure continued to be elevated during surgery, although it was possible that her severe scoliosis affected the data. Hyperbilirubinemia was observed after LT, despite good liver function tests. On postoperative day 12, a portal vein thrombosis was detected requiring emergency thrombectomy and splenectomy. Her general condition worsened after the second surgery. She died due to cardiopulmonary failure. Autopsy showed marked hypertrophy of the right ventricle with intimal thickening in the pulmonary artery. In this case, the underestimated PH might have resulted in the unfortunate outcome. Before LT, PH should be carefully evaluated by measures including invasive assessment.     

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...     

Longitudinal assessment of mortality risk among candidates for liver transplantation

Liver allocation policy recently was modified to use the Model for End-Stage Liver Disease (MELD) for patients with chronic liver disease to stratify potential recipients according to risk for waitlist death. In this study, a retrospective cohort of 760 adult patients with chronic liver disease placed on the liver transplant waitlist between January 1995 and March 2001 and followed up for up to 74 months was studied to assess the ability of the MELD to predict mortality among waitlisted candidates and evaluate the prognostic importance of changes in MELD score over time. Serial MELD scores predicted waitlist mortality significantly better than baseline MELD scores or medical urgency status. Each unit of the 40-point MELD score was associated with a 22% increased risk for waitlist death (P < .001), whereas medical urgency status was not a significant independent predictor. For any given MELD score, the magnitude and direction of change in MELD score during the previous 30 days (ΔMELD) was a significant independent mortality predictor. Patients with MELD score increases greater than 5 points over 30 days had a threefold greater waitlist mortality risk than those for whom MELD scores increased more gradually (P < .0001). We conclude that mortality risk on the liver transplant waitlist is predicted more accurately by serial MELD score determinations than by medical urgency status or single MELD measurements. ΔMELD score over time reflects progression of liver disease and conveys important additional prognostic information that should be considered in the further evolution of national liver allocation policy. (Liver Transpl 2003;9:12-18.)     

Successful adult-to-adult living donor liver transplantation in a patient with moderate to severe portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) is one of the most devastating consequences of end-stage liver cirrhosis. When a patient has moderate to severe PPHTN, his or her candidature for liver transplantation is denied. Here we report a successful adult-to-adult living donor liver transplantation (LDLT) in a patient with moderate to severe PPHTN. The patient was a 58-yr-old female who was diagnosed with end-stage liver cirrhosis due to chronic hepatitis C. Preoperative evaluation revealed that the patient had moderate to severe PPHTN. Her mean pulmonary artery pressure (mPAP) was 35-47 mmHg without treatment. Continuous epoprostenol therapy was introduced to lower the mPAP. She underwent LDLT using an extended right hepatic lobe graft which was donated by her daughter. Prolonged artificial ventilation was necessary until postoperative day (POD) 25, after which her general condition gradually improved. By POD 72, she was in good condition and was allowed to leave the hospital. Currently, 1 yr after the operation, she visits the outpatient clinic regularly and enjoys a normal life. It should be noted, however, that the PPHTN markedly improved but did not completely resolve, as assessed by right heart catheterization 1 yr after successful LDLT.     

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.     

Treatment with sildenafil and treprostinil allows successful liver transplantation of patients with moderate to severe portopulmonary hypertension

Portopulmonary hypertension (PoPH) refers to pulmonary arterial hypertension associated with portal hypertension with or without evidence of an underlying liver disease. Despite the potential for curing PoPH with liver transplantation, the presence of moderate or severe PoPH is associated with increased morbidity and mortality and is, therefore, a contraindication to transplantation. Previous studies have predominantly used intravenous epoprostenol for treatment in order to qualify patients for liver transplantation. In this retrospective case series, we describe the clinical course of 11 patients whom we successfully treated (predominantly with oral sildenafil and subcutaneous treprostinil) in order to qualify them for liver transplantation. The mean pulmonary artery pressure significantly improved from 44 to 32.9 mm Hg, and the pulmonary vascular resistance decreased from 431 to 173 dyn second cm(-5) . There were significant improvements in the cardiac output and the transpulmonary gradient with these therapies as well. All 11 patients subsequently received liver transplants with a 0% mortality rate to date; the duration of follow-up ranged from 7 to 60 months. After transplantation, 7 of the 11 patients (64%) were off all pulmonary vasodilators, and only 2 patients required transiently increased doses of prostacyclins. In conclusion, an aggressive approach to the treatment of PoPH with sildenafil and/or treprostinil and subsequent liver transplantation may be curative for PoPH in some patients.     

Selection of live-related liver transplantation candidates

Purpose

Living donor liver transplantation (LR) is an important alternative for children. We compared our outcomes of LR and cadaveric (CAD) graft recipients, with attention to the pediatric end-stage liver disease (PELD) score and perioperative morbidity and mortality to identify appropriate candidates for LR.

Methods

Our transplant database and electronic medical records were searched for demographics and outcome measures.

Results

From 2000 to 2008, 81 children underwent liver transplantation from 37 LR and 44 CAD donors. There were no significant differences in graft or overall survival at 3 months or 1 year. The LR group was significantly younger (4.46 ± 5.2 years vs 7.41 ± 6.6 years; P = .03) and had a significantly lower PELD score (12.7 ± 13 vs 22 ± 12; P = .001) at the time of transplantation. Ten patients were transplanted for unresectable tumor in the LR group vs 4 CAD (P = .03). Significantly fewer LR recipients required return to the operating room in the first 30 days posttransplant (13.9% vs 34.1%; P = .03). The LR recipients had a higher rate of biliary stricture requiring reoperation (22.2% vs 2.3%; P = .005).

Conclusions

The LR liver transplantation is highly selected for patients with a parent donor who will need transplant but do not yet have a high PELD score. A lower PELD score at operation may have contributed to the lower incidence of postoperative complications requiring reoperation.     

Severe pulmonary hypertension in liver transplant candidates

Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n = 102; mean pulmonary artery pressure, > 25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n = 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n = 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n = 7; systolic pulmonary artery pressure, > 60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate. (Liver Transpl Surg 1997 Sep;3(5):494-500)