Severe Portopulmonary Hypertension Research Articles

Abstract 14822: Portopulmonary Hypertension Unveiled: Effects of Transjugular Intrahepatic Portopulmonary Shunt Placement

Introduction: Transjugular intrahepatic portosystemic shunts (TIPS) treat portal hypertension by connecting the portal vein to the hepatic vein in the liver. The resultant shunting of portal venous flow to the systemic circulation helps reduce the portosystemic gradient and is used to treat complications of portal hypertension. Right heart failure and the development of pulmonary hypertension after TIPS are known complications; however, portopulmonary hypertension (POPH) is rare. Description of Case: A 61-year-old male presents to the clinic for six months of exertional dyspnea, weight gain, and lower extremity edema. He has a history of coronary artery disease and nonalcoholic steatohepatitis cirrhosis, with TIPS placement four years prior for esophageal variceal bleeding. An echocardiogram revealed right ventricular (RV) dilatation with moderately reduced function, a flattened left ventricular septum, and an estimated pulmonary artery systolic pressure of 91 mmHg. An echocardiogram and right heart catheterization (RHC) performed before his TIPS showed normal RV function and pulmonary artery pressures (PAP). Decision Making: The patient was promptly started on furosemide and spironolactone, and after adequate diuresis, a repeat RHC was obtained, which showed significantly elevated PAP, and normal left-sided filling pressures and cardiac output. Other causes of pulmonary hypertension were ruled out, and the patient was started on tadalafil monotherapy for severe POPH, with significant improvement in his PAP (Table 1). Conclusion: POPH after TIPS is a rare complication that should be suspected in patients presenting with signs of right-sided volume overload. The mechanism by which TIPS leads to POPH is not entirely understood. The degree of RV dysfunction correlates with mortality, and prompt treatment is warranted.

Assessment and management of patients with portopulmonary hypertension undergoing liver transplantation

Portopulmonary hypertension (PoPH) is defined as the presence of otherwise unexplained pre-capillary pulmonary hypertension in patients with portal hypertension of cirrhotic or non-cirrhotic aetiology. PoPH occurs in at least 5–8.5% of patients being worked up for a liver transplant (LT) and its prevalence is thought to be increasing. Uncontrolled PoPH prior to LT is associated with high perioperative morbidity and mortality, with severe PoPH being considered a contraindication to LT. Early recognition and appropriate management of PoPH in patients being considered for LT is therefore imperative to achieve optimal outcomes. This review provides a detailed overview of: the epidemiology, prognosis and pathophysiology of PoPH; clinical assessment, screening and diagnostic approach; and pre-, peri‑ and post-transplant management of PoPH in patients undergoing LT. The current evidence base in this area is limited. This review particularly focuses on the evidence both supporting and challenging current practices and highlights areas for future research.

P9.49: Efficacy and Long-term Prognosis of Liver Transplantation For Porto-Pulmonary Hypertension

Objective: Porto-pulmonary hypertension (PoPH) refers to pulmonary hypertension based on severe portal hypertension. Severe PoPH has a very high perioperative mortality rate and is still considered a contraindication for liver transplantation (LT). We analyze efficacy and long-term prognosis of liver transplantation for porto-pulmonary hypertension from our center. Methods: A retrospective analysis was performed on 5 patients with PoPH who received liver transplantation in Beijing Friendship Hospital from Jan. 2013 to March 2022, in order to analyze postoperative follow-up results and long-term survival. Results: Five patients with PoPH with a mean age of 35.6 ± 18.6 years (60% females), were included in the analysis. Their primary diseases were hepatic spongiosis, Caroli disease, hepatitis B cirrhosis, drug-induced cirrhosis and primary sclerosing cholangitis. All patients were measured by Swan-Ganz catheterization of right heart, among them, the mean of the highest mean pulmonary artery pressure(mPAP) level before LT were 46.6mmHg(27-58mmHg). The mean of their highest systolic pulmonary artery pressure(SPAP) level measured under echocardiography was 101.36mmHg(51-154mmHg) before LT. The median Model for End-Stage Liver Disease (MELD) score was 16(14-20) at PoPH diagnosis. All patients had been on pulmonary vasodilator therapy(including ambrisentan, remodulin and sildenafil) for more than six months to lower pulmonary artery pressure to mPAP<35mmHg, that can achieve surgical indications before LT. The operations went smoothly, except in one case where pulmonary artery pressure suddenly increased during surgery ended smoothly after the addition of remodulin. Two patients underwent a second liver transplant at 6 months and 65 months postoperatively, and one patient died of acute heart failure after the second transplantation, while the remaining four patients survived. The follow-up time of the survived patients were 29.7, 46.9, 56, 85.2 months. The longest follow-up among them was over seven years. SPAP of them decreased 15.4, 129, 65.3, 20mmHg after LT. Two patient was discontinued pulmonary arterial pressure medications within 1 year after surgery because SPAP were down to normal, and other patients still on medication. Conclusion: Patients with pulmonary vasodilator therapy before LT can have excellent long-term outcomes post-transplant. Oral pulmonary vasodilator therapy can be effective treatment to qualify patients for LT.

Portopulmonary Hypertension: A Review of the Current Literature

Portopulmonary hypertension is defined as the development of pulmonary arterial hypertension in the setting of portal hypertension with or without liver cirrhosis. Portal hypertension-associated haemodynamic changes, including hyperdynamic state, portosystemic shunts and splanchnic vasodilation, induce significant alterations in pulmonary vascular bed and play a pivotal role in the pathogenesis of the disease. If left untreated, portopulmonary hypertension results in progressive right heart failure, with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and liver transplantation candidates, right heart catheterisation remains the gold standard for the diagnosis of the disease. Severe portopulmonary hypertension exerts a prohibitive risk to liver transplantation by conferring an elevated perioperative mortality risk. It is important for haemodynamic parameters to correspond with non-severe portopulmonary hypertension before patients can proceed with the liver transplantation. Small uncontrolled studies and a recent randomised controlled trial have reported promising results with vasodilatory therapies in clinical and haemodynamic improvement of patients, allowing a proportion of patients to undergo liver transplantation. In this review, the epidemiology, pathogenesis, diagnostic approach and management of portopulmonary hypertension are discussed. We also highlight fields of ongoing investigation pertinent to risk stratification and optimal patient selection to maximise long-term benefit from currently available treatments.

Association between the albumin-bilirubin (ALBI) score and severity of portopulmonary hypertension (PoPH): A data-mining analysis.

Portopulmonary hypertension (PoPH) is a severe complication of chronic liver disease. We aimed to investigate the etiology of chronic liver disease and the factors associated with the severity of PoPH. Echocardiography was undergone in 833 patients with chronic liver disease during 2005-2019 and 13 patients (1.6%) were diagnosed with PoPH in this observational study. At the diagnosis of PoPH, liver function was evaluated by albumin-bilirubin (ALBI) score. Severe PoPH was defined as (1) mean pulmonary arterial pressure (mPAP)≥50mmHg or (2) mPAP: 35-49mmHg and pulmonary vascular resistance≥400dyne/s/cm5 . Factors associated with severe PoPH were evaluated by decision-tree analysis. In patients with PoPH, the leading etiology of chronic liver disease was hepatitis C virus (HCV) (46.2% [sustained virological response (SVR): 23.1% and non-SVR: 15.4%]). Severe PoPH was observed in 53.8% of patients and the 5-year survival rate was 48.1%. There was a significant correlation of mPAP with ALBI score (r=0.6456, p=0.0171). In the decision-tree and random forest analyses, the most impacted classifier for severe PoPH was the ALBI score. In patients with ALBI score≥-1.45, all patients showed severe PoPH, while the prevalence of severe PoPH was 25.0% in patients with ALBI score<-1.45. We found that HCV including SVR was the major etiology of chronic liver disease in patients with PoPH. Moreover, we revealed that the ALBI score was the most impacted factor associated with severe PoPH. Thus, ALBI score may be useful for the estimation of pulmonary vascular resistance.

Planned Initiation of Venoarterial Extracorporeal Membrane Oxygenation Prior to Liver Transplantation in a Patient With Severe Portopulmonary Hypertension.

Planned Initiation of Venoarterial Extracorporeal Membrane Oxygenation Prior to Liver Transplantation in a Patient With Severe Portopulmonary Hypertension.

Living donor liver transplantation in a patient with severe portopulmonary hypertension.

Living donor liver transplantation in a patient with severe portopulmonary hypertension.

Pulmonary manifestations of chronic liver disease: a comprehensive review.

Hepatopulmonary syndrome (HPS) and porto-pulmonary hypertension (PoPH) represent relatively common pulmonary vascular complications of advanced liver disease. Despite distinct differences in their pathogenetic background, both clinical states are characterized by impaired arterial oxygenation and limited functional status, and are associated with increased pre-transplantation mortality. Accumulation of ascitic fluid in the pleural cavity, known as hepatic hydrothorax (HH), is another frequent manifestation of decompensated cirrhosis, which may cause severe respiratory dysfunction, depending on the volume of the effusion, the rapidity of its development and its resistance to therapeutic measures. Orthotopic liver transplantation constitutes the only effective treatment able to resolve the pulmonary complications of liver disease. A prioritization policy for liver transplantation has evolved over the past years regarding advanced stages of HPS, yielding favorable outcomes regarding post-transplantation survival and HPS resolution. In contrast, severe PoPH is associated with poor post-transplantation survival. Hence, liver transplantation is recommended only for patients with PoPH and an acceptable reduction in pulmonary pressure values, after receiving PoPH-targeted vasodilating therapy. This review focuses on basic pathogenetic and diagnostic principles and discusses the current therapeutic approaches regarding HPS, PoPH, and HH.

Liver transplantation for severe portopulmonary hypertension: A case report and literature review

Liver transplantation for severe portopulmonary hypertension: A case report and literature review

Sildenafil Monotherapy to Treat Portopulmonary Hypertension Before Liver Transplant

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.

Clinical and Haemodynamic Outcomes of the Macitentan Plus Tadalafil Combination for Severe Portopulmonary Hypertension: First Experience in Routine Clinical Practice

Clinical and Haemodynamic Outcomes of the Macitentan Plus Tadalafil Combination for Severe Portopulmonary Hypertension: First Experience in Routine Clinical Practice

P07-7 - The management of severe portopulmonary hypertension in patients undergoing liver transplantation

P07-7 - The management of severe portopulmonary hypertension in patients undergoing liver transplantation

The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation.

Severe portopulmonary hypertension (POPH) is a contraindication for liver transplantation (LT) because of the high risk of postoperative heart failure. The early detection of POPH is important for patients with biliary atresia (BA). Brain natriuretic peptide (BNP) is known to be correlated with liver fibrosis in patients with liver cirrhosis. The aim of this study was to elucidate the efficacy of BNP measurement for the follow-up of patients with BA. Thirty-two patients with BA were identified from September 2011 to December 2016. As indices of liver fibrosis/cirrhosis, APRI (P<.0001), FIB-4 (P<.0001), Child-Pugh score (P<.0001), IV collagen (P=.0005), and hyaluronic acid (P=.0291) had high or moderate correlations with BNP. Patients with splenomegaly, esophageal varices, liver fibrosis, and collateral veins had significantly higher BNP levels than those without. Patients diagnosed with POPH had significantly higher BNP levels in comparison with those patients without (P=.0068). In contrast, PELD/MELD scores showed an almost negligible correlation with the BNP level. LT was successful in 3 asymptomatic BA patients with POPH who had high BNP levels despite the low PELD/MELD scores. In conclusion, routine serum BNP surveillance can be easy to predict asymptomatic POPH. This may help to identify POPH before it reaches a stage that would contraindicate LT.

The management of severe portopulmonary hypertension in patients undergoing liver transplantation

The management of severe portopulmonary hypertension in patients undergoing liver transplantation

Portopulmonary hypertension: Updated review

Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain.

Portopulmonary hypertension: Still an appropriate consideration for liver transplantation?

Liver transplantation (LT) in patients with portopulmonary hypertension (PoPH) has historically resulted in unpredictable and often poor outcomes. The United Kingdom experience for the period 1992-2012 is reported in this article. A retrospective analysis of patients, preoperatively fulfilling the PoPH European Respiratory Society Task Force on Pulmonary-Hepatic Vascular Disorders diagnostic criteria was conducted across all UK LT centers. Data collection included comorbidities, use of preoperative and postoperative pharmacotherapy, patient survival, and cause of death. To enable survival stratification, PoPH was classified as mild, moderate, or severe based on mean pulmonary pressure of <35 mm Hg, 35-49 mm Hg, and ≥50 mm Hg, respectively. Of 127 patients reported to have PoPH, just 28 fulfilled the diagnostic criteria (14 mild, 9 moderate, 5 severe). Twenty (71.4%) patients were male with median age and Model for End-Stage Liver Disease of 50 years (range, 23-62 years) and 18 (range, 6-43), respectively. Twelve (42.9%) patients died within 5 years of LT. The majority of deaths (10 of 12; 83%) occurred within the first 6 months after LT, aetiologies of which included right heart failure (n = 3), progressive PoPH (n = 2), and sepsis (n = 2). Of those receiving preoperative pharmacotherapy (n = 8), 5 are currently alive and were classified as mild to moderate PoPH. Both severe PoPH patients optimized preoperatively with pharmacotherapy died within a year of LT. Development of effective vasodilatory therapies in the setting of pulmonary arterial hypertension has led to a dramatic improvement in patient survival. The available data indicate that in this era of pharmacotherapy, PoPH in isolation no longer represents a valid consideration to transplant. Liver Transplantation 22 1637-1642 2016 AASLD.

What do we take consideration in the patient who has an unpredicted severe portopulmonary hypertension in liver transplantation?: a case report.

Severe portopulmonary hypertension (PPHT) is considered a contraindication for liver transplantation (LT) because of the associated high mortality and poor prognosis. We report the case of a 57-year-old cirrhotic woman with severe PPHT (mean pulmonary artery pressure [mPAP] > 65 mmHg), who underwent a successful living donor LT. Intra-operative use of inhaled iloprost, milrinone, dobutamine, and postoperative use of inhaled nitric oxide and oral sildenafil failed to lower the pulmonary artery pressure (PAP). The patient responded only to nitroglycerin and drainage of massive ascites. Meticulous intra-operative volume control, which included minimizing blood loss and subsequent transfusion, was carried out. The use of vasopressors, which may have elevated the PAP, was strictly restricted. Intra-operative PAP did not show an increase, and the hemodynamics was maintained within relatively normal range, compared to the preoperative state. The patient was discharged without any complications or related symptoms.

Portopulmonary Hypertension: An Effect of Vasomodulation and Mortality Post-Transplant

Introduction: Portopulmonary hypertension (PPH) complicates the perioperative conditions in patients who anticipate orthotopic liver transplant (OLT). PPH is rare-occurring in only 6% of those referred for OLT. There is decrease in survival with the moderate to severe PPH subgroup with OLT. Overall only a third live to 5 years time after transplant. Treatment of PPH with vasomodulative therapies before transplantation has increased survival both pre- and post-transplant. The purpose of this study is to report the mortality, prevalence of vasomodulator therapy in PPH before and after OLT depending on group severity. Methods: This is a retrospective cohort study conducted from our liver transplant database over the course of 15 years. Patients were selected if they were diagnosed with PPH and received OLT. There pulmonary pressures were recorded preoperatively thereby categorizing patients into severity stages. Patient age, ethnicity, gender, BMI, and concurrent comorbidities were also included. The outcomes were overall and group-specific survival, and vasomodulator therapy types used. Results: The most common cause of liver failure in both groups was Hepatitis C and alcohol-induced cirrhosis. Overall mortality was 50%. There was an increase in use of sildenafil and epoprostenol post-transplant in the PPH group. Forty-percent of transplanted patients lived to more than 1200 day end-point. Patients in moderate to severe had a sustained survival rate from years 1-5 post-transplant. Conclusions: Patients with pulmonary vascular disease have a complicated liver transplant course specifically with moderate to severe PPH. This retrospective study suggests that in the setting of PPH and liver transplant, mortality is greatly improved after OLT with long-term treatment with vasomodulators, specifically those with moderate-severe disease.

Long-term follow-up of portopulmonary hypertension patients after liver transplantation

Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) ≥ 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single-center series have demonstrated the feasibility and short-term efficacy of OLT after POPH is controlled with vasodilators, but long-term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty-eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to ≤35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long-term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled with oral vasodilators.

Pulmonary complications in chronic liver disease.

The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders. HPS is the most common condition, found in 5%-30% of cirrhosis patients, manifested by abnormal oxygenation due to the development of intrapulmonary vascular dilatations. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation (LT). POPH is characterized by development of pulmonary arterial hypertension in the setting of portal hypertension, and is present in 5%-10% of cirrhosis patients evaluated for LT. Screening for POPH in cirrhosis patients eligible for LT is critical since severe POPH is a relative contraindication for LT. Patients with moderate POPH, who respond adequately to medical therapy, may benefit from LT, although sufficient controlled data are lacking. HH is a transudative pleural effusion seen in 5%-10% of cirrhosis patients, in the absence of cardiopulmonary disease. Diagnosis of HH should prompt consideration for LT, which is the ultimate treatment for HH. Conservative management includes salt restriction and diuretics, with thoracentesis and transjugular intrahepatic portosystemic shunt (TIPS) as second-line therapeutic options.