Guideline sources The following summarized guidelines for the evaluation and management of portopulmonary hypertension (POPH) are prepared by our editorial team based on guidelines from the Society of Critical Care Medicine (SCCM 2020), the European Association for the Study of the Liver (EASL 2018), the International Liver Transplantation Society (ILTS 2016), and the American Association for the Study of Liver Diseases (AASLD 2014). 1 2 3 4 Guidelines 1. Screening and diagnosis Indications for testing: Obtain Doppler transthoracic echocardiography to screen for POPH in patients with portal hypertension being candidates for TIPS insertion or liver transplantation. B Obtain repeated screening for POPH in patients with portal hypertension while waiting for liver transplantation. B https://web.pathway.md/diseases/recJbc4r91Mt8HEUv 1/5 6/29/23, 11:20 PM Portopulmonary hypertension Pathway Recognize that female gender and autoimmune liver diseases are risk factors for POPH, but do not use these for screening. B Diagnostic criteria: use the ERS diagnostic criteria of POPH in research and clinical settings. B Differential diagnosis: exclude other causes of pulmonary hypertension in the setting of liver disease. B 2. Classification and risk stratification Severity assessment: Consider describing the severity of POPH in terms of mean pulmonary artery pressure (assuming increased pulmonary vascular resistance) as follows: Situation Guidance 25-34 Mild 35-44 Moderate 45. B Severe 3. Diagnostic investigations Echocardiography: As per EASL 2018 guidelines: Obtain Doppler TTE to screen for POPH in patients deemed potential recipients for TIPS or liver transplantation. B Obtain repeated echocardiography in patients with POPH listed for transplantation. B As per AASLD 2014 guidelines, exclude POPH in liver transplant candidates by routine echocardiography. B Vasoreactivity testing: do not obtain acute vasoreactivity testing during right heart catheterization to guide treatment in POPH. D 4. Diagnostic procedures Right heart catheterization: As per EASL 2018 guidelines, perform right heart catheterization in patients with a positive screening echocardiogram. B As per ILTS 2016 guidelines, perform right heart catheterization to confirm hemodynamics consistent with the diagnosis of POPH: mean pulmonary artery pressure > 25 mmHg pulmonary vascular resistance > 3 wood units (240 dyne s/cm ) pulmonary artery wedge pressure < 15 mmHg. B https://web.pathway.md/diseases/recJbc4r91Mt8HEUv 2/5 6/29/23, 11:20 PM Portopulmonary hypertension Pathway As per AASLD 2014 guidelines, perform right heart cardiac catheterization in patients with RV systolic pressure 45 mmHg. B 5. Medical management PAH-specific pharmacotherapy: As per SCCM 2020 guidelines, consider treating POPH with agents approved for pulmonary arterial hypertension in patients with mean pulmonary artery pressure > 35 mmHg. C As per EASL 2018 guidelines, consider offering therapies approved for primary pulmonary arterial hypertension in patients with POPH to improve exercise tolerance and hemodynamics. Be cautious when using endothelin antagonists because of concerns over hepatic impairment. B As per ILTS 2016 guidelines, consider offering agents approved for pulmonary artery hypertension to improve hemodynamics and exercise capacity in patients with POPH. B Medications to avoid: As per EASL 2018 guidelines, discontinue -blockers in patients with proven POPH and manage varices by endoscopic therapy. B As per ILTS 2016 guidelines, do not use anticoagulation in patients with POPH. D Show 2 more 6. Therapeutic procedures Transjugular intrahepatic portosystemic shunt: As per EASL 2018 guidelines, do not perform TIPS placement in patients with POPH. D As per ILTS 2016 guidelines, do not perform elective TIPS placement in patients with severe POPH (mean pulmonary artery pressure 45-50 mmHg). D Extracorporeal membrane oxygenation: consider performing ECMO if an acute rise in mean pulmonary artery pressure occurs at reperfusion and RV dysfunction occurs. C Right ventricular assist device: do not use RV assist devices in patients with POPH due to the potential for pulmonary artery rupture. D 7. Perioperative care Perioperative monitoring: obtain pulmonary artery catheter monitoring before and during liver transplantation in all adult patients. B Show 2 more Perioperative medical therapy: administer pulmonary artery hypertension-targeted therapy continuously during liver transplantation. B Show 3 more Postoperative evaluation: https://web.pathway.md/diseases/recJbc4r91Mt8HEUv 3/5 6/29/23, 11:20 PM Portopulmonary hypertension Pathway Do not perform routine post-liver transplantation right heart catheterization unless clinically indicated. D Obtain Doppler TTE every 3 months to guide weaning decisions. B 8. Surgical interventions Liver transplantation: As per EASL 2018 guidelines, consider performing liver transplantation if mean pulmonary arterial pressure is < 35 mmHg and RV function is preserved. Do not perform liver transplantation in patients with a mean pulmonary arterial pressure of 45 mmHg, irrespective of applied therapy. B Show 3 more As per ILTS 2016 guidelines, insufficient evidence to support the concept that POPH (treated or untreated) is an indication for liver transplantation. I Show 4 more As per AASLD 2014 guidelines: Potential recipients with POPH should be evaluated by a pulmonary or cardiac specialist for vasodilator therapy. B LT can be offered to potential recipients with POPH, which responds to medical therapy with an MPAP 35 mmHg. B 9. Follow-up and surveillance Serial clinical assessment: obtain clinical monitoring of cardiac function and for complications of liver disease. B Clinical findings Symptoms Past medical history Chest pain Hepatopulmonary syndrome Dyspnea Portal hypertension Fatigue Vascular exam Palpitations Syncope Peripheral edema Vital signs Abdominal exam Hypoxemia Ascites O2 saturation Cardiac exam Accentuated P2 sound Parasternal heave https://web.pathway.md/diseases/recJbc4r91Mt8HEUv 4/5 6/29/23, 11:20 PM Portopulmonary hypertension Pathway References 1. Michael J Krowka, Michael B Fallon, Steven M Kawut et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016 Jul;100 7 1440 52. Open 2. Paul Martin, Andrea DiMartini, Sandy Feng et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59 3 1144 65. Open 3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69 2 406 460. Open 4. Rahul Nanchal, Ram Subramanian, Constantine J Karvellas et al. Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU Cardiovascular, Endocrine, Hematologic, Pulmonary and Renal Considerations: Executive Summary. Crit Care Med. 2020 Mar;48 3 415 419. Open https://web.pathway.md/diseases/recJbc4r91Mt8HEUv 5/5