Acute Respiratory Failure and Pulmonary Complications in End-Stage Liver Disease

Nida Qadir, MD; Tisha Wang, MD; Igor Barjaktarevic, MD, PhD; Steven Y. Chang, MD, PhD


Semin Respir Crit Care Med. 2018;39(5):546-555. 

In This Article

Portopulmonary Hypertension

PoPH is classified by the World Health Organization as Group 1 pulmonary hypertension (PH). Risk factors for developing PoPH include female sex and autoimmune hepatitis.[26] PoPH is currently diagnosed in patients with portal hypertension, with or without ESLD, who meet the following criteria: a mean pulmonary artery pressure (mPAP) of >25 mm Hg, a pulmonary vascular resistance (PVR) > 240 dynes·s·cm−5 (>3 Wood units), and a pulmonary artery occlusion pressure of ≤ 15 mm Hg. It is a diagnosis of exclusion, as other etiologies of abnormally elevated pulmonary pressures must be ruled out. PoPH is characterized by vascular abnormalities due to intimal proliferation, hypertrophy of the media, fibrosis, in situ thrombosis, and other changes not unlike idiopathic PH, with resultant increased PVR. Very likely, the factors contributing to the histologic changes result from increased blood flow through the pulmonary vasculature due to portal hypertension and the inability of the diseased liver to metabolize what could be otherwise physiological mediators and chemicals.

PoPH affects approximately 5% of patients diagnosed with pulmonary artery hypertension, while 2 to 6% of patients with portal hypertension are diagnosed with PoPH.[6,7,27] In the Registry to Evaluate Early and Long-term Pulmonary Artery Hypertension Disease Management (REVEAL Registry), PoPH was shown to have a higher 5-year mortality than idiopathic PH despite better hemodynamics and function at the time of diagnosis (60vs. 36%).[7] A 2017 study of 110 PoPH patients in the United Kingdom also showed dismal survival for PoPH patients with 5-year mortality of 65% despite receiving standardized advanced PH therapies.[8] DuBrock et al reviewed 190 OLT candidates with MELD exception points for PoPH. They found an unadjusted 1-year mortality or removal from waitlist because of deterioration of 11.1%. Overall waitlist mortality or removal from the waitlist was 23.2% after a median of 344 days. Predictors of mortality while awaiting OLT included age, native MELD score, and initial PVR. This same study examined outcomes post-OLT and showed that 75% of patients were still alive at last follow-up.[28]

Although clinical trials of advanced PH therapies (prostanoids, endothelin receptor antagonists, and phosphodiesterase -5 inhibitors) have excluded patients with PoPH, it is generally accepted that PoPH patients should be treated with these medications, in addition to diuretic therapy, especially as a bridge to OLT.[29] Unfortunately, mortality for these patients remains high. Verma et al in 2016 showed that PoPH patients who undergo OLT still have high mortality, with 12/28 (43%) patients dying after transplant by 5 years.[9] Risk stratification of these patients is important, as those patients with uncontrolled hemodynamics despite aggressive advanced PH management have unacceptably high mortality. It appears that it is likely safe to transplant candidates with PoPH who have a mPAP ≤ 35 mm Hg with a PVR ≤ 400 dynes·s·cm−5 (≤ 5 Wood units), and this is reflected in the MELD exception program in the United States, in which these patients are granted points to gain priority on the waitlist. Patients with a mPAP >35 mm Hg have an elevated risk of post-OLT mortality, and most centers do not transplant those with a mPAP of >50 mm Hg.[30] Currently, PoPH, by itself, is not uniformly considered an absolute indication for OLT given the unpredictability and poor outcomes even after transplant.[9,30] Patients with PoPH who have other indications for OLT should be treated with advanced PH therapies as needed to achieve hemodynamics required for safe OLT.

If patients need to undergo OLT, they should remain on their PH treatment. The most concerning intraoperative issues are hemodynamic instability and right ventricular (RV) failure from reperfusion, given that a dysfunctional RV has to adequately handle a large increase in blood volume. Intraoperative management might include monitoring via transesophageal echocardiography and pulmonary artery catheter. Inhaled NO can be used intraoperatively to stabilize patients who deteriorate.[31] Other treatment modalities that can be used in the peri- or intraoperative setting include intravenous prostanoids, milrinone, and possibly extracorporeal membrane oxygenation.[30] Postoperatively, advanced PH therapies should be continued. For those who undergo and survive OLT, there is often a transient worsening of hemodynamics post-OLT.[29] Many patients can eventually undergo down-titration of advanced PH therapies, but frequently remain on some PH-specific therapy for months to years.[30]

One and 3-year survival for PoPH patients who undergo OLT is 85 and 81%,[32] while 5-year survival is approximately 57%.[9] As a comparison, survival for all primary liver transplant patients in the United States at 1, 3, and 5 years is 91.8, 83.8, and 76.1%, respectively.[33] Improvements in survival for PoPH patients will depend on advances in PH treatments and general OLT management, as well as better patient selection.