Pulmonary Assessment of the Liver Transplant Recipient

Abstract

Respiratory symptoms and hypoxemia can complicate chronic liver disease and portal hypertension. Various pulmonary disorders affecting the pleura, lung parenchyma, and pulmonary vasculature are seen in end-stage liver disease, complicating liver transplantation (LT). Approximately 8% of cirrhotic patients in an intensive care unit develop severe pulmonary problems. These disorders affect waiting list mortality and posttransplant outcomes. A thorough history, physical examination, and appropriate laboratory tests help diagnose and assess the severity to risk stratify pulmonary diseases before LT. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH) are respiratory consequences specific to cirrhosis and portal hypertension. HPS is seen in 5-30% of cirrhosis cases and is characterized by impaired oxygenation due to intrapulmonary vascular dilatations and arteriovenous shunts. Severe HPS is an indication of LT. The majority of patients with HPS resolve their hypoxemia after LT. When pulmonary arterial hypertension occurs in patients with portal hypertension, it is called POPH. All other causes of pulmonary arterial hypertension should be ruled out before labeling as POPH. Since severe POPH (mean pulmonary artery pressure [mPAP] >50 mm Hg) is a relative contraindication for LT, it is crucial to screen for POPH before LT. Those with moderate POPH (mPAP >35 mm Hg), who improve with medical therapy, will benefit from LT. A transudative pleural effusion called hepatic hydrothorax (HH) is seen in 5-10% of people with cirrhosis. Refractory cases of HH benefit from LT. In recent years, increasing clinical expertise and advances in the medical field have resulted in better outcomes in patients with moderate to severe pulmonary disorders, who undergo LT.

Keywords: hepatic hydrothorax; hepatopulmonary syndrome; liver transplantation; portopulmonary hypertension; pulmonary artery hypertension.

Figure 1

Pulmonary evaluation in liver transplantation (LT): Pulmonary evaluation of a liver transplant recipient starts with thorough history and physical examination. Pulse oximetry is a cost-effective method to screen for hypoxemia. All patients undergo CXR, ECG, ABG, 6-MWT, TTE, CE TTE, and HRCT as part of pretransplant evaluation. RHC, 99Tc MAA scan and pulmonary angiography are reserved for select cases. LT, liver transplantation; CXR, chest X-ray; ECG, electrocardiogram; ABG, arterial blood gas; 6-MWT, 6 -min walk test; P [A–a], pulmonary alveolar arterial pressure gradient; RVSP, right ventricular systolic pressure; IPVDs, intrapulmonary vascular dilatations; TTE, transthoracic echocardiogram; CE TTE, contrast-enhanced transthoracic echocardiogram; HRCT, high-resolution computed tomography; RHC, right heart catheterization; 99Tc MAA, scan technetium 99 macroaggregated albumin scintigraphy.

Figure 2

Pathophysiology of hepatopulmonary syndrome: Portal hypertension leads to an increased hyperdynamic circulatory state and shear stress which, along with chronic inflammation and oxidative stress, leads to dysregulation of key regulators of pulmonary vascular tone resulting in pulmonary vasodilatation and intrapulmonary shunts. Excess Vascular endothelial growth factor leads to angiogenesis which contributes to arteriovenous shunts and impaired oxygenation. Chronic inflammation also leads to increased intrapulmonary monocytes, which increase excess NO and CO, further contributing to vasodilatation. Adapted with permission from Machicao VI et al.3 andRodriguez-Roisin R et al. ET-1, endothelin-1; TNF, tumor necrosis factor; HO-1, heme oxygenase-1; CO, carbon monoxide; NO, nitric oxide; VEGF-A, vascular endothelial growth factor-A; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; ETB, endothelin B receptor; VEGFR2, vascular endothelial growth factor receptor 2.

Figure 3

Approach to hepatopulmonary syndrome (HPS): Pulse oximetry is the simplest and cost-effective method to screen for HPS. All patients undergo CE TTE as part of pretransplant evaluation. When there are competing etiologies for hypoxemia, 99TC MAA scan is done to quantify the shunt fraction and to a confirm HPS as the cause for hypoxemia. Pulmonary angiography is reserved for patients identified to have discrete shunts on CT chest that can be embolized. CE TTE, contrast-enhanced transthoracic echocardiography; ABG, arterial blood gas; IPVD, intrapulmonary vascular dilatations; P [A–a], pulmonary alveolar arterial oxygen gradient; CXR, chest X-ray; PFT, pulmonary function test; CT, computed tomography.

Figure 4

Pathogenesis of portopulmonary hypertension: Portal hypertension leads to an increased hyperdynamic circulatory state and shear stress along with chronic inflammation and oxidative stress leading to dysregulation of key regulators of pulmonary vascular tone resulting in pulmonary vasoconstriction. At the same time, damage to the pulmonary endothelium and the underlying smooth muscle along with genetic factors, results in permanent vascular remodeling, ultimately leading to the development of pulmonary hypertension. Adapted with permission from Thomas C et al. CO, cardiac output; NO, nitric oxide; ET-1, endothelin-1; TXA2, thromboxane A2; 5-HT, serotonin; E2, estrogen; BMP9, bone morphogenic protein 9; BMPR2, bone morphogenic receptor 2.

Figure 5

Approach to portopulmonary hypertension: TTE, transthoracic echocardiogram; POPH, portopulmomary hypertension; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; RHC, right heart catheterization. ∗AASLD guidelines recommend RHC if mPAP >45 mmHg while ILTS recommends RHC if mPAP >50 mmHg.

Figure 6

Hemodynamic patterns on right heart catheterization in cirrhosis patients with elevated RVSP on echocardiogram.