Pulmonary vascular abnormalities in cirrhosis

doi:10.1016/j.bpg.2006.07.011

Best Practice & Research Clinical Gastroenterology

Volume 21, Issue 1, 2007, Pages 141-159

https://doi.org/10.1016/j.bpg.2006.07.011 Get rights and content

Two pulmonary vascular disorders can occur in liver disease and/or portal hypertension: the hepatopulmonary syndrome (HPS), which is characterized by intrapulmonary vascular dilatations, and portopulmonary hypertension (POPH), in which pulmonary vascular resistance is elevated. POPH and HPS are characterized by distinct pulmonary microvascular remodelling, which occurs at different anatomical sites of the pulmonary microcirculation. The exact pathophysiological mechanisms of these pulmonary vascular disorders are unknown. However, as HPS and POPH have been reported in patients with extrahepatic portal hypertension, the factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in HPS and hemodynamic failure in POPH. The severity of HPS seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of POPH. Resolution of HPS is common after liver transplantation, which has an uncertain effect in POPH.

Section snippets

INTRODUCTION

The liver is unique as an organ: it is connected in series with the lung and portal system. It receives all the venous effluent from the portal system and directs its metabolites to the lungs before perfusing any other organ in the body. In liver diseases and/or portal hypertension, the pulmonary vascular endothelium can be directly injured by constituents of venous blood arising in the liver and portal system. This explains the frequent pulmonary vascular abnormalities seen in these diseases.

PATHOPHYSIOLOGY OF HPS AND POPH: IMPLICATIONS OF THE LIVER AND PORTAL CIRCULATION IN THE CONTROL OF THE PULMONARY AND SYSTEMIC ANGIOGENESIS AND VASOREACTIVITY

A number of clinical and pathological observations support the view that, in liver diseases and/or portal hypertension, the liver and the portal system regulate vasoreactivity and angiogenesis in both the pulmonary and systemic circulations.

A hyperdynamic circulatory state with high cardiac output and low systemic and pulmonary vascular resistances (PVRs) is present in 50% of patients with cirrhosis and in animal with experimental cirrhosis or portal hypertension.² The severity of cirrhosis,

Definition¹

POPH can be defined as a pulmonary arterial hypertension associated with portal hypertension, with or without hepatic disease. Diagnosis of POPH is based on pulmonary hemodynamic criteria obtained via right heart catheterization, as defined at the third World Symposium on Pulmonary Arterial Hypertension.¹⁵ Diagnostic criteria for pulmonary arterial hypertension include a mean pulmonary arterial pressure (PAP) of >25 mmHg (at rest) or >30 mmHg (during exercise), with a mean pulmonary artery

Definition and frequency of HPS¹

HPS is defined as a defect in arterial oxygenation induced by intrapulmonary vascular dilatations (IPVD) associated with hepatic disease. The vascular component characteristically includes diffuse or localized dilated pulmonary capillaries and, less commonly, pleural and pulmonary arteriovenous communications. HPS associates a clinical triad characterized by arterial deoxygenation, IPVD and liver disorder or portal hypertension.¹

The pulmonary gas exchange abnormality is characterized by

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Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for “equity”, trying to save every patient, regardless of the overall utility; and “efficiency”, rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose “absolute” and “relative” conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates.
Hepatopulmonary Syndrome and Portopulmonary Hypertension
2017, Liver Pathophysiology: Therapies and Antioxidants
This chapter focuses on two cardiopulmonary vascular disorders of liver disease: hepatopulmonary syndrome (HPS) and portopulmonary hypertension. HPS is characterized by gas exchange disturbances due to pulmonary vasodilation and right-to-left shunting, whereas portopulmonary hypertension is defined by pulmonary hypertension secondary to increased pulmonary vascular resistance, which may lead to hemodynamic failure. Key aspects of assessment include active screening with echocardiography, right heart catheterization, and arterial blood gas analysis, early diagnosis, and prompt referral to specialized hepatology centers. As no curative medical treatment is available and only liver transplantation may lead to resolution, MELD exceptions can be allocated to provide prioritization for transplantation. This chapter will give an overview on diagnosis and screening, pathophysiology and pathogenesis, therapeutic targets, and treatment of both conditions.
Complications of Cirrhosis: Introduction. Introduction
2017, Liver Pathophysiology: Therapies and Antioxidants
Fibrosis frequently leads to cirrhosis, the final stage of liver damage. There are several complications of cirrhosis, of note: portal hypertension (PHT), gastroesophageal varices, ascites, hepatorenal syndrome (HRS), hepatic encephalopathy (HE), hepatopulmonary syndrome, and hepatocellular carcinoma. Understanding the pathogenesis of PHT could be of great utility in preventing and curing the complications of PHT, such as esophageal varices, HE, and ascites. When cirrhosis is advanced, splanchnic arterial vasodilatation is so intense that the effective arterial blood volume becomes markedly reduced and the arterial pressure falls. In the late stages of cirrhosis, there is a reduction in cardiac output (possibly related to cirrhotic cardiomyopathy); as a consequence, there is homeostatic activation of vasoconstrictor and antinatriuretic factors to control arterial pressure results, leading to renal sodium and fluid retention. HRS is a potentially reversible condition that occurs in patients with ascites.
Evaluation of Arteriovenous Shunting in Patients with End-Stage Liver Disease: Potential Role of Early Right Heart Catheterization
2015, Transplantation Proceedings
Citation Excerpt :
A few case reports have described a transition from HPS to PoPH or from PoPH to HPS [23,24], and another the presence of both syndromes in the same patient [21]. Because both syndromes are thought to be caused by the release of vasoactive mediators from the portal endothelium [25], the simultaneous elaboration of both vasodilatory and vasoconstrictive mediators would seem to be paradoxic. Either dysregulation of a shared vascular signaling pathway, which may lead to either pulmonary vasoconstriction or vasodilation, or preferential binding of endothelin (ET) 1 to either the ET-1A or the ET-1B receptor, resulting in vasoconstriction or vasodilation, respectively, may be the explanation [26].
In patients with end-stage liver disease (ESLD), the presence of hypoxemia suggests the presence of intrapulmonary oxygen shunting (IPS) and/or transatrial shunting. Early identification of each is imperative to avoid potentially fatal peritransplantation complications and appropriately prioritize patients for liver transplantation (LT). The aim of this work was to compare the sensitivity of transthoracic echocardiography (TTE) and right heart catheterization (RHC) with intracardiac echocardiography (ICE) for identifying the etiologies of resting hypoxemia in patients with ESLD being evaluated for LT.
Records of 28 patients with ESLD and resting hypoxemia who underwent TTE with bubble study and RHC/ICE were reviewed. Patients with a patent foramen ovale (PFO) were compared with non-PFO patients to determine diagnostic accuracy of TTE with bubble study versus RHC/ICE.
TTE with bubble study diagnosed PFO, IPS, and pulmonary hypertension (PH), respectively, with sensitivities of 46%, 41%, and 25% and specificities of 46%, 45%, and 80% compared with RHC/ICE. Although IPS detected by RHC/ICE was more common in patients without a PFO (92%), 5 patients with a PFO (33%) also had IPS (P = .002). Isolated PH was detected exclusively in patients with a PFO (5/15; 33%).
TTE with bubble study is neither sensitive nor specific to exclude a PFO in patients with ESLD. RHC/ICE is a safe and accurate diagnostic/interventional modality in this group of patients and is useful to diagnose other comorbidities, such as IPS and PH, that may coexist and contribute to resting hypoxemia.
Hepatopulmonary syndrome in the era of hepatic transplantation
2017, Acta Colombiana de Cuidado Intensivo
La complicación pulmonar más común de la enfermedad hepática es la alteración del intercambio de gaseoso que resulta en hipoxemia grave, factor que altera el curso clínico de los pacientes con cirrosis hepática. Una de estas alteraciones es el síndrome hepatopulmonar, que se asocia con un aumento significativo de la morbimortalidad y se define como una tríada que incluye enfermedad hepática, oxigenación arterial anormal causada por dilataciones vasculares intrapulmonares demostrables, generando un verdadero shunt pulmonar y un desequilibrio en la difusión y perfusión. También puede encontrarse un aumento anormal de la resistencia vascular pulmonar como consecuencia de la obstrucción del flujo a nivel del lecho arteriolar pulmonar lo que resulta en hipertensión pulmonar clínica llamada «hipertensión portopulmonar», esta se asemeja a la hipertensión pulmonar primaria, con disnea y fatiga pero sin respuesta clínica ni histopatológica a terapias como prostaciclina. Estas 2 condiciones vasculares pulmonares (síndrome hepatopulmonar y la hipertensión portopulmonar) en pacientes cirróticos o con hipertensión portal pueden coexistir y, por lo general, el síndrome hepatopulmonar se desarrolla antes de la hipertensión portopulmonar.
Se cree que el síndrome hepatopulmonar es causado principalmente por 2 procesos centrales: vasodilatación y angiogénesis pulmonar, responsables de las alteraciones en el intercambio gaseoso, el desequilibrio en la ventilación-perfusión y la limitación de la difusión de oxígeno.
En la actualidad, este síndrome ha tomado especial interés en relación con el éxito del trasplante hepático. Aunque es infrecuente, es importante que se reconozca rápidamente su expresión clínica, entender la patogenia involucrada en el paciente con cirrosis hepática clínica, funcional e histológica, dado su curso progresivo y de mal pronóstico.
The most common pulmonary complication of liver disease is the disruption of gas exchange, resulting in severe hypoxemia, a factor that alters the clinical course of patients with liver cirrhosis. One of these alterations is the hepatopulmonary syndrome, which is associated with a significant increase in morbidity and mortality, and is defined as a triad that includes liver disease, abnormal arterial oxygenation caused by demonstrable intrapulmonary vascular dilations, with consequent pulmonary shunt, and imbalance in diffusion and perfusion. An abnormal increase in pulmonary vascular resistance may also be found as a consequence of pulmonary arteriolar flow obstruction, resulting in clinical pulmonary hypertension called “portopulmonary hypertension”. This resembles primary pulmonary hypertension, with dyspnoea and fatigue, but without clinical or histopathological responses to therapies such as prostacyclin. These two pulmonary vascular conditions (hepatopulmonary syndrome and portopulmonary hypertension) in cirrhotic patients, or with portal hypertension, may coexist in the same patient, and hepatopulmonary syndrome usually develops before portopulmonary hypertension.
Hepatopulmonary syndrome is thought to be mainly caused by two central processes: vasodilation and pulmonary angiogenesis, which are responsible for alterations in gas exchange, imbalance in ventilation-perfusion, and limitation of oxygen diffusion.
This syndrome has currently become of special interest in the success of liver transplantation. Although it is rare, it is important to rapidly recognise its clinical expression in order to understand the pathogenesis involved in the patient with clinical, functional, and histological liver cirrhosis, given its progressive course and poor prognosis.
Portopulmonary hypertension: Updated review
2018, Archivos de Cardiologia de Mexico
La hipertensión portopulmonar (HPP) es una entidad poco frecuente a nivel mundial, aunque se desconocen los datos epidemiológicos en México. Sin embargo, las enfermedades crónicas del hígado son muy prevalentes en mexicanos. La HPP es el 4.° subtipo en frecuencia del grupo de la hipertensión arterial pulmonar. Su diagnóstico está dentro de 2 escenarios: los pacientes con sospecha de hipertensión pulmonar y los candidatos a trasplante hepático ortotópico (THO). Tanto el ecocardiograma como el cateterismo cardiaco derecho son determinantes para el diagnóstico en ambos escenarios. La HPP es un reto para el THO, pues aumenta la mortalidad perioperatoria de manera importante. El uso de terapia específica es la piedra angular de este padecimiento, como una medida para poder mejorar el desenlace de los que llegan a ser candidatos a un THO con HPP moderada a grave. Es importante reconocer que la HPP puede llegar a ser una contraindicación para el THO. Hasta el momento el papel del trasplante combinado pulmón-hígado o corazón-pulmón-hígado como una medida de curación de la enfermedad vascular pulmonar en pacientes con HPP es incierto.
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.

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10Pulmonary vascular abnormalities in cirrhosis

Section snippets

INTRODUCTION

PATHOPHYSIOLOGY OF HPS AND POPH: IMPLICATIONS OF THE LIVER AND PORTAL CIRCULATION IN THE CONTROL OF THE PULMONARY AND SYSTEMIC ANGIOGENESIS AND VASOREACTIVITY

Definition1

Definition and frequency of HPS1

J Hepatol

Lancet

Ann Thorac Surg

Gastroenterology

Hepatology

Gastroenterology

Am J Cardiol

Lancet

Gastroenterology

Pulmonary-hepatic vascular disorders (PHD)

Eur Respir J

Pulmonary vascular disorders in portal hypertension

Eur Respir J

Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites

Gut

Role of nitric oxide in hepatopulmonary syndrome in cirrhotic rats

Am J Respir Crit Care Med

The hepatopulmonary syndrome: new name, old complexities

Thorax

10
Pulmonary vascular abnormalities in cirrhosis

Definition¹

Definition and frequency of HPS¹