Hepatopulmonary syndrome and portopulmonary hypertension

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hepatopulmonary syndrome (HPS) is a gas-exchange disorder caused by intrapulmonary vascular dilatation and shunting in the setting of liver disease or portal hypertension. Dilated capillaries permit blood to pass too far from alveolar oxygen or too quickly for complete equilibration. Patients develop exertional dyspnoea, cyanosis or low saturation, often worse when upright. Pulse oximetry is a useful prompt, but arterial blood gas analysis, including the alveolar–arterial oxygen gradient, defines the oxygenation defect. Contrast transthoracic echocardiography demonstrates intrapulmonary passage; it does not measure hypoxaemia severity.

Portopulmonary hypertension (PoPH) is a different problem: precapillary pulmonary arterial hypertension in a person with portal hypertension. Pulmonary vascular resistance rises, progressively loading the right ventricle. Exertional breathlessness, fatigue, chest discomfort, presyncope, a loud pulmonary component of the second heart sound and right-heart failure are possible. Cirrhosis itself can produce high cardiac output or fluid overload with raised pulmonary pressure, so right-heart catheterisation is essential to measure mean pulmonary arterial pressure, pulmonary arterial wedge pressure, pulmonary vascular resistance and cardiac output before the label is accepted.

The distinction changes transplant strategy. HPS generally improves after liver transplantation and may qualify for consideration under the current NHSBT selection policy, although peri-operative risk rises with severe hypoxaemia. Untreated severe PoPH creates high peri-operative right-ventricular risk and can contraindicate transplantation; carefully selected patients may become eligible after haemodynamic optimisation in a pulmonary-hypertension centre. Decisions must use current NHSBT policy rather than memorised historical cut-offs, with both liver and pulmonary teams reviewing trajectory rather than a single test.

Key points

Hepatopulmonary syndrome combines liver disease or portal hypertension, intrapulmonary vascular dilatation and an objectively demonstrated oxygenation defect.
Platypnoea and orthodeoxia favour hepatopulmonary syndrome because upright posture increases blood flow through basal dilated pulmonary vessels.
Agitated-saline contrast appearing in the left heart after a delayed passage supports intrapulmonary shunting; immediate passage suggests an intracardiac communication.
Portopulmonary hypertension is pulmonary arterial hypertension associated with portal hypertension and requires right-heart catheterisation for haemodynamic confirmation.
Echocardiography is a screening and right-heart assessment tool; it cannot by itself distinguish precapillary disease from high-output or volume-overloaded states.
Supplemental oxygen supports hypoxaemic hepatopulmonary syndrome, but liver transplantation is the only established treatment capable of reversing the underlying vascular syndrome.
Portopulmonary hypertension treatment belongs in a designated pulmonary-hypertension service because drug selection, hepatic metabolism and transplant thresholds are tightly linked.
Both conditions can occur without a direct relationship to conventional liver-test severity, so persistent unexplained dyspnoea deserves purposeful investigation.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Portal-hypertensive vascular signalling

Cirrhosis or non-cirrhotic portal hypertension can alter pulmonary vascular mediators, producing either dilatation or proliferative vasoconstriction in susceptible individuals.

Hepatopulmonary phenotype

Intrapulmonary vascular dilatation develops in a subset of people with liver disease, without severity tracking routine liver tests reliably.

Portopulmonary phenotype

Pulmonary arterial remodelling associated with portal hypertension is distinct from simple hyperdynamic flow and requires haemodynamic confirmation.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Pulmonary vessel dilatation
In hepatopulmonary syndrome, dilated basal capillaries place red cells too far from alveolar oxygen and permit functional intrapulmonary shunting.
2
Impaired oxygenation
Ventilation-perfusion mismatch and diffusion limitation worsen upright as blood preferentially reaches dilated basal vessels, producing orthodeoxia and platypnoea.
3
Pulmonary arterial remodelling
In portopulmonary hypertension, vasoconstriction and vascular proliferation raise pulmonary resistance, progressively loading and failing the right ventricle.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Platypnoea and orthodeoxia

Breathlessness or oxygen saturation worsening on sitting or standing and improving supine is characteristic of HPS, although formal measurements and exclusion of other shunts remain necessary.

Hypoxaemic stigmata

Cyanosis, digital clubbing and numerous spider naevi may accompany HPS. Their absence does not exclude early disease, and anaemia can alter the clinical appearance.

Pulmonary hypertension symptomsRed flag

Exertional dyspnoea, chest pressure, presyncope or syncope, ankle swelling and declining exercise capacity suggest right-ventricular stress and require specialist investigation.

Right-heart findings

A parasternal heave, loud P2, raised jugular venous pressure, tricuspid regurgitation murmur or ascites out of proportion to hepatic change supports advanced PoPH but overlaps with other cardiopulmonary disease.

Transplant assessment discovery

Both syndromes may be detected during formal transplant work-up before prominent symptoms. A normal resting conversation does not exclude exertional desaturation or abnormal pulmonary haemodynamics.

Acute decompensation warningRed flag

Sudden hypoxaemia, pleuritic pain or rapid right-heart deterioration is not a routine evolution of either syndrome; investigate pulmonary embolism, infection, fluid overload and bleeding urgently.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Pulse oximetry supine and uprightFirst step
Why
Screen for hypoxaemia and document a clinically relevant postural change.
Interpretation and limitations
A fall when upright supports orthodeoxia but is not diagnostic. Normal pulse oximetry may miss an increased alveolar–arterial gradient, and dyshemoglobinaemia or poor perfusion can distort readings.
02
Arterial blood gas on room air
Why
Measure arterial oxygenation and calculate the alveolar–arterial oxygen gradient for HPS assessment.
Interpretation and limitations
An increased age-adjusted gradient in the appropriate liver context supports impaired gas exchange; PaO2 grades severity. Oxygen therapy and posture must be recorded so results are interpretable.
03
Agitated-saline contrast echocardiography
Why
Demonstrate right-to-left passage and distinguish intrapulmonary vascular dilatation from a likely intracardiac shunt.
Interpretation and limitations
Microbubbles appearing in the left atrium after several cardiac cycles favour intrapulmonary transit, whereas very early appearance favours an intracardiac defect. Timing is interpreted by experienced echocardiographers.
04
Standard transthoracic echocardiography
Why
Estimate pulmonary pressure, assess right-ventricular size and function, and screen transplant candidates for PoPH.
Interpretation and limitations
Raised estimated pressure or right-heart abnormalities justify referral, but echo cannot confirm pulmonary arterial hypertension or distinguish high-output circulation from elevated vascular resistance.
05
Right-heart catheterisation
Why
Confirm and phenotype pulmonary hypertension using direct haemodynamic measurements.
Interpretation and limitations
PoPH requires a precapillary pattern: raised mean pulmonary arterial pressure with elevated pulmonary vascular resistance and a non-elevated wedge pressure. Interpret using current specialist definitions and transplant policy.
06
Lung imaging and pulmonary function
Why
Identify alternative or additional explanations for hypoxaemia and dyspnoea.
Interpretation and limitations
CT, chest radiography, spirometry and gas transfer are selected by presentation. Emphysema, interstitial disease, effusion, embolic disease and infection can coexist and may dominate management.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Primary lung disease

Parenchymal abnormalities, obstructive physiology or infection on respiratory testing may explain hypoxaemia without delayed contrast passage or pulmonary arterial haemodynamics.

Intracardiac shunt

Immediate left-heart appearance of agitated saline suggests an atrial or ventricular communication, unlike delayed passage through dilated pulmonary vessels.

Left-heart or thromboembolic pulmonary hypertension

Raised left-sided filling pressures or chronic thromboembolic imaging distinguishes commoner causes from portopulmonary arterial disease during specialist haemodynamic assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01HPSConfirm oxygenation and shuntFirst stepA person with liver disease or portal hypertension has unexplained dyspnoea, low saturation or orthodeoxia.

1Measure saturation with posture, obtain a properly documented room-air arterial blood gas where safe, and investigate common lung, cardiac, anaemic and thromboembolic explanations in parallel.
2Arrange agitated-saline contrast echocardiography through an experienced service, interpreting delayed left-sided bubbles as evidence of intrapulmonary vascular passage in the correct clinical context.
3Provide oxygen when clinically indicated and refer early to the liver-transplant team because disease-modifying therapy, severity classification and selection exceptions require specialist assessment.

02PoPHEstablish pulmonary haemodynamicsScreening echo or symptoms suggest pulmonary hypertension in a person with portal hypertension.

1AlternativeAssess functional limitation, signs of right-heart failure and alternative causes, then refer to a designated pulmonary-hypertension service rather than prescribing empirical pulmonary vasodilators.
2Use right-heart catheterisation to separate increased vascular resistance from a high-output or fluid-overloaded circulation and to quantify right-ventricular risk relevant to treatment and transplantation.
3Let the specialist service select and monitor targeted therapy, considering hepatic function, interactions, pregnancy risk and the need for repeat haemodynamics before transplant decisions.

03CoordinateLink physiology to transplantationHPS or PoPH is confirmed in a current or potential liver-transplant candidate.

1Discuss the case jointly between the transplant and pulmonary-hypertension teams, using the current NHSBT Liver Selection Policy and recording whether the syndrome increases urgency or procedural risk.
2For HPS, trend oxygenation and functional status while providing supportive oxygen; for PoPH, document treatment response with specialist testing rather than relying on symptom improvement alone.
3Reassess eligibility whenever haemodynamics, oxygen need or liver status changes, because a previous refusal or acceptance may no longer reflect the current risk-benefit balance.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Progressive hypoxaemic failure

Hepatopulmonary vascular dilatation can cause severe exertional and resting hypoxaemia, reducing function and complicating procedural or transplant care.

Right-heart failure

Portopulmonary hypertension can cause oedema, syncope, low cardiac output and death as pulmonary resistance overwhelms right-ventricular reserve.

Transplant-related risk

Both syndromes materially affect transplant timing and perioperative safety, requiring joint liver, pulmonary-hypertension and anaesthetic assessment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

For HPS, track resting and exertional saturation, oxygen requirement, symptoms and periodic arterial oxygenation according to the transplant-centre plan.
For PoPH, monitor functional class, syncope, fluid state, right-ventricular function and treatment-specific blood tests within the designated pulmonary-hypertension service.
Repeat echocardiography or invasive haemodynamics at intervals determined by clinical change, drug escalation and transplant-policy requirements rather than a generic calendar.
Review adherence and adverse effects of oxygen or targeted therapy, including interactions created by declining hepatic function or newly prescribed medicines.
During transplant waiting, communicate any new admission, oxygen escalation, right-heart failure or treatment interruption promptly to both specialist teams.
After transplantation, continue cardiopulmonary follow-up until gas exchange or pulmonary haemodynamics have demonstrably resolved or stabilised.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Same portal setting

HPS and PoPH share portal hypertension as a context but move pulmonary vessels in opposite functional directions: dilatation and shunting versus obstructive vascular remodelling.

Bubble timing matters

Agitated saline is normally filtered by pulmonary capillaries; delayed systemic appearance reflects intrapulmonary transit, while immediate appearance raises an intracardiac route.

Echo estimates pressure

Tricuspid-regurgitant velocity and right-heart structure help select patients for catheterisation, but pressure estimation alone cannot measure pulmonary vascular resistance reliably.

High output mimics

Portal hypertension often increases cardiac output, which can elevate pulmonary arterial pressure without true PoPH; wedge pressure and resistance prevent this diagnostic error.

Transplant effects diverge

Transplantation treats the driver of HPS but may be dangerous in uncontrolled PoPH, so accurate phenotyping is a safety requirement rather than academic classification.

11Common pitfallsFrequent interpretation and management errors.

01
Equating any low oxygen saturation in cirrhosis with HPS without excluding parenchymal lung disease, fluid overload or pulmonary embolism.
02
Diagnosing PoPH from echocardiographic estimated pressure without confirmatory right-heart catheterisation.
03
Treating an increased pulmonary pressure in a high-output state as elevated pulmonary vascular resistance.
04
Using delayed bubbles to grade HPS severity instead of measuring arterial oxygenation.
05
Starting pulmonary arterial hypertension medicines outside a designated service despite hepatic interactions and transplant implications.
06
Applying an old memorised transplant cut-off rather than the current NHSBT selection policy and repeat specialist haemodynamics.