Predominantly right-sided pleural effusion occurring in patients with liver disease and no cardiorespiratory disease, often with minimal ascites. The ascitic fluid accumulates in the chest as a result of diaphragmatic defects. Occurs in 5–12% of patients with cirrhosis and portal hypertension. Spontaneous bacterial empyema can occur and is associated with mortality of 20%. Diuretics are rarely effective. The definitive treatment is liver transplantation.
Hepatopulmonary syndrome (HPS)
is the triad of:
• Chronic liver disease and portal hypertension
• Arteriovenous (AV) shunting in the lungs, predominantly at the bases and subsequent ventilation-perfusion abnormalities
• Arterial hypoxia.
It occurs in 4–29% of patients with chronic liver disease. Enhanced pulmonary production of NO is the key priming factor for pulmonary vasodilatation. Although levels of NO are increased in exhaled air, consistent with lung origin, levels normalize after liver transplantation. The mechanism is thought to be related to the release of vasoactive mediators from portal hypertension causing altered bowel perfusion, which, in turn, leads to pulmonary vascular dilatation, with decreased pulmonary vascular resistance (right-to-left shunt). Patients with cirrhosis who develop HPS have a worse prognosis.
is with progressive dyspnoea and cyanosis. Examination reveals clubbing and telangiectasia, with associated stigmata of chronic liver disease.
• Hypoxia on blood gases: <8.6kPa on air, at rest, and upright. Platypnoea and orthodeoxia are present, i.e. breathlessness and desaturation on sitting upright, caused by preferential perfusion of basal pulmonary vasculature where the AVMs will be, and AV shunting is therefore increased. Lying flat relieves this. These changes may be seen in other lung diseases but, in the presence of liver disease, is suggestive of HPS. Hypoxia is only partially corrected by 100% O2 due to the pulmonary shunting
• Contrast-enhanced echo is positive. Contrast/saline bubbles are injected peripherally and are normally seen only in the right heart and are then filtered by the pulmonary bed. In the presence of intrapulmonary shunts, these are seen in the left atrium within 3–6 cardiac cycles after opacification in the right atrium. (False positive results occur if right-to-left cardiac shunt present, which can be excluded during echo.) This is the most practical method of detecting pulmonary vascular dilatation. This qualitative method is more sensitive and less invasive than technetium-labelled albumin scan
• Pulmonary technetium-99 perfusion scan assesses the shunt fraction. Normally, the radiolabelled albumin is trapped in the pulmonary capillary bed. In the presence of intrapulmonary or cardiac shunts, there is significant uptake of radiolabelled albumin in the brain or spleen. A shunt index fraction of >20% indicates severe HPS (normal uptake <6%)
• CT chest is performed to rule out other pulmonary comorbid disease
• Single breath diffusion capacity for CO is consistently abnormal in HPS. This is not specific and may not normalize after transplant.
• O2 if PaO2 <8kPa
• Avoid vasodilators. There is minimal evidence for pharmacological intervention
• Mainstay of treatment is liver transplantation, which cures the condition in 80%. Hypoxia may take up to 14 months to improve. Severe hypoxia (PaO2 <6kPa) is associated with increased mortality post-transplant, as there is increased risk of hepatic ischaemia
• Transjugular intrahepatic portosystemic shunt (TIPS) is ineffective
• Coil embolization can be tried in selected cases with AV communications.
Porto-pulmonary hypertension (POPH)
is PAH occurring in association with liver cirrhosis and portal hypertension. It occurs in an estimated 2–5% of patients with cirrhosis and is present in around 16% of those referred for liver transplant. The mechanism is unclear but probably relates to a hyperdynamic circulation, high cardiac output, cytokine release, and possible PEs.
• Elevated PAP (>25mmHg at rest, >30mmHg during exercise)
• Increased pulmonary vascular resistance due to pulmonary vasoconstriction and obliterative vascular remodelling (>120dyn⋅s/cm5)
• Abnormal LV end diastolic/wedge pressure (<15mmHg)
• In the setting of portal hypertension (portal pressure >10mmHg).
Dyspnoea on exertion, possibly syncope, chest pain, fatigue, palpitations, haemoptysis, and orthopnoea. There may be signs of volume overload with raised JVP and pedal oedema. P2 may be loud, with pulmonary and tricuspid regurgitation, as well as stigmata of chronic liver disease. It is usually diagnosed 4–7y after the diagnosis of portal hypertension.
• Hypoxia on blood gases, but less so than in HPS. Worse on exertion
• CXR may be normal or show prominent pulmonary arteries and enlarged right heart
• ECG shows RVH, RBBB, RAD, and sinus tachycardia
• kCO may be decreased
• Echo is the main screening test and is diagnostic if the RV pressure is >50mmHg
• Exclude other causes of PHT
• Right heart catheterization (RHC) with vasodilator studies is performed
Options are the same as for patients with IPAH, with vasodilators, prostacyclin, and endothelin antagonists (see pp. [link]–[link]). Avoid β-blockers, so manage varices with banding. Anticoagulation is not advised due to the risk of variceal bleeding. LTOT if PaO2 <8kPa. If mean PAP <40mmHg, can undergo liver transplantation, which may reverse mild to moderate POPH, although symptoms may take weeks to months to resolve. Severe POPH is not reversed and is associated with significant intra- and post-operative morbidity and mortality. A few cases of heart-lung-liver transplants have been reported.
Porres-Aguilar M et al. Portopulmonary hypertension and hepatopulmonary syndrome: a clinician orientated overview. Eur Respir Rev 2012:21:223–33.Find this resource:
Rodriguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome—a liver-induced lung vascular disorder. N Engl J Med 2008;358:2378–87.Find this resource:
Pulmonary involvement tends to occur after the onset of the IBD but can predate it. Pulmonary involvement is found in up to a quarter of patients, but this is usually subclinical. Patients can develop a variety of clinical syndromes, including airway inflammation, subglottic stenosis, chronic bronchitis, bronchiectasis, and chronic bronchiolitis. Bronchoscopy may reveal inflammatory tissue within the large airway walls, which, on biopsy, shows mucosal ulceration, basal cell hyperplasia, basement membrane thickening, and submucosal inflammatory cell infiltration. IBD is also associated with the development of ILD, such as COP, pulmonary infiltrates with eosinophilia, or neutrophilic necrotic parenchymal nodules. Pulmonary involvement tends to be steroid-responsive. Inhaled steroids can be tried for chronic bronchitis, but oral or IV steroids may be required for worsening lung involvement. Note that drugs used in the treatment of IBD may also cause lung disease such as sulfasalazine (alveolitis), mesalazine, or infliximab (both: pulmonary infiltrates and eosinophilia; infliximab: reactivation of latent TB).
Pulmonary involvement is usually asymptomatic or may be associated with dry cough. Minimal interstitial change may be suggested by abnormal PFTs. Restrictive, obstructive, or reduced kCO defects may be seen. Usually normal CXR and CT. No specific treatment indicated.
May be associated with idiopathic lung fibrosis, causing restrictive defect. Also may be at increased risk of asthma, bird fancier’s lung, and haemosiderosis. Increased risk of lymphoma and malignancy in GI tract.
Acute pancreatitis is frequently associated with exudative pleural effusion. Raised amylase in the pleural fluid is suggestive (see p. [link]). ARDS may develop, which requires supportive care and mechanical ventilation (see p. [link]).