Hepatopulmonary syndrome: an emerging complication in HIV-hepatitis C virus co-infected patients

Abstract

Following the availability of highly active antiretroviral therapy (HAART), chronic liver disease now represents the major cause of morbidity and mortality for HIV-infected patients [1,2]. Among the wide spectrum of end-stage liver disease complications, hepatopulmonary syndrome (HPS) has not been described. We report a fatal case of HPS in a woman with HIV and Child–Pugh B cirrhosis due to hepatitis C virus (HCV). A 40-year-old psychotic woman, who had been followed up for a HIV/HCV co-infection over a period of 10 years, presented at our institution complaining of dyspnoea for 2 weeks. She had interrupted her antiretroviral therapy a year earlier. Her CD4 cell count was 22 cells/μl and her HIV-RNA viral load was 88 000 copies/ml. At presentation, with a temperature of 37°C and a respiratory rate of 25/min, she was cyanotic with clubbing of the fingers. She had hepatomegaly and stigmata of portal hypertension (spider angiomas, splenomegaly). Fine crackles could be heard over both lungs. Analysis (on room air) of arterial blood gases withdrawn while the patient was in a supine position showed hypoxemia (arterial partial pressure of oxygen (PaO2) was 50 mmHg and the arterial partial pressure of carbon dioxide (PaCO2) was 40 mmHg). The arterial blood gases worsened upon standing (PaO2, 42 mmHg; PaCO2, 39.3 mmHg) suggesting orthodeoxia. Blood testing showed the following values: haemoglobin, 12.6 g/dl and platelets, 40 000/μl. The serum transaminases were elevated; serum conjugated bilirubin was 30 μmol/l (normal range, < 17 μmol/l); albumin was low with a value 19 g/l (normal range, 35–45 g/l); and the prothrombin time was 51% (normal range, 75–100%). The serum brain natriuretic peptide level was normal. Microscopic examination and culture of sputum and broncho-alveolar lavage were negative for Pneumocystis jirovecii and other opportunistic pathogens. Chest radiographs showed bilateral basilar reticulonodular opacities and normal lung volumes. Pulmonary computerized tomographic angiography with contrast revealed no evidence of pulmonary emboli. Pulmonary function testing demonstrated a reduced carbon monoxide diffusion capacity. The presence of delayed contrast appearance in the left heart on contrast-enhanced echocardiocardiography confirmed the diagnosis of HPS. Continuous home oxygen therapy (6 l/min) and a new antiretroviral therapy regimen were initiated. After initial improvement of the dyspnoea, she died of a urinary sepsis 3 months later. Hepatopulmonary syndrome is defined as a triad of chronic liver diseases, hypoxemia < 70 mmHg and pulmonary vascular dilation [3]. The estimated prevalence of HPS in patients with chronic liver disease varies between 4 and 29% according to the heterogeneous criteria used for definition of the condition [3,4]. In a recent study among patients with hepatitis B or C infection, the reported prevalence was 1.1% [5]. Little data is available on HIV-infected patients as only two cases have previously been reported in the literature [6,7]. The mechanisms leading to pulmonary vasodilation are complex and multifactorial. There appears to be an imbalance between the vasodilating and vasoconstricting mediators (nitrogen monoxide and endothelin-1). Hypoxemia can be explained by anatomical shunting and a diffusion–perfusion abnormality [3,4,6]. HPS occurs mainly but not exclusively in cirrhotic patients with portal hypertension [3,4]. This increasingly frequent complication is characterized by a delayed diagnosis with a mean duration of respiratory symptoms of 4.8 years before diagnosis. The presence of hypoxemia associated with platypnea and orthodeoxia (decrease in PaO2 > 3 mmHg in the erect position) as in our observation is suggestive of clinically significant HPS [3,4,6,7]. When the diagnosis is suspected, analyses of arterial blood gases should be obtained in both erect and supine positions. Attention in daily practice should be drawn to the presence of basilar interstitial infiltrates on chest radiographs, mimicking interstitial lung diseases or opportunistic pulmonary infections. Moreover, a high-resolution computerized tomography scan of the chest is useful to rule out other causes of hypoxemia and confirm the vascular etiology (dilated lung vessels) of the opacities [8]. Contrast-enhanced echocardiography is the key diagnostic tool [3,4]. HPS represents a significant mortality risk factor (overall mortality of 41% at 3 years after onset of dyspnoea) among cirrhotic patients, even after transplantation [9]. The most relevant prognosis factor is severe hypoxemia, with a baseline PaO2 < 50 mmHg associated with high mortality [10]. Currently, there is no effective medical treatment (methylene blue, inhaled NO, garlic, norfloxacin) for HPS [4,6,9,11]. Orthotopic liver transplantation (OLT), an emerging practice in selected HIV/HCV co-infected patients, is the only efficient treatment since it can reverse oxygenation abnormalities [11–13]. No data is available yet in this group. Thus, HPS should be considered in every case of a HIV patient with associated liver disease, presenting with an unexplained dyspnoea and hypoxemia. Early detection of ‘subclinical HPS’ by systematic arterial blood gas measurements in HIV-associated liver disease improves the prognosis.