Objectives: The purpose of this retrospective study was to determine the rate of occurrence and features of pleural effusion in patients referred to our institution for liver transplant.

Materials and Methods: This study included 135 patients (43 women, 92 men) with a mean age of 40 years (range, 16-66 y). Patient characteristics such as history of pulmonary disease and types of respiratory symptoms were recorded. The chest radiographs of every study patient were examined.

Results: Of the 135 study patients, 16 (11.9%) had respiratory symptoms upon admission to the hospital, and 49 (36.3%) had abnormalities on their chest radiographs. The most common radiographic abnormality was elevated right hemidiaphragm in 32 patients (23.7%), followed by pleural effusion
in 22 (16.2%), atelectasis in 21 (15.5%), hilar enlargement in 18 (13.3%), and elevated left hemidiaphragm in 9 (6.6%). Seventeen of 22 patients (77.3%) had right pleural effusion, 4 (18.2%) had bilateral, and 1 (4.5%) had left pleural effusion. Of the 10 patients undergoing thoracentesis, 9 had transudates and 1 had an exudate.

Conclusions: Preoperative pleural effusion is a common problem in patients who are candidates for a liver transplant. Most of these patients have right transudative pleural effusion.

Key words : Pleural effusion, Liver transplant, Preoperative

Introduction

End-stage liver disease and its associated complications are leading causes of mortality and morbidity worldwide. The standard of care for life-saving treatment of patients with end-stage liver disease is liver transplant.^1-3 The rate of liver transplant has markedly increased, and studies have shown a 5-year survival rate of 80% after transplant.^4,5

The liver is a vital organ with major roles in homeostasis and metabolism and has important interactions with every organ. Pulmonary abnormalities, including pleural effusion, may arise in patients with chronic liver disease. Pleural effusion develops as a result of the passage of fluid that has accumulated in the peritoneal cavity through defects in the diaphragm into the pleural space.^6-8 The most commonly associated pulmonary symptoms include cough, shortness of breath, and chest pain. Pleural fluid is seen on the chest radiographs of 13% of patients with chronic liver disease, and occurs on the right side in 66% of these patients.⁹

The aim of this retrospective study was to determine the rate of occurrence and clinical features of pleural effusion seen on chest radiographs of patients who had been referred to our center for a liver transplant and who underwent preoperative evaluation by our pulmonary disease clinic.

Materials and Methods

The study included 135 patients with end-stage liver disease, aged between 16 and 66 years, who presented to the Transplantation Center of Baskent University Hospital, Ankara, Turkey, and who underwent evaluation by our pulmonary disease clinic between 2000 and 2013. Patient data including age, sex, smoking status, concomitant systemic and lung disease, and respiratory symptoms were collected from patient records.

The chest radiographs of every study patient were evaluated for radiological abnormalities. Patients with pleural effusion seen on chest radiography underwent thoracentesis, and a sample of pleural fluid was evaluated using the criteria of Light and associates to differentiate exudates from transudates. The fluid was considered an exudate if any of the following criteria applied: (a) the ratio of pleural fluid to serum protein greater than 0.5, (b) the ratio of pleural fluid to serum lactate dehydrogenase greater than 0.6, (c) pleural fluid lactate dehydrogenase greater than two thirds of the upper limit of the normal serum value. If one or more than one criteria is present, then pleural fluid is an exudate, and if none of them are present, then it is a transudate.10 Every pleural fluid sample was also evaluated for the presence of microorganisms.

All imaging studies undergone by each study patient, including chest radiography, abdominal ultrasonography, and abdominal computed tomography, were evaluated for the presence of ascites; and that information was recorded. The study was approved by the Ethical Review Committee of the institute. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 11.0, IBM Corporation, Armonk, NY, USA). Categorical variables are presented as numbers and percentages, and continuos variables as mean ± SD (standard deviation). The chi-square test was used for comparison between categorical variables. Statistical significance was defined by P < .05.

Results

Patient characteristics are summarized in Table 1. The mean age of the 135 study patients was 40.0 ± 14.7 years. There were 92 males (68.1%) and 43 females (31.9%). Sixty-one patients (45.2%) had a history of smoking (21.4 ± 16.3 pack years [range, 2 to 80]). Eleven patients (8.1%) had concomitant pulmonary disease, and 51 patients (37.8%) had concomitant systemic disease. There were 16 patients (11.9%) with respiratory symptoms. Cough was the most common symptom, occurring in 10 patients.

There were 49 patients (36.3%) with abnormal findings on chest radiography. The most common radiographic finding was elevated right diaphragm in 32 patients (23.7%). Pleural effusion was seen in 22 patients (16.3%), which was on the right in 17 patients (77.3%, n=22), bilateral in 4 (18.2%), and on the left in 1 patient (4.5%). Of 10 patients undergoing thoracentesis, 9 pleural fluid samples were transudates and 1 was an exudate. All of the samples were culture negative.

Other radiographic findings included atelectasis in 21 patients (15.5%), hilar enlargement in 18 (13.3%), and elevated left diaphragm in 9 (6.6%). Atelectasis involved the right lung in 15 patients (71.4%, n=21). The patients’ radiologic characteristics are summarized in Table 2.

Abnormal radiographic findings were seen in 29.7% of nonsmokers and 44.3% of smokers, which was not statistically significant (P = .08). There was also no statistical difference between the number of smokers and the number of nonsmokers with pleural effusion (P = .80).

Evaluation of patients with respect to concomitant pulmonary disease and abnormal radiographic findings showed no significant relation (P = 0.51). Pleural effusion was found in 31.5% of patients without respiratory symptoms and 55.6% of those with respiratory symptoms, which was not significant (P = .16), although pleural effusion was associated with increased coughing and dyspnea. Similarly, abnormal radiographic findings were found in 34.5% of patients without respiratory symptoms and 50.0% of those with respiratory symptoms, which was not significant (P = .225),

Ascites was found in 81.8% of patients with pleural effusion and in 36.6% of those without pleural effusion (P = .001). There was no statistically significant association between the number of patients with and without respiratory symptoms and the presence of ascites and with and without elevated right diaphragm and the presence of ascites (P = .83 and P = .16).

Discussion

Chronic liver disease is among the leading causes of death worldwide. Although liver transplant is performed successfully in many centers, thousands of people remain on waiting lists. Because the liver plays a major role in homeostasis and metabolism, chronic liver disease also is associated with concomitant failure of many organ systems including the respiratory system.11 Because of increases in the rate and severity of postoperative respiratory disorders in patients undergoing liver transplant, preoperative thoracic evaluation is now considered essential. Chest radiography is the most important diagnostic tools for evaluating these patients.¹²

Pleural effusion is a rare complication of end-stage liver disease, and resistance to treatment is an indication for liver transplant.¹³ Hepatic hydrothorax is defined as pleural effusion that develops in cirrhotic patients who do not have cardiac or pulmonary disease.¹⁴ Although hepatic hydrothorax is often associated with ascites, in some patients, it may develop in the absence of ascites.¹⁵ A 2012 study by Dinu and associates found that 90% of patients with hepatic hydrothorax also had ascites.¹⁶ Similarly, in our study, ascites was found in 81.8% of patients with pleural effusion, and the association was statistically significant (P = .001).

The main mechanism for pleural effusion is thought to be the passage of fluid accumulated in the peritoneal cavity into the pleural space through small defects in the tendinous portion of the diaphragm as a result of negative intrathoracic pressure. Diaphragmatic defects were demonstrated by Chen and associates in 1988, and their findings were subsequently supported by many other studies.^13,17 Pleural effusion may occur without any accumu-lation of fluid in the peritoneal cavity when the rate of ascites formation is equal to the rate of pleural reabsorption.¹⁸

Previous studies have reported that the prevalence of pleural effusion in patients with end-stage liver disease ranged from 5% to 10%.^19,20 Pleural effusion was found in 16.3% of our study patients, which is consistent with the literature. Cardenas and associates and Lazaridis and associates found pleural effusion involving the right lung in 85% of patients, whereas Reichen and associates found pleural effusion involving the right lung in 65% of patients.^13,21,22 In our study, 77.3% of patients had pleural effusion involving the right lung.

In patients with hepatic hydrothorax, dyspnea and cough are common symptoms, whereas chest pain is a rare, but nonspecific symptom. Only 16 of our patients (11.9%) had respiratory symptoms. Thoracentesis is recommended for patients who have liver disease and pleural effusion to rule out other causes or to alleviate respiratory symptoms. The pleural fluid from thoracentesis is usually a transudate, with characteristics similar to ascites.11 In our study, 9 of 10 patients undergoing thoracentesis had transudates.

One of the important cause of transudative pleural fluid is hepatic hydrothorax, and it regresses spontaneously with transplant. This retrospective study reported on the rate of occurrence and characteristics of pleural effusion in patients who were candidates for liver transplant.

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