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Risk Factors for Hepatic Hydrothorax in Cirrhosis Patients with Ascites – A Clinical Cohort Study

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Abstract

Background

The risk factors for hepatic hydrothorax are unknown.

Methods

We used data from three randomized trials of satavaptan treatment in patients with cirrhosis and ascites followed for up to 1 year. We excluded patients with previous hepatic hydrothorax or other causes for pleural effusion. The candidate risk factors were age, sex, heart rate, mean arterial pressure, diuretic-resistant ascites, a recurrent need for paracentesis, diabetes, hepatic encephalopathy, International Normalized Ratio, creatinine, bilirubin, albumin, sodium, platelet count, use of non-selective beta-blockers (NSBBs), spironolactone, furosemide, proton pump inhibitors, and insulin. We identified risk factors using a Fine and Gray regression model and backward selection. We reported subdistribution hazard ratios (sHR) for hepatic hydrothorax. Death without hepatic hydrothorax was a competing risk.

Results

Our study included 942 patients, of whom 41 developed hepatic hydrothorax and 65 died without having developed it. A recurrent need for paracentesis (sHR: 2.55, 95% CI: 1.28–5.08), bilirubin (sHR: 1.18 per 10 µmol/l increase, 95% CI: 1.09–1.28), diabetes (sHR: 2.49, 95% CI: 1.30–4.77) and non-use of non-selective beta-blockers (sHR: 2.27, 95% CI: 1.13–4.53) were risk factors for hepatic hydrothorax. Development of hepatic hydrothorax was associated with a high mortality-hazard ratio of 4.35 (95% CI: 2.76–6.97).

Conclusions

In patients with cirrhosis and ascites, risk factors for hepatic hydrothorax were a recurrent need for paracentesis, a high bilirubin, diabetes and non-use of NSBBs. Among these patients with cirrhosis and ascites, development of hepatic hydrothorax increased mortality fourfold.

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Acknowledgments

The authors thank Sanofi-Aventis R&D for providing access to the complete trial database from the satavaptan phase III trials in cirrhotic ascites and for permission to perform the analyses included in this publication.

Funding

This post-hoc analysis of the satavaptan trial data received no specific funding.

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Correspondence to Thomas Deleuran.

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Hugh Watson holds shares in Sanofi. No other disclosures.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Deleuran, T., Watson, H., Vilstrup, H. et al. Risk Factors for Hepatic Hydrothorax in Cirrhosis Patients with Ascites – A Clinical Cohort Study. Dig Dis Sci 67, 3395–3401 (2022). https://doi.org/10.1007/s10620-021-07134-8

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