Refractory hepatic hydrothorax is associated with increased mortality with death occurring at lower MELD-Na compared to cirrhosis and refractory ascites

Background and Aims: Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized Model for End-stage Liver Disease (MELD) exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA). Approach and Results: This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (adjusted HR [aHR] 4.63, 95% CI 3.31–6.48) than RA overall and within all MELD-sodium (MELD-Na) strata (<10 aHR 4.08, 95% CI 2.30–7.24, 10–14.9 aHR 5.68, 95% CI 2.63–12.28, 15–24.9 aHR 4.14, 95% CI 2.34–7.34, ≥25 aHR 7.75, 95% CI 2.99–20.12). LRD was higher among participants requiring 1 (aHR 3.54, 95% CI 2.29–5.48), 2–3 (aHR 4.39, 95% CI 2.91–6.63), and ≥4 (aHR 7.89, 95% CI 4.82–12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p =0.002) but higher MELD 3.0 (27.85 vs. 22.48, p <0.0001). Conclusions: RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.