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AIM: To study the presence of sustained low diffusing capacity (DLco) after liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS).METHODS: Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term (median,15 mo). HPS patients were also assessed at long-tem (median, 86 mo).RESULTS: Before LT, HPS patients showed lower PaO2 (71 ± 8 mmHg), higher AaPO2 (43 ± 10 mmHg) and lower DLCO (54% ± 9% predicted), due to a combination of moderate-to-severe ventilation-perfusion (VA/Q)imbalance, mild shunt and diffusion limitation, than nonHPS patients (94 ± 4 mmHg and 19 ± 3 mmHg, and 85% ± 3% predicted, respectively) (P ＜ 0.05 each).Seven non-HPS patients had also reduced DLCO (70% ±4% predicted).At mid- and long-term after LT, compared to preLT, HPS patients normalized PaO2 (91 ± 3 mmHg and 87 ± 5 mmHg), AaPO2 (14 ± 3 mmHg and 23 ± 5mmHg) and all VA/Q descriptors (P ＜ 0.05 each) without changes in DLCO (53% ± 8% and 56% ± 7% predicted,respectively). Post-LT DLCO in non-HPS patients with preLT low DLCO was unchanged (75% ± 6% predicted).CONCLUSION: While complete VA/Q resolution in HPS indicates a reversible functional disturbance, sustained low DLCO after LT also present in some non-HPS patients,points to persistence of sub-clinical liver-induced pulmonary vascular changes.