Excellent outcomes with liver transplantation in hepatopulmonary syndrome across pre-transplant PaO2 spectrum

Zakiyah Kadry; Eric Schaefer; Karen Krok; Alison Faust; Jonathan Gibson Stine; Ian Roy Schreibman; Dmitri Bezinover; Thomas Roberts Riley 3rd

doi:10.1016/j.jhepr.2021.100351

Excellent outcomes with liver transplantation in hepatopulmonary syndrome across pre-transplant PaO₂ spectrum

JHEP Rep. 2021 Aug 12;3(5):100351. doi: 10.1016/j.jhepr.2021.100351. eCollection 2021 Oct.

Authors

Zakiyah Kadry¹, Eric Schaefer², Karen Krok³, Alison Faust³, Jonathan Gibson Stine³, Ian Roy Schreibman³, Dmitri Bezinover⁴, Thomas Roberts Riley 3rd³

Affiliations

¹ Division of Transplantation, Department of Surgery, Penn State College of Medicine, Hershey, PA, USA.
² Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
³ Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA.
⁴ Department of Anesthesiology, Penn State College of Medicine, Hershey, PA, USA.

Abstract

Background & aims: Significantly worse survival has been reported in patients with hepatopulmonary syndrome (HPS) and partial pressure of arterial oxygen (PaO₂) <45 mmHg undergoing liver transplantation. Long-term pre- and post-transplant outcomes based on degree of hypoxaemia were re-examined.

Methods: A retrospective analysis of 1,152 HPS candidates listed with an approved HPS model for end-stage liver disease (MELD) exception was performed. A Fine and Gray competing risks model was utilised to evaluate pre-transplant outcomes for PaO₂ thresholds of <45, 45 to <60, and ≥60 mmHg. Post-transplant survival was analysed using the Kaplan-Meier method.

Results: Patients with a PaO₂ <45 mmHg were significantly more likely to undergo transplantation (hazard ratio [HR] 1.51; 95% CI 1.12-2.03), whereas patients with higher MELD scores had lower hazard of transplant (HR 0.80, 95% CI 0.67-0.95, p = 0.011) and higher hazard of pre-transplant death (HR 2.29, 95% CI 1.55-3.37, p <0.001). Post-transplantation, patients with a PaO₂ <45 mmHg had lower survival (p = 0.04) compared with patients with a PaO₂ ≥45 to <50 mmHg, with survival curves significantly different at 2.6 years (75% survival compared with 86%) and median survival of 11.5 and 14.1 years, respectively. Cardiac arrest was a more likely (p = 0.025) cause of death for these patients. Cardiac arrest incidence in patients who died with a PaO₂ >50 mmHg was 6.2%.

Conclusions: Patients with a PaO₂ <45 mmHg had a significantly higher rate of transplantation, and higher calculated MELD scores were associated with significantly higher pre-transplant mortality. Although post-transplant survival was lower in patients with a PaO₂ <45 mmHg, the median survival was 11.5 years, and survival curves only became significantly different at 2.6 years. This suggests that patients with HPS do benefit from transplantation up to 2-3 years post-transplant regardless of the severity of pre-transplant hypoxaemia.

Lay summary: A total of 1,152 patients with hepatopulmonary syndrome listed for liver transplant were analysed. Patients with a low PaO₂ <45 mmHg had a high likelihood of transplantation. If associated with advanced liver disease, the mortality risk was higher for patients with hepatopulmonary syndrome on the wait list. After liver transplantation, patients with a PaO₂ <45 mmHg had a lower survival, but this only became significant after 2.6 years, and the median survival was 11.5 years. This suggests that patients with hepatopulmonary syndrome do benefit from transplantation.

Keywords: CIF, cumulative incidence function; ECMO, extracorporeal membrane oxygenation; HPS, hepatopulmonary syndrome; HR, hazard ratio; Hepatopulmonary syndrome; Hypoxia; Liver transplantation; MELD, model for end-stage liver disease; NASH, non-alcoholic steatohepatitis; OPTN, Organ Procurement and Transplant Network; POPH, portopulmonary hypertension; PaO2, partial pressure of arterial oxygen; STAR, Standard Transplant Analysis and Research; UNOS, United Network for Organ Sharing.