Liver transplantation for hepatopulmonary syndrome: A systematic review and meta-analysis.

Background & Aims: Hepatopulmonary syndrome (HPS) is a severe pulmonary vascular complication of liver disease. Liver transplantation (LT) is the only definitive treatment, yet a contemporary synthesis of LT outcomes in HPS, alongside persisting uncertainties, is lacking. Methods: We conducted a systematic review and meta-analysis of 22 studies to evaluate HPS prevalence, post-LT survival, and HPS resolution. Results: Pooled HPS prevalence was 17.2% (11.6-24.7%, n = 1,171 studied patients) among patients with cirrhosis evaluated for LT, 26.1% (18.5-35.5%, n = 629) in patients with portal hypertension evaluated for LT and 21.6% (11.2-37.4%, n = 737) in LT recipients. Under current model for end-stage liver disease (MELD) exception policies, waitlist mortality was 13.1% (0.6-78.5%, n = 1,240 studied patients). Post-LT survival in patients with HPS was comparable to that in patients without HPS and aligned with international benchmarks. Pooled 1-year post-LT survival rates were 85.5% in prospective studies from the pre- and post-MELD era (n = 240 studied patients), 93.9% in the post-MELD era (n = 99), and 83.8% in registry-based studies (n = 800). Pooled estimates for 5-year post-LT survival rates were 85% (n = 144 studied patients), 92.9% (n = 99), and 76% (n = 739), respectively. Lower pre-LT PaO2 correlated with poorer post-LT survival, especially in very severe HPS. HPS resolved after LT in 90.1% (71.7-97.0%, n = 80 studied patients) of patients at 6 months, with complete resolution within 1 year in all patients assessed. Key gaps remain regarding the influence of underlying liver disease on HPS progression, the optimal timing of LT, and factors affecting post-LT recovery. Conclusions: LT offers substantial survival and clinical benefits for patients with HPS, with high rates of HPS resolution within a year. Patients with very severe HPS warrant closer monitoring, and further research is needed to address unresolved questions regarding disease trajectory and post-transplant outcomes. Impact and implications: This systematic review and meta-analysis shows that liver transplantation (LT) is an effective treatment for hepatopulmonary syndrome (HPS), resulting in high rates of syndrome resolution and post-transplant survival comparable to patients without HPS. These findings support the continued use of MELD exception policies and underscore the importance of timely referral for LT. While outcomes are generally favorable, patients with very severe HPS may experience worse post-transplant outcomes, highlighting the need for more tailored clinical management. A key unmet need remains in understanding the role of underlying liver disease severity in the natural history of HPS, as well as the optimal timing for LT and factors influencing post-transplant recovery.