Sex Differences in Liver Transplant Candidates With Portopulmonary Hypertension

Female candidates for liver transplant who have portopulmonary hypertension (POPH) have higher pulmonary vascular resistance (PVR), lower Model for End-Stage Liver Disease (MELD) scores, and are more likely to have autoimmune liver disease, compared with male candidates, according to study results published in CHEST.

Researchers conducted a retrospective cohort study in liver transplant candidates with POPH within the Organ Procurement Transplantation Network database.

Recognizing that POPH is a pulmonary vascular complication of advanced liver disease, investigators sought to describe sex differences in clinical characteristics, treatment response, pulmonary hemodynamics, and overall survival in patients with POPH. The link between sex and PVR, as well as between sex and overall survival, was evaluated via multivariate regression. All participants were stratified by age (<50 vs ≥50 years) to establish the ways in which age modifies the association between sex and hemodynamics, as well as between sex and overall survival. The primary study outcome was the effect of sex on baseline PVR.

A total of 190 adults (103 men and 87 women) were included in the study. Female participants had significantly lower MELD scores compared with male participants

(12.1±4.2 vs 13.8±4.9, respectively; P =.01). Women were also significantly more likely than men to have autoimmune hepatitis (14.9% vs 1.9%, respectively; P =.001).

Furthermore, female participants had significantly higher baseline PVR than male participants (610.6±366.6 dynes⋅s⋅cm^-5 vs 461.0±185.3 dynes⋅s⋅cm^-5, respectively;

P <.001), as well as significantly higher posttreatment PVR (244.6±119.5 dynes⋅s⋅cm^-5 vs 202.0±87.7 dynes⋅s⋅cm^-5, respectively; P =.008). Women also had significantly greater treatment responses (ΔPVR) compared with men (-359.3±381.9 dynes⋅s⋅cm^-5 vs -260.2±177.3 dynes⋅s⋅cm^-5, respectively; P =.03). Female sex continued to be significantly associated with higher baseline PVR in multivariate analysis (P =.008).

Rates of overall survival were similar between men and women (P >.05). When stratified according to age, however, female sex was independently associated with worse liver transplant waitlist survival in younger women (hazard ratio [HR], 6.61; 95% CI, 1.25-35.08; P =.03) but not in older women (HR, 1.08; 95% CI, 0.48-2.42; P =.86).

A major limitation of this study was the small patient population, in large part related to the fact that POPH is a relatively rare disease. Moreover, the patient cohort evaluated was a highly selected group of POPH liver transplant candidates with MELD exceptions.

The investigators concluded that additional research is warranted to explore potential mechanisms for these observed sex differences in POPH, including differential hormonal or genetic contributions.

Reference

DuBrock HM, Cartin-Ceba R, Channick RN, Kawut SM, Krowka MJ. Gender differences in portopulmonary hypertension. CHEST. Published online August 12, 2020. doi:10.1016/j.chest.2020.07.081