Incidence of acute rejection and patient survival in combined heart–liver transplantation

Abstract

Combined heart–liver transplantation (CHLT) is indicated for patients with concomitant end‐stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor‐specific antibodies (DSAs) compared with heart‐alone transplantation (HA). We conducted a retrospective analysis of 32 CHLT and 280 HA recipients in a single‐center experience. The primary outcome was incidence of ACR based on protocol and for‐cause myocardial biopsy. Rejection was graded by the International Society of Heart and Lung Transplantation guidelines with Grade 2R and higher considered significant. Secondary outcomes included the development of new DSAs, cardiac function, and patient and cardiac graft survival rates. Of CHLT patients, 9.7% had ACR compared with 45.3% of HA patients (p < 0.01). Mean pretransplant calculated panel reactive antibody (cPRA) levels were similar between groups (CHLT 9.4% vs. HA 9.5%; p = 0.97). Among patients who underwent testing, 26.9% of the CHLT and 16.7% of HA developed DSA (p = 0.19). Despite the difference in ACR, patient and cardiac graft survival rates were similar at 5 years (CHLT 82.1% vs. HA 80.9% [p = 0.73]; CHLT 82.1% vs. HA 80.9% [p = 0.73]). CHLT reduced the incidence of ACR in the cardiac allograft, suggesting that the liver offers immunoprotection against cellular mechanisms of rejection without significant impacts on patient and cardiac graft survival rates. CHLT did not reduce the incidence of de novo DSA, possibly portending similar long‐term survival among cardiac allografts in CHLT and HA.

Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions

“…Improved outcomes with concurrent liver transplantation are hypothesized to be related in part to immunoprotection from the liver allograft. Multiple recent single-center and UNOS database studies demonstrate decreased rates of cardiac allograft rejection after CHLT [24,27,28 ▪ ,29,30]. These findings may be related to the unique ability of the liver to bind and clear donor-specific HLA class I antibodies.…”

“…These findings may be related to the unique ability of the liver to bind and clear donor-specific HLA class I antibodies. In one cohort, no class I DSA was observed in patients after CHLT while present in nearly 10% of a comparative heart transplant-only cohort [28 ▪ ].…”

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study

“…In the entire cohort of Fontan patients, there has been no patient with clinically significant, biopsy proven acute cellular (2R or above) or antibody mediated rejection. It is believed that there is a protective affect that the liver confers to the heart through a number of mechanisms that promote immunotolerance, and this effect may be a factor in the long term outcomes in this group of patients 38–42 . Furthermore, there may be decreased incidence of graft coronary vasculopathy as well 43 .…”

“…It is believed that there is a protective affect that the liver confers to the heart through a number of mechanisms that promote immuno-tolerance, and this effect may be a factor in the long term outcomes in this group of patients. [38][39][40][41][42] Furthermore, there may be decreased incidence of graft coronary vasculopathy as well. 43 Interestingly, it has been noted that level of sensitization does not affect incidence of rejection in CHLT, likely due to this increased immunotolerance, and our study showed the degree of sensitization was not correlated with comorbidity or mortality in our cohort.…”