Monitoring of Intrasplenic Hepatocyte Transplantation for Acute-on-Chronic Liver Failure: A Prospective Five-Year Follow-Up Study

Background

Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of chronic liver disease. Intrasplenic hepatocyte transplantation is increasingly recognized as a treatment for liver failure and genetic metabolic liver diseases. We describe our experience of intrasplenic hepatocyte transplantation in a small cohort of patients as bridge therapy or as an alternative to orthotopic liver transplantation (OLT).

Methods

Seven patients with ACLF with an expected survival of less than 8 weeks were enrolled into the study. The donor hepatocytes were collected from 2 healthy males and cryopreserved. Donor hepatocytes were transplanted into the spleen of recipients via catheterization of the femoral artery. All patients were followed up for 5 years or to death.

Results

A total of (4.2–6.0) × 10¹⁰ hepatocytes were harvested from the 2 donors' livers and their survival after recovery from the frozen stock was 63% ± 2.8% and 73.5% ± 3.2%, respectively. Following intrasplenic hepatocyte transplantation, 3 patients fully recovered from liver failure, 1 survived and subsequently underwent OLT, and the remaining 3 patients died between 2.5 and 12 months after intrasplenic hepatocyte transplantation. At month 48 post–intrasplenic hepatocyte transplantation, living hepatocyte signals were observed in the spleen using magnetic resonance imaging (MRI) with gadobenate dimeglumine (Gd-BOPTA).

Conclusions

Intrasplenic hepatocyte transplantation is a promising therapy for liver failure that may reduce mortality rates among patients with end-stage liver disease awaiting OLT. Conceivably, intrasplenic hepatocyte transplantation may be considered an alternative to OLT for patients with acute liver failure. MRI (Gd-BOPTA) is a useful tool for detecting living hepatocytes in the spleen after intrasplenic hepatocyte transplantation.