Barriers to the successful treatment of liver disease by hepatocyte transplantation

Abstract

Management of patients with hepatic failure and liver-based metabolic disorders is complex and expensive. Hepatic failure results in impaired coagulation, altered consciousness and cerebral function, a heightened risk of multiple organ system failure, and sepsis [1]. Such manifold problems are only treatable today and for the foreseeable future by transplantation. In fact, whole or auxiliary partial liver transplantation is often the only available treatment option for severe, even if transient, hepatic failure. Patients with life-threatening liver-based metabolic disorders similarly require organ transplantation even though their metabolic diseases are typically the result of a single enzyme deficiency, and the liver otherwise functions normally. For all of the benefits it may confer, liver transplantation is not an ideal therapy, even for severe hepatic failure. More than 17,000 patients currently await liver transplantation in the United States, a number that seriously underestimates the number of patients that need treatment [2], as it has been estimated that more than a million patients could benefit from transplantation [3]. Unfortunately, use of whole liver transplantation to treat these disorders is limited by a severe shortage of donors and by the risks to the recipient associated with major surgery [4].

Fig. 1. Partial portal vein occlusion

Laboratory studies indicate that transient occlusion of the portal circulation can enhance donor hepatocyte engraftment by providing a proliferation signal to donor cells, with or without conditioning of the recipient liver by partial irradiation. Transient occlusion of the left portal venous system is shown, allowing transplantation into the right lobe of the liver. A 6 Fr compliant balloon is positioned in the left portal vein just beyond the bifurcation. It is inflated so as to occlude the left portal vein but allow transportal infusion of cells into the right lobe of the liver through the side port of the endovascular sheath.