Major Challenges Limiting Liver Transplantation in the United States

Abstract

Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma.

Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration

“…These discoveries would revolutionize clinical management of large liver tumors and of liver transplantation. 5,6 Our laboratory contributed novel leads to such therapies by exposing the dramatic survival advantage afforded by hepatic overexpression of NF-κB-inhibitory and ubiquitin-editing protein, A20, 7,8 in mouse models of severe toxic or ischemic liver injuries, 9,10 and of extended (78%) and radical (87%) hepatectomy. 4 A20 confers this advantage by (i) limiting Received 29.9.14; revised 24.2.15; accepted 13.3.15; Edited by P Salomoni; published online 15.5.15…”

“…These discoveries would revolutionize clinical management of large liver tumors and of liver transplantation. 5,6 Our laboratory contributed novel leads to such therapies by exposing the dramatic survival advantage afforded by hepatic overexpression of NF-κB-inhibitory and ubiquitin-editing protein, A20, 7,8 in mouse models of severe toxic or ischemic liver injuries, 9,10 and of extended (78%) and radical (87%) hepatectomy. 4 A20 confers this advantage by (i) limiting inflammation through inhibition of NF-κB activation, (ii) protecting hepatocytes from apoptosis, 9 (iii) reducing oxidative stress by increasing peroxisome proliferator-activated receptoralpha (PPARα) expression, 10 (iv) promoting hepatocyte proliferation by decreasing cyclin-dependent kinase inhibitor (CDKI) p21, enhancing interleukin-6/signal transducer and activator of transcription-3 (IL-6/STAT3) regenerative signals, and (v) optimizing energy production by improving fatty acid (FA) metabolism.…”

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis

“…Although liver transplantation (Tx) is the gold standard of treatment for patients with decompensated liver cirrhosis, well-known challenges of Tx, such as a shortage of allografts, high cost of and complications due to surgery, and long-term immunosuppression, hinder the feasibility of this process (1). These challenges urge scientists and clinicians to perform new research to establish an alternative treatment, which every patient can benefit from and access easily.…”

Development of an improved rat model of dual graft liver transplantation with long-term survival

“…However, a severe shortage of cadaveric organ donors remains a major obstacle preventing the development of liver transplantation (Wertheim et al, 2011). Several innovative techniques such as split liver transplantation (SLT) and living donor liver transplantation (LDLT) have been developed to enlarge the relatively constant pool of organs (Strong et al, 1990;Hashikura et al, 1994;Yersiz et al, 2006).…”