Within the lifetime of many doctors in this province and within the professional lives of most, the medical community has witnessed a remarkable evolution—from demoralizing futility to success so common that it has become routine—of two very different areas of medicine: liver transplantation and the treatment of human immunodeficiency virus (HIV) infection. In the early 1960s, the first attempts at liver transplantation ended miserably with intra-operative or early postoperative mortality. By the 1970s, the major surgical obstacles had been overcome but graft loss from rejection remained a significant barrier. The development of cyclosporine[1] in the early 1980s resulted in reasonable post-transplant outcomes and the acceptance of liver transplantation as the final treatment for end-stage liver disease. Today, there is a wide array of efficacious immunosuppressive agents, as well as effective monitoring, prophylaxis, and treatment of serious opportunistic infections such as cytomegalovirus. In BC and the rest of Canada, patients and physicians alike can expect a 1-year survival of 85% and a 3-year survival between 75% and 80%. Similarly, the area of HIV treatment has evolved over a 20-year period. We have gone from merely coping with the manifestations of AIDS, the etiology of which was unknown at the time, to the remarkable era of highly active antiretroviral therapy (HAART), where patients with HIV infection live AIDS-free, with a good quality of life and undetectable HIV viremia. It was inevitable that these two remarkable advances in medical science would eventually intersect. Although liver transplantation in patients with HIV infection was not a feasible venture in the pre-HAART era,[2] the evidence in the HAART era, which Ms Paula Braitstein reviews in this issue of the BCMJ, suggests that transplantation in a selected group of HIV patients coinfected with hepatitis C virus (HCV) is viable with the potential for good long-term outcomes.[3] To date, no one in BC with HIV has received a transplant and only one patient coinfected with HIV and HCV has received a liver transplant in Canada. Despite this, the BC Transplant Society has been actively assessing HIV/HCV coinfected patients this past year and our protocols, developed in consultation with the HIV specialists, are based on the best available evidence in the transplant literature.

Aside from the specific issue of transplantation in coinfected patients, the reality of liver transplantation today is that there is a tragic disparity between the need for liver transplantation and donor availability. Over the years, many liver diseases that were originally absolute contraindications for transplantation have become primary indications. Examples include hepatitis B infection, which until the availability of lamivudine and hepatitis B immune globulin (HBIG) prophylaxis,[4] was associated with a high likelihood of graft re-infection and loss, and alcoholic cirrhosis in which a subgroup of patients may experience durable abstinence after successful rehabilitation.[5] When one adds systemic metabolic diseases, such as primary oxalosis,[6] for which liver replacement constitutes macrogene therapy, it is clear that while medical science continues to expand the indications for liver transplantation, the donor pool has remained essentially static. In blunt terms, more and more patients are competing for a scarce lifesaving resource. Given such desperate circumstances, the principles of utility must govern organ allocation, and those who do not have a reasonable likelihood of a long-term post-transplant survival must be excluded. Unfortunately, there is no place for a palliative liver transplant in today’s world.

The real human cost of today’s organ shortage, both from the perspective of society and from the perspective of the unfortunate individuals with end-stage liver disease and their families, is incalculable. Although part of the answer lies in increasing public awareness, developing living-related-donor programs, and exploring the potential of non-heart-beating donors, in truth, these measures will only ameliorate the problem of end-stage liver disease to a small degree. What is needed is a dedicated effort by both the medical community and society in general to reduce the number of people who will develop end-stage cirrhosis, thereby lessening the great imbalance between organ availability and need. This means not only providing effective treatment for those with chronic liver disease but also preventing vertical and horizontal transmission of viral infections and reducing injection drug and alcohol abuse to prevent acquired liver disease from occurring in the first place. Only by doing so will it be possible to prevent the tragedy of today’s organ shortage from becoming even greater tomorrow.

References

1. Starzl TE, Klintmalm GBG, Porter KA, et al. Liver transplantation with the use of cyclosporine A and prednisone. N Engl J Med 1981;305:266-269. PubMed Citation [9]
2. Tzakis AG, Cooper MH, Dummer JS, et al. Transplantation in HIV+ patients. Transplantation 1990;49:354-358. PubMed Abstract [10]
3. Neff GW, Bonham A, Tzakis AG, et al. Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease. Liver Transpl 2003;9:239-247. PubMed Abstract [11] Full Text [12]
4. Yoshida EM, Erb SR, Partovi N, et al. Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin. Liver Transpl Surg 1999;5:520-525. PubMed Abstract [13]
5. Gish RG, Lee AH, Keefe EB, et al. Liver transplantation for patients with alcoholism and end-stage liver disease. Am J Gastroenterol 1993;88:1337-1342. PubMed Abstract [14]
6. McDonald JC, Landreneau MD, Rohr MS, et al. Reversal by liver transplantation of the complications of primary hyperoxaluria as well as the metabolic defect. N Engl J Med 1989;321:1100-1103. PubMed Citation [15]

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Eric M. Yoshida, MD, MHSc, FRCPC, FACP

Dr Yoshida is an associate professor of medicine at the University of British Columbia and medical director of the Liver Transplant Program, the BC Transplant Society.