Rapid deterioration of HIV co-infected patients waiting for liver transplantation is not predicted by MELD

Abstract

HAART therapy has significantly decreased the morbidity and mortality associated with HIV infection and. as a result, people infected with HIV are no longer dying from progression of HIV to AIDS. Unfortunately, an increasing number of co-infected patients are dying from complications of liver failure. Liver disease is now the leading cause of death for HIVpositive patients co-infected with hepatitis C and a major cause of death for HIV/HBV co-infected patients.1 As a result of the increasing demand for liver transplantation inHIV-positive people and recognition of improved survival associated with HAART, a number of transplant centers are proceeding with liver transplantation in selected patients with well-controlled HIV. Multiple small studies in the era of HAART suggest that patient and graft survival rates are similar to those in HIV-negative recipients.2-10 It is on this background that Ragni et al.11 in this issue of Liver Transplantation demonstrate significantly shorter pretransplantation survival in HIV-positive patients listed for liver transplantation compared with HIV-negative subjects, despite equivalent Model for End-Stage Liver Disease (MELD) scores at the time of listing. Furthermore, the shortened pretransplantation survival times were primarily associated with death related to infection/sepsis in a subset of the HIV-positive candidates. Ragni et al.’s findings are highly relevant, in that this is the first documentation of a more rapid demise of the co-infected HIV liver transplant candidates that has been observed on waiting lists at an increasing number of transplant centers. The parameters that have proven to be predictive for poor outcome in the MELD system (INR, bilirubin, and creatinine) failed to predict the poorer outcome in the subset of HIV-positive patients who succumbed to infection/sepsis. CD4 counts at the time of listing were also unable to distinguish the subset of HIV-positive patients with poor outcomes. The higher incidence of sepsis-related death inHIV-positive people with liver insufficiency as compared to their HIV-negative counterparts on the liver transplant waiting list could be predicted on the basis of the multiple immunologic and metabolic insults present in the coinfected patient with liver insufficiency. In addition to the impaired detoxification capacity of the damaged liver, the co-infected patient is further compromised by the immune defects associated with HIV as well as the hepatotoxicity of several of the antiretroviral agents comprising HAART. Therefore, the documentation of increased sepsis/infections leading to decreased cumulative survival rates of HIV co-infected candidates on liver transplant waiting lists should come as no surprise. However, the issue of what can be done to improve the survival of the HIV co-infected liver transplant candidate remains unresolved. Ragni et al. stress the importance of early referral of the HIV co-infected patient, and the importance of this cannot be underestimated. There are multiple barriers that can delay the evaluation process leading to activation as an acceptable candidate, and Ragni et al.’s report makes it clear that this group of patients cannot afford these delays. It should be emphasized that these patients must meet the same standards as all liver transplant recipients, including a prolonged period of abstinence from alcohol and narcotics, sufficient rehabilitation, and demonstration of social support. Since HIV positivity is still perceived as a contraindication to transplantation by a significant percentage of the medical community, these issues have not been adequately dealt with by the time of referral. The problems with late referral are further exacerbated by the inherent complexity in caring for HIV/HBV and HIV/HCV coinfected patients. Many of these patients are disenfranchised from essential medical care as a result of poor insurance coverage. Even when appropriate medical consultation is obtained, the hepatologist will defer to the HIV specialist, the HIV specialist defers back to the