Reply

Abstract

Baccarani et al. from the University of Udine reported on their experience with transplantation for 26 hepatitis C virus (HCV)/human immunodeficiency virus (HIV)–coinfected patients. Overall, the 3-year patient survival rate of their cohort (79%) was higher than the rate reported for our US cohort (60%).1 The only factor that they found to predict survival was a pretransplant CD4 count nadir < 100/mm3, which was present in 3 of the recipients (12%) and may have reflected more advanced HIV disease or potentially more severe liver disease. The authors did not comment on the causes of death, so it is difficult to mechanistically determine how the low CD4 nadir was associated with a higher risk of death. In our US cohort, a pretransplant CD4 count < 200/mm3 and a CD4 count nadir < 100/mm3 were not significantly associated with graft loss in coinfected patients. More remarkable from our standpoint is the extremely low rate of acute rejection (only 6.5%) reported for this Italian cohort. This is dramatically different from the findings for our US cohort, for which the 90-day cumulative incidence of rejection was 22% (95% confidence interval = 15%-33%).1 In part, this likely reflects differences between the studies with respect to when and how immunosuppressive drugs were administrated, monitored, and adjusted. As Baccarani et al. emphasized, immunosuppressive drug levels were frequently monitored, especially in the first weeks after transplantation, presumably to facilitate dose adjustments to optimize calcineurin inhibitor (CNI) levels. Similarly to the Italian cohort, patients in the US cohort were monitored frequently (daily in the hospital and biweekly for months), and this led us to conclude that other factors may account for the striking differences in the incidence of rejection. Although appropriate trough levels of CNIs are achieved, patients on protease inhibitor–based antiretroviral regimens typically require a CNI dose reduction (to once daily or as infrequently as once a week with tacrolimus-based regimens). With the use of less-than-daily dosing, we speculate that the overall exposure to adequate CNI drug levels may be suboptimal despite an appropriate trough level. Additionally, it is possible that other viral copathogens or the antiretroviral regimen itself may influence the likelihood of rejection. We wholeheartedly concur with the authors' conclusions that patients with HCV/HIV infections should continue to be offered liver transplantation. HCV ranks as the number 1 indication for liver transplantation among HIV-infected persons in North America and Europe, and as persons with HIV live longer, decompensated cirrhosis and hepatocellular carcinoma will continue to rank high among the causes of morbidity and mortality in those coinfected with HCV. Although we hope that future HCV therapies will offer cures for infection and reduce the rates of cirrhosis in more patients in the years ahead, liver transplantation will remain an important lifesaving treatment option in the interim. Norah Terrault M.D., M.P.H.*, Burc Barin M.S. , Peter Stock M.D., Ph.D.*, * University of California San Francisco San Francisco, CA, EMMES Corporation Rockville, MD.