We read with great interest the article by Vibert et al. 1 regarding their experience with liver transplantation (LT) for hepatocellular carcinoma (HCC) in patients also infected with human immunodeficiency virus (HIV). It was very interesting to note that the authors reported the widest single-center experience in this field so far, focusing on an intent-to-treat analysis comparing HIV-positive and HIV-negative patients listed for LT. The main message from this experience is that HIV-positive patients are characterized by a higher dropout rate while on the waiting list, thus impairing the intent-to-treat analysis without a significant impact on the overall survival and HCC recurrence in comparison with the control group. However, in considering only the HIV-positive patients who underwent transplantation, three (19%) of 16 patients were outside the Milan criteria and one (6%) of 16 patients was outside the University of California San Francisco (UCSF) criteria. Immunosuppressive therapy was based on calcineurin inhibitors (cyclosporine or tacrolimus) in all patients. It is not clear to us why these patients, with a higher tumor burden, did not receive an mTOR (mammalian target of rapamycin) inhibitor–based immunosuppressive regimen. In vitro2, 3 as well as in vivo4, 5 studies have shown the strong antitumor effect of rapamycin. In addition, as we reported in a previous article,6 rapamycin is able to inhibit HIV progression, both reducing CCR5 gene expression on the surface of both lymphocytes and macrophages and interfering with the ability of differentiating monocytes to become susceptible targets for HIV infection. Furthermore, it is well-established that the HIV TAT protein, that is secreted by HIV infected cells and taken up by normal cells, drives hepatocarcinogenesis in patients with cirrhosis.7, 8 These are the reasons why rapamycin should be suggested as the immunosuppressive drug of choice in HIV-infected patients who have undergone LT for HCC, especially when pathological examination shows a tumour outside Milan or UCSF criteria.
Another question that arises from reading this interesting work is the CD4 T cell count in the group of HIV-infected patients who underwent LT. Two patients had a pre-LT CD4 count of 27/μL and 70/μL, respectively, with a very minimal survival (1 and 8 months, respectively). From June 2003 to January 2011, 27 patients underwent deceased donor LT at our center for end-stage liver disease, which was associated with HCC in 14 cases. Median CD4 T cell count in our experience was 295/μL (range 119-956/μL). A CD4 T cell count lower than 100/μL is an absolute contraindication according to our National Protocol for LT in HIV-positive patients; this is because of the high infection risk and the poor associated post-LT survival. 9 These concerns outline the necessity for an absolutely strict selection of HIV-positive patients to undergo LT because of the complexity in the management of these patients and the shortage of organs available for transplantation.