AASLD 2006: Liver Transplantation in HIV Positive Patients

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The Thomas E. Starzl Transplant Surgery State-of the-Art Lecture at this year’s American Association for the Study of Liver Diseases (AASLD) annual meeting was devoted to the outcomes following solid organ transplantation in HIV-infected recipients. The speaker, Peter G. Stock, MD, from the University of California at San Francisco, gave a very good update on the topic.

Liver transplantation in HIV-HCV coinfected patients is a recent indication that has become a reality thanks to the benefits conferred by HAART*. Given the increased morbidity and mortality due to liver disease in HIV-infected patients, there is a growing need for liver transplantation in this population.

Dr. Stock made the point that the state-of-the-art has improved in terms of prevention of post-transplant opportunistic infections (e.g., PCP, MAC, CMV, and candidiasis), and that it has been proven that certain immunosuppressive drugs (used to prevent rejection of the new organ) may also have anti-HIV effects. A challenge in the HIV-infected population is that poorer survival among candidates for liver transplants is unrelated to the severity of illness and is not predicted by MELD scores**.

Dr. Stock presented data on outcomes in 20 HIV-infected patients who underwent orthotopic liver transplantation (OLT). Survival of patient and graft was excellent among those with hepatitis B virus (HBV) infection (8 of 9 patients). However, 5 of 11 HIV-HCV coinfected patients died, due to recurrence of the HCV infection with fast fibrosis progression -- a problem that is also common among HCV monoinfected individuals.

Regarding complications, 3 patients experienced biliary strictures that were successfully managed. Kaposi’s sarcoma, a tumor associated with HHV-8, occurred in 1 patient who had received sirolimus as part of the immunosuppressive regimen. More importantly, human papillomavirus (HPV) infection appears to present a significant problem in HIV-infected transplant patients who already have accelerated cervical and/or anorectal disease, and who are at further risk of dysplasia progression after OLT. 

An unexpected finding was that spontaneous clearance of HCV was observed in 2 patients who experienced HCV recurrence after transplantation. Studies showed that an increased breadth of anti-HCV-specific cytotoxic T-lymphocyte immune responses in these patients over time. This phenomenon has not been reported in HCV monoinfected patients, which suggests that antiretroviral therapy and/or use of cyclosporin A might be involved.

Regarding the pharmacological management of HIV-positive transplant patients, Dr. Stock noted the potential for interactions between protease inhibitors (PIs) and immunosuppressive drugs. Thus, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the drugs of choice if a patient has NNRTI-susceptible HIV.

In summary, Dr. Stock highlighted that outcome for HIV-HBV coinfected patients undergoing OLT is very favorable. Recurrence of HCV infection may be a significant problem, although spontaneous HCV clearance can occur. HPV may pose a significant risk in HIV positive transplant patients and warrants regular monitoring (Pap smears), but HHV-8 seems to be less of a problem.

In addition, French researchers at AASLD presented an abstract on survival of HIV-infected OLT recipients. They compared the survival and the severity of recurrent HCV after liver transplantation in 23 HIV-HCV coinfected and 44 HCV monoinfected patients.

Coinfected patients were significantly younger (43 vs 53 years; P < 0.001) and had higher MELD scores (19.5 vs 15.1; P =0.004) than monoinfected patients. Two-year survival rates were 74% and 92% in coinfected and monoinfected patients, respectively (log-rank test, P = 0.07). By multivariate Cox analysis, only the MELD score was significantly associated with survival.

HCV viral load at 6 months was higher in coinfected than in monoinfected patients (6.8 vs 6.0 log; P = 0.03). Three coinfected patients developed severe acute hepatitis C. Two-year survival rates with graft fibrosis less than stage F3 were 36% in coinfected and 74% in monoinfected patients (P < 0.02).

The authors concluded that “survival is poorer and the recurrence of hepatitis C seems more severe after liver transplantation in HIV-HCV coinfected patients. New effective drugs against HCV, avoidance of drug toxicity, and prolonged anti-HCV therapies are mandatory to improve the results of this challenging indication of OLT.”

11/14/06

References

P Stock. Don't Judge a Book By Its Cover: The Unexpected Outcomes Following Solid Organ Transplantation in the HIV Positive Recipient. Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture. 57th AASLD. Boston, MA. October 27-31, 2006.

J. Duclos Vallee, C Feray, M Sebagh, and others. Survival and prognostic factors in a large cohort of HIV-HCV coinfected patients transplanted in a single centre. 57th AASLD. Boston, MA. October 27-31, 2006. Abstract 772.

*M Roland, and others. Liver transplantation in HIV-infected recipients. Seminars in Liver Disease. 26: 273-84. 2006.

**P Stock. Rapid deterioration of HIV co-infected patients waiting for liver transplantation is not predicted by MELD. Liver Transplantation 11(11): 1315-1317. November 2005.