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Liver Transplants Successful in HIV+
Reported by Jules Levin
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This groundbreaking study reports findings that we have known for about a year by following closely the work of Michelle Roland based in SF and from hearing her updates. Many people had and still have doubts that HIV+ individuals could respond successfully to liver and kidney transplants. Many people felt and still do feel that HIV+ individuals should not be eligible to receive a transplant since available organs are few. The organ supply available is not increasing and the demand is increasing in the general population. At this time, the lists for liver transplants are long and HIV+ individuals are not prioritized. Some transplant surgeons are anxious about exposing themselves to the blood of an HIV+ person during the transplant procedure. However, there are doctors in the transplant research community who support HIV+ individuals having access. The University of Pittsburgh and Miami University are two academic centers that perform transplants for HIV+ individuals. They have been in the forefront and are supportive. There are also medical centers that shy away from offering this procedure to HIV+ individuals.
A patient should and can avoid being in a position to need a transplant. Obviously, these transplants are risky procedures and survival is not guaranteed. To avoid getting to the point of needing a liver transplant, everyone with HIV, particularly IVDUs, should be tested for Hepatitis C and B. Of course we need to increase our efforts to test people for HIV and to get them into care. If a person tests positive for Hepatitis they should get into care with a doctor knowledgable in HIV and hepatitis treatment. The timely monitoring of a patient's disease and proper care can help towards preventing the need for transplant.
Pegylated interferon and ribavirin is the standard of care combination treatment for individuals with HCV. Much research attention is dedicated to finding new drugs for HCV. Several HCV antivirals are in early development. Much progress is being paid in the treatment for Hepatitis B. 3TC (Epivir) and Adefovir can be successful in treating Hepatitis B. And there are a number of new drugs for HBV in various stages of development including entecovir, which has shown potent antiviral effect in early studies of HBV+ patients.
HIV-infected patients have been excluded from consideration for transplantation in the past because they were too sick in general to justify organ use. The immunosuppression required to perform transplant might accelerate HIV disease. But with the use of HAART, HIV+ persons are healthier, have improved immune systems, and have longer life expectancy. Michelle Roland, MD, presented her study results reviewing 53 cases of solid organ transplant (kidney & liver) in HIV-infected recipients in the HAART era in an oral session at Barcelona. Her prospective study evaluates the effect of immunosuppression on survival and HIV disease; drug interactions between PI/NNRTI and immunosuppressives. Many centers transplanted patients before this study started.
To be eligible for this study, patients had to have no history of opportunistic infections, CD4 > 200 for kidney transplant and >100 for liver; HIV viral load <50 for kidney, liver or if they were intolerant to ARTs in liver transplants it was ok if it was felt patients could be suppressed after the transplant when they would hopefully be more tolerant of ART. 1 patient was ineligible for study.
There were 45 eligible patients: 26 kidney and 19 liver recipients. 8 were ineligible for OI history, low CD4, HIV RNA >50. The average CD4 count was 441 (range: 200-1054) for kidney recipients and 280 (range: 103-973) for liver recipients. HIV RNA was on average <50 (range: 50-115,000).
RESULTS
The average follow-up of these patients has been 314 days so far (range: 3-1696). There have been 2 deaths among the 26 kidney transplants and 4 among the liver transplants.
Deaths in liver transplants were due to recurrent HCV at 15 months after transplant; rejection after PI discontinued after 1.5 years; post-operation pancreatitis; and unkown (>4.5 yrs).
Deaths in kidney transplants were due to ischemic bowel/ enterococcal sepsis at 6 months after transplant; chronic allograft nephropathy leading to staph sepsis 2+ months afterreturning to dialysis.
1 opportunistic complication occurred in a liver transplant: and 1 in a kidney transplant: CMV esophagitis, candida esophagitis.
Average CD4 count after transplant 436 (3-975) in kidney recipients and 218 in liver recipients (110-992). So on average patients appeared to maintain their CD4 count. HIV viral load was also <50 (<50-9500) for both kidney and liver transplant, again patients appeared to maintain viral load.
There was 1 liver re-transplantaion. Additional graft loss: 3 kidney (rejection x 2; thrombosis). Total rejection: 35% kidney + 21% liver.
Outcomes of Ineligible Subjects
One person had undiagnosed HIV (not mentioned above) and died of MAC & PML). One patient had altered MS and died of PML. Patients with history of OI (PCP +CMV, KS +CMV) had no recurrence at 19 and 6 months. CD4s remained relatively stable (76-195). HIV RNA >50 kidney transplants: <50 (1), <400 (2), >50 (1).
AUTHOR CONCLUSIONS
1. Patient Survival Similar in HIV+ to HIV- after 1 Year
--Roland reported that HIV+ patient survival in this study following liver and kidney transplants has so far been about equal to that seen in people without HIV. 92% of kidney recipients in this study have survived; 91% for 1 year (n=11). This compares to 94% survival rate for HIV negative persons as reported by UNOS, the organization keeping these statistics. For liver transplant recipients in this study 79% survived, 92% for 1 year (n=12). The UNOS survival rate for HIV negative persons was 87%.
2. Graft Survival Similar For HIV+ to HIV- After 1 Year
--85% of kidney recipients in the study, 71% 1 year (n=14) vs 89% for UNOS data in HIV negatives; 94% living.
--79% for liver recipients in this study, 83% for 1 year (n=12) vs UNOS HIV negatives 81%.
3. No significant HIV Disease Progression in Selected Patients
--stable CD4 counts and suppressed viral load
--only 2 opportunistic infections which could be due to HIV or immunosuppression
4. There is HIV Progression With Advanced Disease
Roland did not discuss the difference in response to transplant between
patients with HCV and HBV. It appears that HBV can be controlled well past
liver transplant. But patients with HCV don't do as well. It's my
understanding that 5% get severe disease and die in the first year. 25-30%
get cirrhosis by 5 years. Most patients have mild to moderate chronic
disease. It appears uncertain why. Perhaps its due to drug-drug interactions,
poor control of HCV after transplant or immunosuppressive drugs. It remains
unclear if using pegylated interferon plus ribavirin will improve outcomes.
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