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Liver Transplants in HIV/HCV Coinfection: Study Underlines Importance of Hepatitis C Treatment

People with HIV and hepatitis C virus (HCV) coinfection were significantly more likely to experience organ rejection than people with either hepatitis C alone or HIV alone after undergoing a liver transplant, according to a review of 11 years of experience with liver transplantation in people with HIV and with hepatitis C in the U.S., published in the June 16 advance edition of the journal Clinical Infectious Diseases.

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The study investigators say that their findings underline the importance of treating hepatitis C either before or immediately after liver transplantation in order to improve outcomes, rather than assuming that coinfected patients will have poorer outcomes based on historical data.

Liver transplantation remains a relatively rare procedure among people living with HIV, due in part to concerns about poorer survival and higher rates of organ rejection. Although a study carried out by the U.S. National Institutes of Health (NIH) showed a somewhat lower rate of survival 3 years after transplantation and a higher rate of organ rejection in HIV/HCV coinfected people compared to people with HCV alone (monoinfection), the majority of transplants in each group were successful. The success of transplantation in people with HIV who are not coinfected with HCV has been unclear. Furthermore, data are lacking outside the clinical trial setting regarding the outcomes of transplants in coinfected people, particularly at transplant centers which did not take part in the NIH trial.

Liver transplantation in people with hepatitis C is further complicated by the high risk of HCV recurrence and subsequent rapid progression of fibrosis after a transplant, in the absence of highly effective treatment. Although more effective treatment is now becoming available that may cure hepatitis C in over 90% of people, before or after liver transplantation, liver transplants are likely to continue to be necessary for people with end-stage liver disease -- and hepatitis C is not the only cause of end-stage liver disease in people living with HIV.

Researchers at the University of Pennsylvania reviewed all liver transplants carried out in the U.S. between February 2002 and December 2013 -- a total of 43,987 transplant recipients with information on HIV and HCV serostatus. Of these people, 20,829 had hepatitis C, 72 had HIV, and 160 were HIV/HCV coinfected. A total of 22,926 people without HCV or HIV formed a reference group of transplant recipients.

African Americans were significantly more likely to be represented in the HIV and HIV/HCV coinfected groups, while people with HIV were younger than HCV monoinfected transplant recipients or those in the reference group. People with hepatitis C or HIV had significantly worse liver damage as measured by MELD score, and people with HIV were significantly more likely to have moderate to severe impairment of overall physical function than other groups.

The study found that 1- and 3-year survival was lowest in the coinfected group (75% and 47%, respectively) compared to the reference group (89% and 76%). 1-year survival was similar to the reference group in the HIV and the HCV monoinfected groups, but 3-year survival was lower (66% and 67%, respectively). Infections caused death more frequently in people with HIV and coinfected people.

Organ rejection and graft loss was significantly more common in the coinfected group (44.8%) compared to the reference group (23.6%), and was also more frequent in monoinfected transplant recipients (30.6% in HCV monoinfected and 31.4% in HIV monoinfected).

Univariate analysis found that HIV monoinfection was not associated with a significantly increased risk of death or organ rejection, whereas hepatitis C monoinfection and HIV/HCV coinfection were (hazard ratio 1.46 and 2.62, respectively). Hepatitis C monoinfection and HIV/HCV coinfection were similarly associated with transplant rejection, whereas HIV alone was not associated with rejection.

The authors concluded that any excess post-transplant risk for HIV/HCV coinfected people is related to hepatitis C, underling the importance of treating this infection.

The study authors say that their findings "argue for treatment of HCV infection either in the pre-transplant setting or immediately post-transplant." They argue that availability of new interferon-free combinations of direct-acting antivirals makes this feasible. Alternatively, they suggest, organs from donors with HCV could be transplanted to HCV monoinfected and HIV/HCV coinfected patients, with hepatitis C treatment after transplantation. This option would broaden the donor pool, making it more likely that people with hepatitis C with end-stage liver disease would receive the liver transplant they need.

6/26/15

Reference

D Sawinski, D Goldberg, E Blumberg, et al. Beyond the NIH Multicenter HIV Transplant Trial Experience: Outcomes of HIV+ liver transplant recipients compared to HCV+ or HIV+/HCV+ co-infected recipients in the United States. Clinical Infectious Diseases. June 16, 2015 (Epub ahead of print).