Liver transplants in HIV/HCV co-infection: study underlines importance of hepatitis C treatment

People with HIV and hepatitis C co-infection were significantly more likely to experience organ rejection than people with hepatitis C alone or HIV alone after undergoing a liver transplant, according to a review of 11 years' experience of liver transplantation in people with HIV and with hepatitis C virus (HCV) in the United States, published in advance online in the journal Clinical Infectious Diseases.

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 people with co-infection 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 in people with HIV. Although a study carried out by the United States National Institutes of Health (NIH) showed a somewhat lower rate of survival three years after transplantation and a higher rate of organ rejection in people with HIV and hepatitis C co-infection compared to people with hepatitis C alone (mono-infection), the majority of transplants in each group was successful. The success of transplantation in people with HIV who are not do not have hepatitis C co-infection has been unclear. Furthermore, data are lacking outside the clinical trial setting regarding the outcomes of transplants in people with co-infection, particularly at transplant centres which did not take part in the NIH trial.

Liver transplantation in people with hepatitis C is further complicated by the high risk of hepatitis C recurrence and subsequent rapid progression of fibrosis after 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 transplant is likely to continue to be necessary in 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 United States 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 HCV, 72 had HIV and 160 were had HIV and HCV co-infection. 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 co-infection group (P<0.001), while people with HIV were younger than the transplant recipients with HCV mono-infection 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 (p < 0.001).

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

Organ rejection and graft loss was significantly more common in the group with co-infection (44.8%) compared to the reference group (23.6%), and was also more frequent in transplant recipients with mono-infection (30.6% in people with HCV and 31.4% in people with HIV).

Univariable analysis found that HIV mono-infection was not associated with a significantly increased risk of death or organ rejection, whereas HCV mono-infection and HIV/HCV co-infection were (1.46 [95% confidence interval 1.41-1.52] and 2.62 [95% CI 2.06-3.33) respectively. Hepatitis C mono-infection and HIV/HCV co-infection were similarly associated with transplant rejection whereas HIV was not associated with rejection.

The authors conclude that any excess post-transplant risk for people with co-infection is related to hepatitis C, underlining the importance of treating the 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 for people with mono-infection and co-infection, with hepatitis C treatment after transplant. This option would broaden the donor pool, they suggest, making it more likely that people with hepatitis C with end-stage liver disease would receive the liver transplant they need.

Sawinski D 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. Clin Infect Dis, advance online publication, 16 June 2015.