Every HIV/hepatitis C-coinfected patient who survived liver transplant at a hospital in Barcelona experienced a recurrence of hepatitis C, and only one patient had a virological response to the subsequent use of anti-hepatitis C therapy, according to a study published in Antiviral Therapy. The authors note, however, that all the surviving patients were engaged in their normal daily activities two years after liver transplantation and that anti-HIV therapy was safely and effectively reintroduced within weeks.
Liver disease has become a major cause of illness and death amongst HIV-positive individuals, with hepatitis C virus often being the cause. Progression to cirrhosis caused by hepatitis C is faster amongst patients with HIV, and they also have shorter survival once liver decompensation occurs. Several studies have shown that anti-hepatitis C therapy has only limited efficacy in HIV-positive patients, possibly due to toxic effects of some anti-HIV drugs on the liver, and interactions between anti-hepatitis C and antiretroviral drugs.
It is therefore anticipated that the number of HIV/hepatitis C virus-coinfected individuals requiring liver transplantation will increase. Although there is limited experience of liver transplantation in coinfected patients, the evidence to date suggests that survival, in the short-term at least, is just as good as that seen in hepatitis C monoinfected patients.
Many hepatitis C-infected patients experience a relapse of their infection after liver transplant. The optimal use of anti-hepatitis C therapy in transplant recipients experiencing a relapse of their hepatitis C is unknown. Investigators in Barcelona therefore reported their experiences of transplant outcome and treatment for hepatitis C recurrence in six patients between 2002 and 2004.
The patients had a median age of 42 years. Five were male and four had injecting drug use as their HIV/hepatitis C risk category. All were taking antiretroviral therapy with an undetectable viral load immediately before their liver transplant. Median CD4 cell count at this time was a little over 250 cells/mm3. Median hepatitis C serum RNA was almost 800,000 copies/ml in the patients prior to transplant. Two patients had taken unsuccessful anti-hepatitis C therapy. Hepatitis C genotype was 1a in three patients, 1b was present in one case, and 1a/1b in two patients.
One patient died of post-operative complications without a recurrence of hepatitis C virus 78 after liver transplantation. In the surviving five patients, anti-HIV therapy was reintroduced between four and 16 days after their operation, and in all individuals HIV viral load remained undetectable.
In all the surviving patients, hepatitis C virus had recurred within eleven weeks of transplant. Anti-hepatitis C therapy consisting of pegylated-interferon and ribavirin was initiated in all patients within two weeks of the recurrence being detected. Only one patient experienced a sustained virological response to this therapy. In the other patients, the median fall in hepatitis C RNA was 0.87 log10 at week twelve and 1.04 log10 at week 24.
Despite this poor rate of virological response, the investigators noted that all five patients were alive and had resumed their “normal active lives” two years after transplant. The patient who had achieved a sustained virological response still had an undetectable hepatitis C viral load at month 26. Of the other patients, two developed cirrhosis and two moderate chronic hepatitis.
In the light of these cases, the investigators make some recommendations for the management of HIV/hepatitis C-coinfected patients undergoing liver transplantation. First, they suggest that efforts should be made to diagnose a recurrence of hepatitis C as soon as possible. They believe that regular biopsies may be a useful tool. Second, the use of steroids and immunosuppressive therapy to prevent organ rejection should be tapered off slowly (over six months) and should not be stopped suddenly in the event of hepatitis C recurrence. Third, ribavirin should be used at the maximum possible dose. And, finally, longer-term anti-hepatitis C therapy, perhaps of indefinite duration, should be considered.
The investigators conclude, “newer strategies to prevent recurrence and increase response rates…are urgently needed.”