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Treating the recurrence of HCV

When HCV has returned after a liver transplant its treatment is far harder to understand than it is before the transplant has taken place. It has not yet been agreed when it is best to treat people. Whether this should be before the operation, just after, or when the new liver begins to sustain damage has still not been agreed upon.

The side effects of treatment are usually more severe than for people with HCV who have not undergone transplantation. There has been some concern that anti-HCV therapy may be linked to an increased risk of people rejecting the new liver. Again, the extent of risk is not fully known. In one study, 8 out of 23 people with HCV who had transplants and were then treated with interferon showed evidence of liver rejection. Two people required a second transplant.

What is required is further study to determine the best immunosuppressive regimens for post-transplant patients with HCV. Whenever transplant recipients are treated for hepatitis C, care must be taken to minimize interactions between HCV therapy and immunosuppressive drugs.

  • Pre-emptive treatment prior to transplantation
    The aim of pre-emptive treatment is to stabilise or improve the functioning of the liver and reduce the likelihood of recurrent hepatitis C infection. Pre-emptive treatment carries significant risks of serious side-effects and the potential acceleration of liver deterioration. Data on pre-emptive treatment is scarce. One retrospective analysis of 26 cirrhotic transplant candidates treated with interferon, with or without ribavirin, reported no recurrent HCV among 6/6 individuals who achieved SVR prior to transplantation. But in each case adverse events were frequent and severe. More research is needed into the balance between risks and benefits before pre-emptive treatment is widely adopted as standard.
  • Starting treatment as soon as possible after transplantation
    HCV-RNA levels are usually at their lowest immediately after transplantation before rising to levels up to 20-fold higher than before transplantation. The goal of early post-transplant therapy is to stop the rapid viral replication and to limit liver damage. Again data on the effectiveness of early post-transplant therapy is limited. It is far from clear whether immediate pre-emptive therapy which would subject some people unnecessarily to adverse side effects is preferable to waiting until evidence of damage to the new liver becomes apparent. There is some evidence that early treatment helps reduce the risk of re-infection, but more research is required.
  • Delaying treatment until post-transplantation hepatitis has recurred
    One of the arguments for delaying treatment after transplants is that the patients are usually healthier overall and taking lower doses of immunosuppressive drugs. This is seen as enabling them to better tolerate HCV therapy. The treatment regime for people with recurrent HCV after transplant differs from those non-transplant patients with HCV. Dosages often have to be reduced, particularly ribavirin, because of the severity of side effects. Treatment is usually most effective amongst cases of mild recurrence of HCV infection, but the incidence of side effects is still high. In trials of peg-interferon and ribavirin amongst people with mild HCV recurrence SVR rates were over 60% in people who completed the trials. But the number of participants who had to abandon treatments was high. In one trial of 26 patients half of all patients could not finish the trial. Anaemia was the most common adverse reaction.

Anti-viral treatment is increasingly part of the strategy for post-transplantation, but the exact timing, duration and dosages are still being debated.