For people who still have the virus at the time of transplant their new liver almost invariably becomes re-infected with HCV. After the new liver has been implanted, virus levels drop for up to 23 hours, then began to rise, doubling every 2 days and are likely to reach pre-transplant levels within a few days of the procedure.
For people who have achieved SVR with interferon-based therapy just before transplantation the evidence is less clear. Most people will experience viral recurrence. This is caused by low level HCV genetic material that remains in the body usually in peripheral blood mononuclear cells (a type of white blood cell of the immune system) but which is undetectable using standard HCV tests. However, some studies indicate that pre-transplant treatment prevents HCV recurring in up to 25% of cases, which tends to show that it may well be worth having treatment before the operation, contrary to what has been the consensus up to now. The problem is that people awaiting transplants are typically seriously ill and often find the side effects of the treatment intolerable.
The rate of HCV C related disease progression and increases in viral load after a liver transplant are generally faster than in pre-transplant people with HCV. This is due to lowered resistance to fight the virus caused by the immunosuppressant drugs. As with HCV infection before transplant the outcome varies significantly between individuals. After a few years some people may have persistent viraemia with no significant liver damage, while others may have developed severe fibrosis.
Factors that may accelerate liver disease after transplantation
Whilst no single factor can predict who will progress to cirrhosis after transplantation the main risk factors are thought to be:
- High viral load at the time of transplantation or soon after surgery
There is a lot of evidence that the lower one HCV viral load at the time of transplantation, the less chance of recurrence and the greater chance of slower disease progression. So any significant reduction in HCV RNA is likely to prove beneficial.
- Infection with genotype 1 (especially 1b) or 4
- The age of the donor
In one study, the age of the donor seemed to make a significant difference to the progression of the disease in the person receiving the liver. 14% of people with HCV who received livers from donors younger than 30 years experienced recurrent post-transplant cirrhosis, compared with 45% of those who received livers from donors age 31-59, and 52% who received organs from donors older than 59. In the UK between 2001 and 2005 these are the ages of the liver donors:
| Liver transplants for patients with hepatitis C in the UK, 1 January 2001 - 31 December 2005, by donor age group |
| | | | | | |
| Donor Age Group | 2001 | 2002 | 2003 | 2004 | 2005 | TOTAL |
| | | | | | |
| <10 | 1 | 0 | 0 | 0 | 0 | 1 |
| 10-19 | 7 | 3 | 4 | 6 | 2 | 22 |
| 20-29 | 9 | 17 | 8 | 7 | 5 | 46 |
| 30-39 | 18 | 13 | 9 | 23 | 14 | 77 |
| 40-49 | 21 | 25 | 24 | 22 | 15 | 107 |
| 50-59 | 34 | 27 | 30 | 24 | 13 | 128 |
| 60 | 16 | 21 | 14 | 21 | 6 | 78 |
| | | | | | |
| TOTAL | 106 | 106 | 89 | 103 | 55 | 459 |
| | | | | | |
Figures supplied by
UK Transplant - Ischemic time
This is the amount of time that the liver is kept on ice without a supply of oxygen after removal from the donor. If there is an overly long time spent re-warming the liver before it is implanted in the recipient then there seems to be a higher risk of HCV infection recurring more severely. In one study, the risk of severe HCV disease at 1 year was 19% for a re-warming time of 30 minutes compared to 65% for 90 minutes, respectively. If this data is confirmed then it seems vital that that re-warming time should be kept to an absolute minimum.
- Female sex
Being female has also been linked to worse progression. It is not known why and seems strange as among non-transplant patients, women usually fare better than men.
Outcomes
It is clear, though, that there is a significant increase in the rate of disease progression in the first ten years after transplant compared to the first ten years of infections before a transplant.
One study has shown that approximately 25% of transplant recipients develop cirrhosis in the grafted liver within 5-10 years as compared with 10-40 years in non-transplant patients. Around 20% of people will develop cirrhosis within one year and a small proportion die of HCV related liver disease within five years. However, the overwhelming majority of people who survive the transplant will live without serious damage from HCV infection for five years.
